Ignite Creation Date:
2024-05-06 @ 8:14 PM
Last Modification Date:
2024-10-26 @ 3:23 PM
Study NCT ID:
NCT06303076
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-03-12
First Post:
2024-03-04
Brief Title:
Tizanidine vs Zolpidem in Primary Insomnia A Randomized Trial
Sponsor:
Sultan Qaboos University
Organization:
Sultan Qaboos University
Study Overview
Official Title:
Efficacy of Tizanidine 01 mgKgHS Versus Zolpidem 10 mg HS in Primary Insomnia Double Blind Randomized Controlled Trial
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The studys primary objective is to evaluate the effectiveness of Tinazidine compared to Zolpidem in enhancing sleep quality with secondary objectives including the assessment of adverse effects safety profile and patient tolerance with each treatment The trial will be conducted as a double-blind RCT with participants randomly assigned to receive either Tinazidine 01 mgKgHS or Zolpidem 10 mg HS for 12 weeks Eligible participants aged 18-60 years diagnosed with primary insomnia as per DSM-5 criteria will be recruited from an outpatient sleep clinic affiliated with Al-Masara Hospital Data on sleep quality and side effects will be collected using the Sleep Pittsburgh Sleep Quality Index PSQI Clinical Global Impression CGI sleep diaries actigraphy polysomnography and regular clinical interview though OPD follow-up visits The primary outcome considered was the mean global PSQI score before and after the treatment The primary outcome will be measured four times baseline 4 weeks 8 weeks and 12 weeks We considered an attrition rate dropoutlost follow-up of 10 Therefore the sample size is 90 subjects 45 in each group Group comparisons for mean scores will be conducted using independent samples t-tests and within-group comparisons will be assessed using paired samples t-tests Changes in sleep quality over time between treatment groups will be evaluated using repeated measures ANOVA Associations between categorical variables will be examined using Chi-square tests including Fishers exact or Likelihood ratio tests as appropriate Statistical significance will be considered for p-values less than 005 All analyses will be performed using IBM SPSS Statistics Version 290 The findings of this study seek to elucidate the comparative efficacy and safety profiles of Tizanidine and Zolpidem in treating primary insomnia The study aims to offer insights into the effectiveness of Tizanidine versus Zolpidem in improving sleep quality among patients with primary insomnia Through the evaluation of efficacy adverse effects and safety profiles This study aims to inform clinicians and healthcare practitioners about the optimal treatment choices for individuals with primary insomnia
Detailed Description:
Efficacy of Tizanidine 01 mgKgHS versus Zolpidem 10 mg HS in Primary Insomnia Double Blind Randomized Controlled Trial
Literature review
Insomnia Prevalence and Impact
Around 10 of adults have an insomnia disorder while another 20 experience occasional insomnia symptoms 1 Women older adults and those facing socioeconomic challenges are more prone to insomnia Insomnia often persists over time with a 40 persistence rate over five years 1 Insomnia is a significant public health concern requiring individual clinical care and broad population-level interventions to improve sleep health 1
The Individual and Public Health Ramifications of Insomnia
On an individual level insomnia has significant repercussions on daily life including impaired daytime function emotional distress reduced productivity increased healthcare utilization and heightened accident risk 2 Along with physiological hyperarousal cardiometabolic morbidities such as hypertension and diabetes neurocognitive impairment such as short-term memory impairment and psychological impairment such as depression and anxiety 23 Additionally untreated insomnia tends not to improve over time 3
On a public level insomnia impacts various aspects of society It contributes to an increased economic burden through decreased work productivity and higher healthcare costs due to increased healthcare service utilization 4 Additionally insomnia heightens the risk of accidents including traffic accidents jeopardizing public safety 4 Its association with mental health disorders adds to the healthcare burden of managing these conditions while the increased risk of chronic medical diseases further strains healthcare systems 5 Given that the untreated economic costs of insomnia far exceed that of treated insomnia 4 efforts should be focused on developing clinical trials aimed at assessing the cost-benefit and cost-effectiveness of various insomnia therapies
Defining Primary Insomnia According to DSM-5 Criteria
Primary insomnia as defined in the DSM-5 criteria 6 refers to a sleep disorder characterized by difficulty initiating or maintaining sleep or experiencing non-restorative sleep for at least one month Individuals with primary insomnia often report significant distress or impairment in social occupational or other important areas of functioning due to their sleep difficulties The DSM-5 criteria further specify that insomnia is not better explained by another sleep disorder such as narcolepsy or circadian rhythm sleep disorder etc and not due to another mental disorder Additionally the diagnosis of primary insomnia requires that the sleep disturbance does not occur due to the physiological effect of a medical condition or substance use 6
Current FDA-Approved Medications for Insomnia
Current FDA-approved medications for insomnia include benzodiazepines such as Triazolam and Temazepam as well as non-benzodiazepines Z drug such as zolpidem and zaleplon Additionally melatonin agonist ramelteon tricyclic antidepressant doxepin and orexin antagonists such as suvorexant are also among the approved options for managing insomnia 7
Zolpidem was the first Z drug to be developed In studies investigating zolpidem adverse events that arose during treatment such as drowsiness nausea dizziness nightmares and agitation have led to the discontinuation of the zolpidem 7 Additionally some patients experienced anterograde amnesia 7 Moreover concerns about the frequent use of benzodiazepine for insomnia include the risk of dependence drug-seeking behavior and abuse in the context of inadequate medical supervision 8 Evaluating any new pharmacological treatments against conventional benzodiazepine and z-drugs intake is crucial as there is limited data on the benefit-to-risk ratio of such treatment strategies necessitating head-to-head trials
Therapeutic Applications of Tizanidine
Tizanidine a centrally acting alpha-2 agonist is commonly prescribed to manage spasticity induced by conditions such as multiple sclerosis stroke and spinal cord injury Beyond its labeled indications it finds off-label use in alleviating chronic neck and back pain as well as chronic migraines 9
Clinical Trials of Tizanidine in the Context of Insomnia
Tizanidine has shown promise in previous studies for its efficacy in sleep disturbances In a study where 24 subjects with Myofascial pain syndrome received tizanidine which was titrated up to 12 mg over 3 weeks and maintained for 2 weeks the study results showed Pain intensity and disability decreased significantly from baseline at weeks 3 and 5 and after washout P 001 Pressure threshold and sleep improved for all study periods P 001 The Sleep in this study was assessed via a visual analog scale VAS 10
In a randomized controlled clinical trial assessing the efficacy of adding either tizanidine or cyclobenzaprine in treating jaw pain 45 patients diagnosed with myofascial pain were randomly assigned to three groups a placebo group a tizanidine group 4 mg and a cyclobenzaprine group 10 mg Patients were assessed for changes in pain intensity using the modified Severity Symptoms Index and changes in sleep quality using the Pittsburgh Sleep Quality Index Results showed that all three groups experienced a reduction in pain symptoms and an improvement in sleep quality when comparing pretreatment and treatment scores 11
An open-label dose-titration study investigated the effectiveness and tolerability of tizanidine hydrochloride tablets in preventing chronic daily headaches The dosage was gradually increased from 2 mg at bedtime to a median daily dose of 14 mg mean 135 SD 43 range 4 to 20 divided over three doses per day by the fourth week of treatment Significant improvements were observed in overall headache status mood sleep quality of life P 00001 as well as sexual function P 0075 and the Beck Depression Inventory-II scores P 00073 Mild-to-moderate adverse events reported by 10 of patients included somnolence asthenia and dry mouth Three patients discontinued treatment due to somnolence dry mouth or constipation Additionally one patient experienced elevated liver enzymes which normalized after discontinuing the medication 12
Adverse Effects and Pharmacokinetic Considerations of Tizanidine
Adverse reactions associated with tizanidine include hypotension bradycardia or excessive sedation requiring gradual dose reduction or stopping therapy 9 Given its extensive hepatic metabolism tizanidines pharmacokinetics can be significantly altered in patients with hepatic impairment Thus special attention must be given to the dosing and monitoring of tizanidine in such individuals to mitigate risks 9 Similarly patients with renal impairment particularly those with a creatinine clearance below 25 mLmin require careful management when using tizanidine Initiation at lower doses along with close monitoring of therapeutic response is recommended 9 Any decision to prescribe tizanidine during pregnancy should involve a thorough risk-benefit assessment to ensure the safety of both the mother and the fetus Moreover considering tizanidines lipid-soluble nature potential transfer into breast milk raises concerns regarding its use during lactation 9 Smoking has been identified as a factor that reduces tizanidines plasma concentration and exposure as observed in studies such as Al-Ghazawi et al 13
Following oral administration of tizanidine the peak plasma concentrations occurred 1 hour after with a half-life of approximately 2 hours 14 The doses employed in the present study constitute an initial dose of 2 mg HS and it will be titrated up by 2 mg every 4 days as per response and tolerability up to a maximum dose of 01 mgkgHS administered before bedtime This proposed dose was found effective in a clinical trial assessing the effects of tizanidine for refractory sleep disturbance in disabled children with spastic quadriplegia The clinical trial included 21 children diagnosed with spastic quadriplegia and experiencing severe sleep disturbances All these children exhibited abnormalities in both falling asleep and staying asleep Tizanidine was administered at a dosage ranging from 01 to 02 mgkgday divided into two or three doses If daytime drowsiness was significant tizanidine administration was limited to just before bedtime Improvement in sleep induction andor maintenance was observed in 13 patients 619 Moreover the families of the patients expressed satisfaction with the treatment 15
The objective of this study was to compare in a double-blind design the subjective hypnotic efficacy and safety of Tizanidine 01 mgkgday and a Zolpidem 10 mg HS over 12 weeks in adult patients with primary insomnia
Study Objectives
Primary Objective
To evaluate the efficacy of Tizanidine compared to Zolpidem in improving sleep quality among patients with primary insomnia
Secondary Objectives
To assess the safety and side effect profile of Tizanidine
To compare patient tolerance and satisfaction between Tizanidine and Zolpidem treatments
Hypotheses
Main Hypothesis
Tizanidine is effective in the treatment of primary insomnia offering a better safety profile with fewer side effects
Secondary Hypotheses
Patients treated with Tizanidine will report fewer side effects compared to those treated with Zolpidem
Tizanidine will demonstrate higher patient tolerance and satisfaction in the treatment of primary insomnia
Methodology
Study Design
This study will be conducted as a double-blind randomized controlled trial Participants will be randomly assigned to receive either Tizanidine or Zolpidem for 12 weeks
The trial design is a parallel-group randomized controlled trial Participants will be randomly assigned to either one of the two treatment groups the Tizanidine group or the Zolpidem group This design allows for the comparison of the efficacy and safety of Tizanidine versus Zolpidem in the treatment of primary insomnia The allocation ratio will be 11 ensuring an equal distribution of participants between the two treatment arms
Trial setting
The data were collected at the outpatient sleep clinic affiliated with Al-Masarah Hospital Muscat Oman
Randomization
The method used to generate the random allocation sequence
The random allocation sequence was generated using a computerized random number generator
The type of randomization
Simple randomization was employed where each participant had an equal chance of being assigned to either the tizanidine group or the Zolpidem group
Study procedures
Study medications
Tizanidine Group
At all evenings and mornings during the treatment period at home participants will be asked to document the sleep diaries and to wear the actigraphy Sleep diaries are collected by the research assistant every week
Every 4 weeks the patients will be asked to complete the questionnaires Pittsburgh Sleep Quality Index PSQI and another self-report of suspected adverse drug reaction form
At baseline then in the 6th week and 12th week of the treatment the participants will be asked to attend the OPD for a clinical assessment by a specialist psychiatrist researcher The Clinical Global Impression CGI scale severity of illness global improvement and efficacy index assessed by the researcher
Throughout the study compliance was monitored by the research assistant calling the patients every other day in the morning
Safety was assessed by adverse events spontaneously reported by participants to the research assistant andor assessedobserved by the researcher during the clinical follow-up visit in 6th week and 12th week of the study and vital signs heart rate and blood pressure at baseline in 6th week and 12th week of the treatment
Polysomnography PSG at baseline and within one week of the end of the trial will be carried out
At the end of the study period a medical checkup by a medical officer will be carried out In the medical check-up a medical history will be carried out a physical examination including ECG and laboratory evaluation will be performed within 1 week of the end of the study treatment
Zolpidem Group
At all evenings and mornings during the treatment period at home participants will be asked to document the sleep diaries and to wear the actigraphy
Every 4 weeks the patients will be asked to complete the questionnaires Pittsburgh Sleep Quality Index PSQI and another self-report of suspected adverse drug reaction form
At baseline then in the 6th week and 12th week of the treatment the participants will be asked to attend the OPD for a clinical assessment by a specialist psychiatrist researcher The Clinical Global Impression CGI scale severity of illness global improvement and efficacy index assessed by the researcher
Throughout the study compliance was monitored by the research assistant calling the patients every other day in the morning
Safety was assessed by adverse events spontaneously reported by participants to the research assistant andor assessedobserved by the researcher during the clinical follow-up visit in 6th week and 12th week of the study and vital signs heart rate and blood pressure at baseline in 6th week and 12th week of the treatment
Polysomnography PSG at baseline and within one week of the end of the trial will be carried out
At the end of the study period a medical checkup by a medical officer will be carried out In the medical check-up a medical history will be carried out a physical examination including ECG and laboratory evaluation will be performed within 1 week of the end of the study treatment
Administration Both medications will be administered orally 30 minutes before bedtime
Outcome Measures
1 - Primary Outcome Improvement in sleep quality measured using the Pittsburgh Sleep Quality Index PSQI
2 - Secondary Outcomes Frequency and severity of side effects and patient satisfaction assessed through a self-report of suspected adverse drug reaction form
Data Collection Methods
Sleep diaries and actigraphy will be used to collect data on sleep patterns every morning and every night
Standardized questionnaires at the 4th week 8th week and 12th week of the study include the Pittsburgh Sleep Quality Index PSQI and a self-report of suspected adverse drug reaction form
Clinical follow-up visits during the 4th week of intervention 8th week of intervention and the 12th week of intervention will be scheduled to monitor progress and gather subjective assessments
Polysomnography PSG at baseline and within one week of the end of the trial will be carried out
Actigraphy
This is a method used to monitor activity and sleep-wake patterns over the study period It involves wearing a small wrist-worn device called an actigraph which contains sensors that detect movement and record activity levels continuously
Sleep diaries
These are self-reported records in which participants will be asked to track various aspects of their sleep-wake patterns over the study period individuals are typically asked to fill out sleep diaries first thing in the morning immediately upon waking up The diaries will involve recording information about bedtime wake-up time sleep onset latency time taken to fall asleep wake after sleep onset time spent awake during the sleep period and any nighttime awakenings
Polysomnography PSG
Polysomnography a diagnostic examination employed during sleep gathers physiological data through various sensors including electroencephalogram EEG electrooculogram EOG electromyogram EMG electrocardiogram ECG pulse oximetry airflow and respiratory effort
Pittsburgh Sleep Quality Index PSQI
The Pittsburgh Sleep Quality Index PSQI is a self-administered questionnaire designed to evaluate sleep quality within one month It comprises 19 specific items organized into seven components ultimately generating a single global score It is a widely used and validated instrument for assessing sleep quality in research and clinical settings It has been extensively validated in various populations and has demonstrated good psychometric properties 17 including reliability and validity in the Arabic version 18 This scale is copyrighted and is owned by the University of Pittsburgh and may be reprinted used without charge only for non-commercial research and educational purposes
Clinical Global Impression
Self-report of suspected adverse drug reaction form
Patients will be asked to fill out a pre-determined suspected adverse drug reaction form once a side-effect is suspected Moreover the research assistant will be utilizing a suspected side-effect form and will be conducting an interview another day to assess the patient for any suspected side-effects
Sample size
The sample size was estimated based on the anticipated difference effect size in the primary outcome between the two treatments Tizanidine Vs Zolpidem for the primary insomnia patients The primary outcome considered was the mean global PSQI score before and after the treatment We anticipated a medium effect size Cohens f 025 Repeated measures ANOVA for the primary outcome The type I error alpha was set at 5 and the power was set at 80 The primary outcome will be measured four times baseline 4 weeks 8 weeks and 12 weeks and the anticipated correlation among repeated outcome measures was 05 We also considered an attrition rate dropoutlost follow up of 10 Therefore the final sample size became 90 subjects 45 in each group The calculation was done in GPower version 3197
Data Analysis
Continuous variables will be presented as mean median standard deviation and interquartile range whereas categorical variables will be presented as frequency and percentage Comparison of mean scores between two independent groups will be assessed using the independent samples t-test whereas comparison of paired mean scores within the groups will be assessed using the paired samples t-test A repeated measures ANOVA will be applied to evaluate the changes over time in the sleep quality between the two treatment groups Association between two categorical variables will be assessed using a Chi-square test Fishers exactLikelihood ratio A P-value less than 005 will be considered statistically significant All the analysis will be carried out in IBM SPSS Statistics IBM Corp Released 2022 IBM SPSS Statistics for Windows Version 290 Armonk NY IBM Corp
Ethical Considerations
Informed Consent
In the informed consent process all potential participants will receive detailed information about the study A designated researcher from the study team will verbally explain the study in a language that is understandable to the participants This discussion will take place in the outpatient sleep clinic and will be witnessed by another researcher to ensure transparency and accuracy Any questions or concerns raised by the participants will be addressed at this time Suppose the participant agrees to participate in the study In that case they will be provided with a comprehensive information and consent sheet outlining the studys purpose procedures potential risks and benefits confidentiality measures and their rights as participants Subsequently the participant will be asked to sign the consent form Both the researcher who explained the study and the witnessing researcher will also sign the form to acknowledge the participants informed consent
Confidentiality
All data collected throughout the study will be anonymized to remove any personally identifiable information Additionally measures will be implemented to ensure the secure storage of data Access to study information will be restricted to authorized research personnel only and data will be stored on a password-protected computer
Literature review
Insomnia Prevalence and Impact
Around 10 of adults have an insomnia disorder while another 20 experience occasional insomnia symptoms 1 Women older adults and those facing socioeconomic challenges are more prone to insomnia Insomnia often persists over time with a 40 persistence rate over five years 1 Insomnia is a significant public health concern requiring individual clinical care and broad population-level interventions to improve sleep health 1
The Individual and Public Health Ramifications of Insomnia
On an individual level insomnia has significant repercussions on daily life including impaired daytime function emotional distress reduced productivity increased healthcare utilization and heightened accident risk 2 Along with physiological hyperarousal cardiometabolic morbidities such as hypertension and diabetes neurocognitive impairment such as short-term memory impairment and psychological impairment such as depression and anxiety 23 Additionally untreated insomnia tends not to improve over time 3
On a public level insomnia impacts various aspects of society It contributes to an increased economic burden through decreased work productivity and higher healthcare costs due to increased healthcare service utilization 4 Additionally insomnia heightens the risk of accidents including traffic accidents jeopardizing public safety 4 Its association with mental health disorders adds to the healthcare burden of managing these conditions while the increased risk of chronic medical diseases further strains healthcare systems 5 Given that the untreated economic costs of insomnia far exceed that of treated insomnia 4 efforts should be focused on developing clinical trials aimed at assessing the cost-benefit and cost-effectiveness of various insomnia therapies
Defining Primary Insomnia According to DSM-5 Criteria
Primary insomnia as defined in the DSM-5 criteria 6 refers to a sleep disorder characterized by difficulty initiating or maintaining sleep or experiencing non-restorative sleep for at least one month Individuals with primary insomnia often report significant distress or impairment in social occupational or other important areas of functioning due to their sleep difficulties The DSM-5 criteria further specify that insomnia is not better explained by another sleep disorder such as narcolepsy or circadian rhythm sleep disorder etc and not due to another mental disorder Additionally the diagnosis of primary insomnia requires that the sleep disturbance does not occur due to the physiological effect of a medical condition or substance use 6
Current FDA-Approved Medications for Insomnia
Current FDA-approved medications for insomnia include benzodiazepines such as Triazolam and Temazepam as well as non-benzodiazepines Z drug such as zolpidem and zaleplon Additionally melatonin agonist ramelteon tricyclic antidepressant doxepin and orexin antagonists such as suvorexant are also among the approved options for managing insomnia 7
Zolpidem was the first Z drug to be developed In studies investigating zolpidem adverse events that arose during treatment such as drowsiness nausea dizziness nightmares and agitation have led to the discontinuation of the zolpidem 7 Additionally some patients experienced anterograde amnesia 7 Moreover concerns about the frequent use of benzodiazepine for insomnia include the risk of dependence drug-seeking behavior and abuse in the context of inadequate medical supervision 8 Evaluating any new pharmacological treatments against conventional benzodiazepine and z-drugs intake is crucial as there is limited data on the benefit-to-risk ratio of such treatment strategies necessitating head-to-head trials
Therapeutic Applications of Tizanidine
Tizanidine a centrally acting alpha-2 agonist is commonly prescribed to manage spasticity induced by conditions such as multiple sclerosis stroke and spinal cord injury Beyond its labeled indications it finds off-label use in alleviating chronic neck and back pain as well as chronic migraines 9
Clinical Trials of Tizanidine in the Context of Insomnia
Tizanidine has shown promise in previous studies for its efficacy in sleep disturbances In a study where 24 subjects with Myofascial pain syndrome received tizanidine which was titrated up to 12 mg over 3 weeks and maintained for 2 weeks the study results showed Pain intensity and disability decreased significantly from baseline at weeks 3 and 5 and after washout P 001 Pressure threshold and sleep improved for all study periods P 001 The Sleep in this study was assessed via a visual analog scale VAS 10
In a randomized controlled clinical trial assessing the efficacy of adding either tizanidine or cyclobenzaprine in treating jaw pain 45 patients diagnosed with myofascial pain were randomly assigned to three groups a placebo group a tizanidine group 4 mg and a cyclobenzaprine group 10 mg Patients were assessed for changes in pain intensity using the modified Severity Symptoms Index and changes in sleep quality using the Pittsburgh Sleep Quality Index Results showed that all three groups experienced a reduction in pain symptoms and an improvement in sleep quality when comparing pretreatment and treatment scores 11
An open-label dose-titration study investigated the effectiveness and tolerability of tizanidine hydrochloride tablets in preventing chronic daily headaches The dosage was gradually increased from 2 mg at bedtime to a median daily dose of 14 mg mean 135 SD 43 range 4 to 20 divided over three doses per day by the fourth week of treatment Significant improvements were observed in overall headache status mood sleep quality of life P 00001 as well as sexual function P 0075 and the Beck Depression Inventory-II scores P 00073 Mild-to-moderate adverse events reported by 10 of patients included somnolence asthenia and dry mouth Three patients discontinued treatment due to somnolence dry mouth or constipation Additionally one patient experienced elevated liver enzymes which normalized after discontinuing the medication 12
Adverse Effects and Pharmacokinetic Considerations of Tizanidine
Adverse reactions associated with tizanidine include hypotension bradycardia or excessive sedation requiring gradual dose reduction or stopping therapy 9 Given its extensive hepatic metabolism tizanidines pharmacokinetics can be significantly altered in patients with hepatic impairment Thus special attention must be given to the dosing and monitoring of tizanidine in such individuals to mitigate risks 9 Similarly patients with renal impairment particularly those with a creatinine clearance below 25 mLmin require careful management when using tizanidine Initiation at lower doses along with close monitoring of therapeutic response is recommended 9 Any decision to prescribe tizanidine during pregnancy should involve a thorough risk-benefit assessment to ensure the safety of both the mother and the fetus Moreover considering tizanidines lipid-soluble nature potential transfer into breast milk raises concerns regarding its use during lactation 9 Smoking has been identified as a factor that reduces tizanidines plasma concentration and exposure as observed in studies such as Al-Ghazawi et al 13
Following oral administration of tizanidine the peak plasma concentrations occurred 1 hour after with a half-life of approximately 2 hours 14 The doses employed in the present study constitute an initial dose of 2 mg HS and it will be titrated up by 2 mg every 4 days as per response and tolerability up to a maximum dose of 01 mgkgHS administered before bedtime This proposed dose was found effective in a clinical trial assessing the effects of tizanidine for refractory sleep disturbance in disabled children with spastic quadriplegia The clinical trial included 21 children diagnosed with spastic quadriplegia and experiencing severe sleep disturbances All these children exhibited abnormalities in both falling asleep and staying asleep Tizanidine was administered at a dosage ranging from 01 to 02 mgkgday divided into two or three doses If daytime drowsiness was significant tizanidine administration was limited to just before bedtime Improvement in sleep induction andor maintenance was observed in 13 patients 619 Moreover the families of the patients expressed satisfaction with the treatment 15
The objective of this study was to compare in a double-blind design the subjective hypnotic efficacy and safety of Tizanidine 01 mgkgday and a Zolpidem 10 mg HS over 12 weeks in adult patients with primary insomnia
Study Objectives
Primary Objective
To evaluate the efficacy of Tizanidine compared to Zolpidem in improving sleep quality among patients with primary insomnia
Secondary Objectives
To assess the safety and side effect profile of Tizanidine
To compare patient tolerance and satisfaction between Tizanidine and Zolpidem treatments
Hypotheses
Main Hypothesis
Tizanidine is effective in the treatment of primary insomnia offering a better safety profile with fewer side effects
Secondary Hypotheses
Patients treated with Tizanidine will report fewer side effects compared to those treated with Zolpidem
Tizanidine will demonstrate higher patient tolerance and satisfaction in the treatment of primary insomnia
Methodology
Study Design
This study will be conducted as a double-blind randomized controlled trial Participants will be randomly assigned to receive either Tizanidine or Zolpidem for 12 weeks
The trial design is a parallel-group randomized controlled trial Participants will be randomly assigned to either one of the two treatment groups the Tizanidine group or the Zolpidem group This design allows for the comparison of the efficacy and safety of Tizanidine versus Zolpidem in the treatment of primary insomnia The allocation ratio will be 11 ensuring an equal distribution of participants between the two treatment arms
Trial setting
The data were collected at the outpatient sleep clinic affiliated with Al-Masarah Hospital Muscat Oman
Randomization
The method used to generate the random allocation sequence
The random allocation sequence was generated using a computerized random number generator
The type of randomization
Simple randomization was employed where each participant had an equal chance of being assigned to either the tizanidine group or the Zolpidem group
Study procedures
Study medications
Tizanidine Group
At all evenings and mornings during the treatment period at home participants will be asked to document the sleep diaries and to wear the actigraphy Sleep diaries are collected by the research assistant every week
Every 4 weeks the patients will be asked to complete the questionnaires Pittsburgh Sleep Quality Index PSQI and another self-report of suspected adverse drug reaction form
At baseline then in the 6th week and 12th week of the treatment the participants will be asked to attend the OPD for a clinical assessment by a specialist psychiatrist researcher The Clinical Global Impression CGI scale severity of illness global improvement and efficacy index assessed by the researcher
Throughout the study compliance was monitored by the research assistant calling the patients every other day in the morning
Safety was assessed by adverse events spontaneously reported by participants to the research assistant andor assessedobserved by the researcher during the clinical follow-up visit in 6th week and 12th week of the study and vital signs heart rate and blood pressure at baseline in 6th week and 12th week of the treatment
Polysomnography PSG at baseline and within one week of the end of the trial will be carried out
At the end of the study period a medical checkup by a medical officer will be carried out In the medical check-up a medical history will be carried out a physical examination including ECG and laboratory evaluation will be performed within 1 week of the end of the study treatment
Zolpidem Group
At all evenings and mornings during the treatment period at home participants will be asked to document the sleep diaries and to wear the actigraphy
Every 4 weeks the patients will be asked to complete the questionnaires Pittsburgh Sleep Quality Index PSQI and another self-report of suspected adverse drug reaction form
At baseline then in the 6th week and 12th week of the treatment the participants will be asked to attend the OPD for a clinical assessment by a specialist psychiatrist researcher The Clinical Global Impression CGI scale severity of illness global improvement and efficacy index assessed by the researcher
Throughout the study compliance was monitored by the research assistant calling the patients every other day in the morning
Safety was assessed by adverse events spontaneously reported by participants to the research assistant andor assessedobserved by the researcher during the clinical follow-up visit in 6th week and 12th week of the study and vital signs heart rate and blood pressure at baseline in 6th week and 12th week of the treatment
Polysomnography PSG at baseline and within one week of the end of the trial will be carried out
At the end of the study period a medical checkup by a medical officer will be carried out In the medical check-up a medical history will be carried out a physical examination including ECG and laboratory evaluation will be performed within 1 week of the end of the study treatment
Administration Both medications will be administered orally 30 minutes before bedtime
Outcome Measures
1 - Primary Outcome Improvement in sleep quality measured using the Pittsburgh Sleep Quality Index PSQI
2 - Secondary Outcomes Frequency and severity of side effects and patient satisfaction assessed through a self-report of suspected adverse drug reaction form
Data Collection Methods
Sleep diaries and actigraphy will be used to collect data on sleep patterns every morning and every night
Standardized questionnaires at the 4th week 8th week and 12th week of the study include the Pittsburgh Sleep Quality Index PSQI and a self-report of suspected adverse drug reaction form
Clinical follow-up visits during the 4th week of intervention 8th week of intervention and the 12th week of intervention will be scheduled to monitor progress and gather subjective assessments
Polysomnography PSG at baseline and within one week of the end of the trial will be carried out
Actigraphy
This is a method used to monitor activity and sleep-wake patterns over the study period It involves wearing a small wrist-worn device called an actigraph which contains sensors that detect movement and record activity levels continuously
Sleep diaries
These are self-reported records in which participants will be asked to track various aspects of their sleep-wake patterns over the study period individuals are typically asked to fill out sleep diaries first thing in the morning immediately upon waking up The diaries will involve recording information about bedtime wake-up time sleep onset latency time taken to fall asleep wake after sleep onset time spent awake during the sleep period and any nighttime awakenings
Polysomnography PSG
Polysomnography a diagnostic examination employed during sleep gathers physiological data through various sensors including electroencephalogram EEG electrooculogram EOG electromyogram EMG electrocardiogram ECG pulse oximetry airflow and respiratory effort
Pittsburgh Sleep Quality Index PSQI
The Pittsburgh Sleep Quality Index PSQI is a self-administered questionnaire designed to evaluate sleep quality within one month It comprises 19 specific items organized into seven components ultimately generating a single global score It is a widely used and validated instrument for assessing sleep quality in research and clinical settings It has been extensively validated in various populations and has demonstrated good psychometric properties 17 including reliability and validity in the Arabic version 18 This scale is copyrighted and is owned by the University of Pittsburgh and may be reprinted used without charge only for non-commercial research and educational purposes
Clinical Global Impression
Self-report of suspected adverse drug reaction form
Patients will be asked to fill out a pre-determined suspected adverse drug reaction form once a side-effect is suspected Moreover the research assistant will be utilizing a suspected side-effect form and will be conducting an interview another day to assess the patient for any suspected side-effects
Sample size
The sample size was estimated based on the anticipated difference effect size in the primary outcome between the two treatments Tizanidine Vs Zolpidem for the primary insomnia patients The primary outcome considered was the mean global PSQI score before and after the treatment We anticipated a medium effect size Cohens f 025 Repeated measures ANOVA for the primary outcome The type I error alpha was set at 5 and the power was set at 80 The primary outcome will be measured four times baseline 4 weeks 8 weeks and 12 weeks and the anticipated correlation among repeated outcome measures was 05 We also considered an attrition rate dropoutlost follow up of 10 Therefore the final sample size became 90 subjects 45 in each group The calculation was done in GPower version 3197
Data Analysis
Continuous variables will be presented as mean median standard deviation and interquartile range whereas categorical variables will be presented as frequency and percentage Comparison of mean scores between two independent groups will be assessed using the independent samples t-test whereas comparison of paired mean scores within the groups will be assessed using the paired samples t-test A repeated measures ANOVA will be applied to evaluate the changes over time in the sleep quality between the two treatment groups Association between two categorical variables will be assessed using a Chi-square test Fishers exactLikelihood ratio A P-value less than 005 will be considered statistically significant All the analysis will be carried out in IBM SPSS Statistics IBM Corp Released 2022 IBM SPSS Statistics for Windows Version 290 Armonk NY IBM Corp
Ethical Considerations
Informed Consent
In the informed consent process all potential participants will receive detailed information about the study A designated researcher from the study team will verbally explain the study in a language that is understandable to the participants This discussion will take place in the outpatient sleep clinic and will be witnessed by another researcher to ensure transparency and accuracy Any questions or concerns raised by the participants will be addressed at this time Suppose the participant agrees to participate in the study In that case they will be provided with a comprehensive information and consent sheet outlining the studys purpose procedures potential risks and benefits confidentiality measures and their rights as participants Subsequently the participant will be asked to sign the consent form Both the researcher who explained the study and the witnessing researcher will also sign the form to acknowledge the participants informed consent
Confidentiality
All data collected throughout the study will be anonymized to remove any personally identifiable information Additionally measures will be implemented to ensure the secure storage of data Access to study information will be restricted to authorized research personnel only and data will be stored on a password-protected computer
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None