Ignite Creation Date:
2024-05-05 @ 4:38 PM
Last Modification Date:
2024-10-26 @ 9:22 AM
Study NCT ID:
NCT00282061
Status:
UNKNOWN
Last Update Posted:
2006-12-15
First Post:
2006-01-24
Brief Title:
Synchronization and Desynchronization Between Circadian Rhythms in Patients With Delayed Sleep Phase Syndrome DSPS
Sponsor:
Sheba Medical Center
Organization:
Sheba Medical Center
Study Overview
Official Title:
None
Status:
UNKNOWN
Status Verified Date:
2006-01
Last Known Status:
RECRUITING
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:
This studys first aim is to widen the knowledge of the characteristics of delayed sleep phase disorder DSPS by focusing on the circadian rhythms of appetite regulation factors and their phase relations to the cycles of sleep-wake melatonin cortisol and body temperature This studys second aim is to assess the influence of forced morning awakening as a daily struggle faced by DSPS patients upon the synchronization of these variables in DSPS patients The investigators hypothesize that the chronic incompatibility between the endogenous sleep-wake rhythm of the DSPS patients and the morning wakefulness as a social demand may impair the synchronization between the different rhythms as findings indicate in normal subjects under jet lag And finally the third aim of the study is to assess the influence of successful treatment with melatonin upon the phase locations of circadian rhythms of studied measures and the synchronization between them These measures will be assessed in a controlled study for 36 hours sampled every 2 hours under three distinct experimental conditions first under free sleep-wake conditions ad-libitum bedtime and arousal second under restricted sleep-wake conditions enforced morning wake-up and finally after 12 weeks of melatonin treatment
Detailed Description:
Method
Subjects
A total of 20 subjects 10 diagnosed as DSPS patients and 10 matched healthy controls with a proven normal sleep-wake cycle
Exclusion criteria for the recruitment would be body mass index BMI higher than 28 or lower than 22 shift-work or chronic disease and chronic medication use
Procedure
Experiment 1- A comparison between 10 normal rhythm and 10 DSPS subjects under restricted sleep-wake schedule
Stage 1 10 day actigraphic monitoring under restricted sleep schedule using alarm clocks DSPS patients will be awakened at 700 am and control subjects will be awakened at 300 am
Stage 2 A 36 hour monitoring of the following measures body temperature melatonin cortisol Ghrelin subjective hunger sensation and eating behavior The subjects will be provided with ad-libitum food and will be instructed to eat whatever they like whenever they feel hungry
Experiment 2- A comparison between 10 normal rhythm and 10 DSPS subjects under ad-libitum sleep conditions
Stage 1 A 10 day actigraphic monitoring under ad-libitum sleep schedule Patients will be instructed to go to sleep whenever they feel tired and avoid any means of unnatural awakening
Stage 2 similar to experiment 1
Experiment 3- Examination of DSPS patients under melatonin administration and ad libitum sleep after 12 weeks of treatment
Stage 1 A 10 day actigraphic monitoring under ad-libitum sleep schedule Patients will be instructed to go to sleep whenever they feel tired and avoid any means of unnatural awakening Melatonin will be taken according to the medical instruction usually at 2200
Stage 2 similar to experiment 1
Measurements
Subjective hunger sensation will be measured with Visual Analogue Scale ratings for appetite assessment Flint et al 2000 Oh et al 2002 Parker et al 2004
Timing of meals and eating behavior will be recorded by the experimenter during the 36-hr monitoring
Sleep-wake rhythm normal or DSPS will be determined using the Actiwatch wrist activity monitoring system Actiwatch Cambridge Neurotechnology LTD
Plasma levels of Ghrelin will be sampled every 2 hours for 36 hours An intravenous catheter will be placed on the subjects arm 30 minutes prior to the first blood sampling Blood samples will be collected with chilled Vacutainer EDTA tubes and immediately centrifuged Plasma Ghrelin will be measured using commercial radioimmunoassay RIA- Phoenix Pharmaceuticals
Salivary levels of Melatonin and Cortisol Saliva will be collected by placing wool swab of plain Salivettes Sarstedt Disposable Products Regency Park Adelaide into the mouths of the subjects with chewing for 5 min Saliva samples will be taken at a total of 18 time points over a 36-h period for each subject The samples will be kept in Salivette tubes in the refrigerator at 4 ºC until the end of each 24-h period The Salivette tubes will be centrifuged for 15 min at 3000 g and the samples frozen at -20 ºC until assayed
Melatonin treatment Subjects with DSPS in the treatment group will be treated with melatonin according to a standard protocol for 3 months before the experiment
Oral temperature will be measured using standard medical mercury thermometer placed under the tongue for 3 minutes at a total of 18 time points over a 36-h period right after the saliva sample collection
Analysis Assays of Melatonin and cortisol Melatonin in saliva was measured by a direct radioimmunoassay RIA The kit is manufactured by LDN GmbH Co KG Nordhorn Germany Cat-No DSL-BA-1200 and is specially made for the quantitative determination of melatonin in saliva The cross-reactivity of the assay for N-acetylserotonin 5-methoxytryptophol and 5-methoxytryptamine is 080 070 and 008 Serotonin 5-methoxyindole-3-acetic acid is 001 respectively The sensitivity of the assay is 1 ngL The intra- and inter-variations are 113 and 12 respectively Salivary cortisol concentrations were measured with a competitive solid-stage radioimmunoassay Coat-A-Count Diagnostic Products Corp DPC The protocol followed the instructions of Coat-Count Free Cortisol in Saliva kit from DPC
Ghrelin assay Plasma immunoreactive ghrelin levels will be measured in duplicate using a commercial radioimmunoassay RIA that uses 125I-labeled bioactive ghrelin as a tracer and a rabbit polyclonal antibody raised against full-length octanoylated human ghrelin Phoenix Pharmaceuticals Belmont CA
Setting
The experiments will take place at the Institute for Sleep and Fatigue medicine the Chaim Sheba Medical Center Tel Hashomer
Subjects
A total of 20 subjects 10 diagnosed as DSPS patients and 10 matched healthy controls with a proven normal sleep-wake cycle
Exclusion criteria for the recruitment would be body mass index BMI higher than 28 or lower than 22 shift-work or chronic disease and chronic medication use
Procedure
Experiment 1- A comparison between 10 normal rhythm and 10 DSPS subjects under restricted sleep-wake schedule
Stage 1 10 day actigraphic monitoring under restricted sleep schedule using alarm clocks DSPS patients will be awakened at 700 am and control subjects will be awakened at 300 am
Stage 2 A 36 hour monitoring of the following measures body temperature melatonin cortisol Ghrelin subjective hunger sensation and eating behavior The subjects will be provided with ad-libitum food and will be instructed to eat whatever they like whenever they feel hungry
Experiment 2- A comparison between 10 normal rhythm and 10 DSPS subjects under ad-libitum sleep conditions
Stage 1 A 10 day actigraphic monitoring under ad-libitum sleep schedule Patients will be instructed to go to sleep whenever they feel tired and avoid any means of unnatural awakening
Stage 2 similar to experiment 1
Experiment 3- Examination of DSPS patients under melatonin administration and ad libitum sleep after 12 weeks of treatment
Stage 1 A 10 day actigraphic monitoring under ad-libitum sleep schedule Patients will be instructed to go to sleep whenever they feel tired and avoid any means of unnatural awakening Melatonin will be taken according to the medical instruction usually at 2200
Stage 2 similar to experiment 1
Measurements
Subjective hunger sensation will be measured with Visual Analogue Scale ratings for appetite assessment Flint et al 2000 Oh et al 2002 Parker et al 2004
Timing of meals and eating behavior will be recorded by the experimenter during the 36-hr monitoring
Sleep-wake rhythm normal or DSPS will be determined using the Actiwatch wrist activity monitoring system Actiwatch Cambridge Neurotechnology LTD
Plasma levels of Ghrelin will be sampled every 2 hours for 36 hours An intravenous catheter will be placed on the subjects arm 30 minutes prior to the first blood sampling Blood samples will be collected with chilled Vacutainer EDTA tubes and immediately centrifuged Plasma Ghrelin will be measured using commercial radioimmunoassay RIA- Phoenix Pharmaceuticals
Salivary levels of Melatonin and Cortisol Saliva will be collected by placing wool swab of plain Salivettes Sarstedt Disposable Products Regency Park Adelaide into the mouths of the subjects with chewing for 5 min Saliva samples will be taken at a total of 18 time points over a 36-h period for each subject The samples will be kept in Salivette tubes in the refrigerator at 4 ºC until the end of each 24-h period The Salivette tubes will be centrifuged for 15 min at 3000 g and the samples frozen at -20 ºC until assayed
Melatonin treatment Subjects with DSPS in the treatment group will be treated with melatonin according to a standard protocol for 3 months before the experiment
Oral temperature will be measured using standard medical mercury thermometer placed under the tongue for 3 minutes at a total of 18 time points over a 36-h period right after the saliva sample collection
Analysis Assays of Melatonin and cortisol Melatonin in saliva was measured by a direct radioimmunoassay RIA The kit is manufactured by LDN GmbH Co KG Nordhorn Germany Cat-No DSL-BA-1200 and is specially made for the quantitative determination of melatonin in saliva The cross-reactivity of the assay for N-acetylserotonin 5-methoxytryptophol and 5-methoxytryptamine is 080 070 and 008 Serotonin 5-methoxyindole-3-acetic acid is 001 respectively The sensitivity of the assay is 1 ngL The intra- and inter-variations are 113 and 12 respectively Salivary cortisol concentrations were measured with a competitive solid-stage radioimmunoassay Coat-A-Count Diagnostic Products Corp DPC The protocol followed the instructions of Coat-Count Free Cortisol in Saliva kit from DPC
Ghrelin assay Plasma immunoreactive ghrelin levels will be measured in duplicate using a commercial radioimmunoassay RIA that uses 125I-labeled bioactive ghrelin as a tracer and a rabbit polyclonal antibody raised against full-length octanoylated human ghrelin Phoenix Pharmaceuticals Belmont CA
Setting
The experiments will take place at the Institute for Sleep and Fatigue medicine the Chaim Sheba Medical Center Tel Hashomer
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None