Ignite Creation Date:
2024-05-06 @ 7:59 PM
Last Modification Date:
2024-10-26 @ 3:17 PM
Study NCT ID:
NCT06201897
Status:
RECRUITING
Last Update Posted:
2024-03-04
First Post:
2024-01-01
Brief Title:
Cortical Excitability in West Syndrome Using Transcranial Magnetic Stimulation
Sponsor:
All India Institute of Medical Sciences New Delhi
Organization:
All India Institute of Medical Sciences New Delhi
Study Overview
Official Title:
Comparison of Pre- and Post- Therapy Real Time Cortical Excitability in West Syndrome Using Transcranial Magnetic Stimulation A Longitudinal Cohort Study
Status:
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:
Currently no literature is available regarding degree of cortical excitability and its correlation with various epileptic syndromes and disorders such as West Syndrome in pediatric age group Studying the complex interaction of cortical excitability seizures neurobehavioral patterns and brain maturation in children may provide valuable information and new insights about the underlying neuropathogenic pathways in childhood epilepsy West Syndrome is a unique epilepsy syndrome amalgamating infantile onset epilepsy with significant neurodevelopmental delay Due to this reason it is the ideal disorder to study this complex interaction How cortical excitability correlates with disease activity in West Syndrome is speculative The ability of disease characteristics such as degree of cortical excitability to predict successful outcome after ACTH therapy non-invasive biomarker of treatment response in children with West Syndrome has not been explored
Most importantly the present study may be a hypothesis generating initial step bringing new insights into neurocognitive effects of seizures seizure pathogenesis individualized antiepileptic drug therapy and for studying treatment response
The investigators aim to determine the change in cortical excitability pre and post ACTH therapy in children with West syndrome and whether the change predicts responsiveness to ACTH therapy in terms of reduction in spasm frequency at 12 weeks
Most importantly the present study may be a hypothesis generating initial step bringing new insights into neurocognitive effects of seizures seizure pathogenesis individualized antiepileptic drug therapy and for studying treatment response
The investigators aim to determine the change in cortical excitability pre and post ACTH therapy in children with West syndrome and whether the change predicts responsiveness to ACTH therapy in terms of reduction in spasm frequency at 12 weeks
Detailed Description:
PATIENT ENROLLMENT AND MANAGEMENT
Consecutive children with West Syndrome clinical spasm with EEG correlate will be screened in the study centre for eligibility and after applying inclusion and exclusion criteria they will be worked up for etiology
History will be taken and clinical examination will be done and if either are suggestive of any underlying etiology specific investigations will be performed as indicated Ex Neurocutaneous markers in tuberous sclerosis
If there are no other etiological pointers available from history and examination or if there is any history suggestive of adverse perinatal events MRI brain with epilepsy protocol will be done
If MRI is not suggestive of structural etiology they will be given a vitamin trial pyridoxine 30mgkgday pyridoxal phosphate- 20mgkgday biotin 10mgday and folinic acid 15mgday for a period of 10 days for response Those who respond to vitamin trial will be excluded from the study
Written informed consent will be taken from legal guardians who are willing to participate in the study Their anti-epileptic drugs will be optimized Inappropriate AEDs like phenytoin phenobarbitone and carbamazepine will be discontinued and replaced with valproatelevetiracetam and clonazepam in adequate doses and will be made in tablet form
DASII will be administered by child psychologist and will be repeated at 6 months of follow-up wherever feasible
ACTH therapy
Appropriate screening for Tuberculosis as per unit protocol Mantoux and CXR screening will be done if going to receive ACTH therapy
Children fulfilling the inclusion and exclusion criteria will be enrolled and started on high dose regimen of 150 Um2 or 6 Ukg of ACTH
This high dose will be continued for 2 weeks following which they will be slowly tapered over remaining 4 weeks for a total treatment duration of 6 weeks
RBS and BP monitoring to be done twice weekly
EEG and TMS parameters will be done at baseline 6 weeks and 3 months of therapy
First follow-up will be at 6 weeks of treatment initiation then at 8 weeks and from then on once a month for a minimum period of 3 months - 7 days upto 6 months - 7 days wherever feasible
Those who have had complete electroclinical spasm cessation will be continued of oral AEDs
The overall spasm reduction will be calculated from the mean number of spasms from the observation period week and the mean number of spasms from the 6th week of therapy Adverse effects will be noted down in their seizure diary
For sustained electroclinical cessation those who had complete electroclinical response will be rechecked at the end of 3 months - 7 days upto 6 months - 7 days wherever feasible
Compliance rate adverse events 50 spasm reduction rate clinical spasm cessation rate complete electroclinical spasm cessation rate will also be calculated from patient seizure log and EEG correlate
After 3 months those who have 50 spasm reduction rate will be given trial of other oral AEDs as per protocol
But those who have 50 spasm reduction rate will be given an option to choose between ketogenic diet and vigabatrin
KD therapy
Children who have 50 spasm reduction rate and opt for ketogenic diet will be explained and counselled regarding the process of initiation and maintenance of dietary therapy
A window period of 5 to 7 days will be given for the pre-initiation of KD workup which includes ECG RFT LFT CBC Lipid profile Urine calcium creatinine ratio and USG KUB for nephrocalcinosis
Children will be admitted in ward and initiated on Ketogenic diet under supervision
KD will be initiated in a ratio of 21 and then hiked to 251 in the next day and subsequently to 3 on day 3 Urine ketones will be checked daily using ketone dipsticks
For better assurance of ketosis and tolerance the indigenous KD will be supplemented with readymade formula for the initial period of 4 weeks after starting KD and then shifted to complete indigenous KD gradually over 1 week
If ketosis is not achieved by day 5 of starting KD the ratio will be hiked to a maximum of 41 from day 6
Patient will be discharged as soon as the desired ratio of KD is achieved and the parents are adequately motivated and confident Telephonic contacts will be made in regular intervals to further ensure compliance at home
Those children who are unable to tolerate taking adequate ketogenic diet therapy requiring discontinuation of therapy will be considered as deviates
The overall spasm reduction will be calculated from the mean number of spasms from the observation period week and the mean number of spasms from the 6th week of KD therapy
Failure of KD Children with response rate if not 50 spasm reduction by 6 weeks or no electroclinical cessation of spasm by 3 months will be considered to have failed KD and shifted to standard anti-seizure medications as per protocol
KD will be continued if there is more than 50 spasm reduction
EEG and TMS will be done at 6 weeks and 3 months of KD therapy in case of clinical spasm cessation and wherever clinically indicated
First follow-up will be at 6 weeks of KD treatment initiation 8 weeks and then once monthly for a minimum period of 3 months and 6 months wherever feasible For sustained electroclinical cessation those who had complete electroclinical response will be rechecked at the end of 3 months - 7 days upto 6 months - 7 days wherever feasible
Compliance rate adverse events 50 spasm reduction rate clinical spasm cessation rate complete electroclinical spasm cessation rate will also be calculated from patient seizure log and EEG correlate
Formula based KD would be supplied to the patient free of cost But the company will play no part in the study design conduct data collection or analysis
TMS Intervention Protocol
PARAMETERS METHODS Resting Motor Threshold MT - Single pulse TMS Site of stimulation - Motor Cortex Coil type- Circular coil MCF-125 Coil outer diameter 121 mm Transducer head 1405 x 415 mm Hemisphere - Bilateral hemisphere EMG recording - Contralateral APB muscle
Short interval cortical inhibition SICI - Paired pulse TMS in dominant hemisphere ISI - 3 msec Conditioning pulse - 80 of MT Test stimulus - 120 of MT
Long interval cortical inhibition SICI - Paired pulse TMS in dominant hemisphere ISI - 100 msec Conditioning pulse - 120 of MT Test stimulus - 120 of MT
Total Time Duration - 30 min The TMS will be given by machine make Magventure model no X100 with Magoption made in Denmark with standard circular coil as mentioned above
Data Management and Analysis Data recording would be done in a Microsoft Excel spreadsheet Microsoft Office Microsoft Corp Seattle WA USA
Descriptive MeanMedianRangeStandard DeviationFrequencies would be used to describe the demographic profile of participants and their comorbidities Comparative A comparison between the two groups would be done Categorical variables would be compared using Chi square Fischers exact test Depending upon the distribution of continuous variables -
Student t test would be used for parametric variables
Mann Whitney U test would be used for nonparametric variables Differences with p value of 005 or lower will be considered significant Ethical aspects Ethical clearance The study will be conducted after obtaining Ethical clearance from the Institute Ethical Committee
Essentiality and Justification for the study This study would be beneficial in generating a hypothesis as an initial step bringing new insights into seizure pathogenesis planning individualized antiepileptic drug therapy and studying treatment response
Consent Patients will be enrolled only after obtaining informed written consent from the parentsguardians
Privacy and confidentiality Confidentiality of the records will be maintained The parentsguardians will have full authority to enroll or withdraw the child from the study and this will not affect the future care and treatment given to the child in our hospital
Costs of the investigations and therapy Investigations such as EEG and TMS whenever required will be done at no additional cost
Immunotherapy which is the standard of care will be provided to the patient All children included in the study would be examined in detail and the investigations and standard of care would be advised after they have fulfilled the inclusion criteria Since the investigators would be following the standard of care in every child hence every child enrolled would be benefitted
The side effects and details of the investigations and intervention shall be explained to the parents in the language they understand the best and consent will be taken accordingly
Consecutive children with West Syndrome clinical spasm with EEG correlate will be screened in the study centre for eligibility and after applying inclusion and exclusion criteria they will be worked up for etiology
History will be taken and clinical examination will be done and if either are suggestive of any underlying etiology specific investigations will be performed as indicated Ex Neurocutaneous markers in tuberous sclerosis
If there are no other etiological pointers available from history and examination or if there is any history suggestive of adverse perinatal events MRI brain with epilepsy protocol will be done
If MRI is not suggestive of structural etiology they will be given a vitamin trial pyridoxine 30mgkgday pyridoxal phosphate- 20mgkgday biotin 10mgday and folinic acid 15mgday for a period of 10 days for response Those who respond to vitamin trial will be excluded from the study
Written informed consent will be taken from legal guardians who are willing to participate in the study Their anti-epileptic drugs will be optimized Inappropriate AEDs like phenytoin phenobarbitone and carbamazepine will be discontinued and replaced with valproatelevetiracetam and clonazepam in adequate doses and will be made in tablet form
DASII will be administered by child psychologist and will be repeated at 6 months of follow-up wherever feasible
ACTH therapy
Appropriate screening for Tuberculosis as per unit protocol Mantoux and CXR screening will be done if going to receive ACTH therapy
Children fulfilling the inclusion and exclusion criteria will be enrolled and started on high dose regimen of 150 Um2 or 6 Ukg of ACTH
This high dose will be continued for 2 weeks following which they will be slowly tapered over remaining 4 weeks for a total treatment duration of 6 weeks
RBS and BP monitoring to be done twice weekly
EEG and TMS parameters will be done at baseline 6 weeks and 3 months of therapy
First follow-up will be at 6 weeks of treatment initiation then at 8 weeks and from then on once a month for a minimum period of 3 months - 7 days upto 6 months - 7 days wherever feasible
Those who have had complete electroclinical spasm cessation will be continued of oral AEDs
The overall spasm reduction will be calculated from the mean number of spasms from the observation period week and the mean number of spasms from the 6th week of therapy Adverse effects will be noted down in their seizure diary
For sustained electroclinical cessation those who had complete electroclinical response will be rechecked at the end of 3 months - 7 days upto 6 months - 7 days wherever feasible
Compliance rate adverse events 50 spasm reduction rate clinical spasm cessation rate complete electroclinical spasm cessation rate will also be calculated from patient seizure log and EEG correlate
After 3 months those who have 50 spasm reduction rate will be given trial of other oral AEDs as per protocol
But those who have 50 spasm reduction rate will be given an option to choose between ketogenic diet and vigabatrin
KD therapy
Children who have 50 spasm reduction rate and opt for ketogenic diet will be explained and counselled regarding the process of initiation and maintenance of dietary therapy
A window period of 5 to 7 days will be given for the pre-initiation of KD workup which includes ECG RFT LFT CBC Lipid profile Urine calcium creatinine ratio and USG KUB for nephrocalcinosis
Children will be admitted in ward and initiated on Ketogenic diet under supervision
KD will be initiated in a ratio of 21 and then hiked to 251 in the next day and subsequently to 3 on day 3 Urine ketones will be checked daily using ketone dipsticks
For better assurance of ketosis and tolerance the indigenous KD will be supplemented with readymade formula for the initial period of 4 weeks after starting KD and then shifted to complete indigenous KD gradually over 1 week
If ketosis is not achieved by day 5 of starting KD the ratio will be hiked to a maximum of 41 from day 6
Patient will be discharged as soon as the desired ratio of KD is achieved and the parents are adequately motivated and confident Telephonic contacts will be made in regular intervals to further ensure compliance at home
Those children who are unable to tolerate taking adequate ketogenic diet therapy requiring discontinuation of therapy will be considered as deviates
The overall spasm reduction will be calculated from the mean number of spasms from the observation period week and the mean number of spasms from the 6th week of KD therapy
Failure of KD Children with response rate if not 50 spasm reduction by 6 weeks or no electroclinical cessation of spasm by 3 months will be considered to have failed KD and shifted to standard anti-seizure medications as per protocol
KD will be continued if there is more than 50 spasm reduction
EEG and TMS will be done at 6 weeks and 3 months of KD therapy in case of clinical spasm cessation and wherever clinically indicated
First follow-up will be at 6 weeks of KD treatment initiation 8 weeks and then once monthly for a minimum period of 3 months and 6 months wherever feasible For sustained electroclinical cessation those who had complete electroclinical response will be rechecked at the end of 3 months - 7 days upto 6 months - 7 days wherever feasible
Compliance rate adverse events 50 spasm reduction rate clinical spasm cessation rate complete electroclinical spasm cessation rate will also be calculated from patient seizure log and EEG correlate
Formula based KD would be supplied to the patient free of cost But the company will play no part in the study design conduct data collection or analysis
TMS Intervention Protocol
PARAMETERS METHODS Resting Motor Threshold MT - Single pulse TMS Site of stimulation - Motor Cortex Coil type- Circular coil MCF-125 Coil outer diameter 121 mm Transducer head 1405 x 415 mm Hemisphere - Bilateral hemisphere EMG recording - Contralateral APB muscle
Short interval cortical inhibition SICI - Paired pulse TMS in dominant hemisphere ISI - 3 msec Conditioning pulse - 80 of MT Test stimulus - 120 of MT
Long interval cortical inhibition SICI - Paired pulse TMS in dominant hemisphere ISI - 100 msec Conditioning pulse - 120 of MT Test stimulus - 120 of MT
Total Time Duration - 30 min The TMS will be given by machine make Magventure model no X100 with Magoption made in Denmark with standard circular coil as mentioned above
Data Management and Analysis Data recording would be done in a Microsoft Excel spreadsheet Microsoft Office Microsoft Corp Seattle WA USA
Descriptive MeanMedianRangeStandard DeviationFrequencies would be used to describe the demographic profile of participants and their comorbidities Comparative A comparison between the two groups would be done Categorical variables would be compared using Chi square Fischers exact test Depending upon the distribution of continuous variables -
Student t test would be used for parametric variables
Mann Whitney U test would be used for nonparametric variables Differences with p value of 005 or lower will be considered significant Ethical aspects Ethical clearance The study will be conducted after obtaining Ethical clearance from the Institute Ethical Committee
Essentiality and Justification for the study This study would be beneficial in generating a hypothesis as an initial step bringing new insights into seizure pathogenesis planning individualized antiepileptic drug therapy and studying treatment response
Consent Patients will be enrolled only after obtaining informed written consent from the parentsguardians
Privacy and confidentiality Confidentiality of the records will be maintained The parentsguardians will have full authority to enroll or withdraw the child from the study and this will not affect the future care and treatment given to the child in our hospital
Costs of the investigations and therapy Investigations such as EEG and TMS whenever required will be done at no additional cost
Immunotherapy which is the standard of care will be provided to the patient All children included in the study would be examined in detail and the investigations and standard of care would be advised after they have fulfilled the inclusion criteria Since the investigators would be following the standard of care in every child hence every child enrolled would be benefitted
The side effects and details of the investigations and intervention shall be explained to the parents in the language they understand the best and consent will be taken accordingly
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