Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT06201897 |
| Other study ID # |
IECPG156/24.03.2022-OT-12.2023 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
Phase 2/Phase 3
|
| First received |
|
| Last updated |
|
| Start date |
March 2024 |
| Est. completion date |
June 2026 |
Study information
| Verified date |
March 2024 |
| Source |
All India Institute of Medical Sciences, New Delhi |
| Contact |
Sheffali Gulati |
| Phone |
9810386847 |
| Email |
sheffaligulati[@]gmail.com |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
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 30mg/kg/day, pyridoxal phosphate- 20mg/kg/day, biotin 10mg/day and folinic
acid 15mg/day) 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 valproate/levetiracetam 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 U/m2 or 6 U/kg 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 2:1 and then hiked to 2.5:1 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 4:1 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:
140.5 x 41.5 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: Mean/Median/Range/Standard Deviation/Frequencies 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/
Fischer's 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 0.05 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
parents/guardians.
Privacy and confidentiality: Confidentiality of the records will be maintained. The
parents/guardians 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.
