Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05591508 |
| Other study ID # |
IEC-140/06.03.2020 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
November 1, 2022 |
| Est. completion date |
November 30, 2024 |
Study information
| Verified date |
January 2023 |
| Source |
All India Institute of Medical Sciences, New Delhi |
| Contact |
Sheffali Gulati |
| Phone |
01126594679 |
| Email |
sheffaligulati[@]gmail.com |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Ketogenic diet being started early in those with status epilepticus and frequent or abundant
discharges in EEG in comparison to just standard therapy is being evaluated here for efficacy
and adverse effects.
Description:
Study Title : Ketogenic diet for status epilepticus in infants, children and adolescents aged
6 months to 18 years immediately after cessation of convulsive status epilepticus; a
randomized open labelled trial Objective of The study : To evaluate the efficacy of add on
ketogenic diet therapy compared to standard treatment and care of infants, children and
adolescents aged 6 months to 18 years in terms of time taken for reduction in EEG discharges
by >50% (with a baseline of abundant or frequent discharges) after stoppage of convulsive
status epilepticus Justification of the study: Up to one third of epilepsy are medically
intractable, of which only another third is surgically amenable. Ketogenic diet is now an
established modality of treatment in these 20 percent of patients with epilepsy. Various
studies have shown at least up to 50% reduction in seizure frequency with this modality.
The last decade has seen ketogenic diet being used for management of status epilepticus.
Current evidence is only in the form of case series and isolated case reports. Status
epilepticus is associated with significant mortality and morbidity. Aggressive management is
imperative. However, non-convulsive electrographic status may persist beyond cessation of
clinical status in up to 20-30% of cases. Thus in such scenarios, it is controversial whether
to continue aggressive management with anesthetics and numerous antiepileptics, as the effect
may be detrimental. Thus, the current study has been planned to evaluate efficacy of
ketogenic diet in status epilepticus.
Study design: Open labeled randomized controlled trial Study population: Infants, children
and adolescents aged 6 months to 18 years with electrographic evidence of seizure activity
with abundant or frequent discharges immediately after stoppage of convulsive status
epilepticus, attending pediatric inpatient services at AIIMS, New Delhi Assuming time to
cessation of reduction of EEG discharges by > 50% to be 10+5 days in the KD arm and 15+5 in
the non KD arm, with an alpha of 5% and power of 90%, the sample size comes out to be 22 in
each arm. It is being proposed that 25 cases will be recruited in each of the arms.
Inclusion criteria
1. Infants, children and adolescents aged 6 months to 18 years
2. Electrographic evidence of seizure(frequent or abundant discharges in EEG)
3. Clinical status controlled immediately on standard therapy and care based on established
consensus guidelines followed globally Exclusion criteria
1. Circulatory failure
2. GI Intolerance
3. Associated chronic systemic illness
4. Any abnormality on baseline laboratory investigation
5. Neurometabolic disorders (except those in which ketogenic diet is therapy of choice)Up
to one third of epilepsy are medically intractable, of which only another third is
surgically amenable. Ketogenic diet is now an established modality of treatment in these
20 percent of patients with epilepsy. Various studies have shown at least up to 50%
reduction in seizure frequency with this modality.
The last decade has seen ketogenic diet being used for management of status epilepticus.
Current evidence is only in the form of case series and isolated case reports. Status
epilepticus is associated with significant mortality and morbidity. Aggressive management is
imperative. However, non-convulsive electrographic status may persist beyond cessation of
clinical status in up to 20-30% of cases. Thus in such scenarios, it is controversial whether
to continue aggressive management with anesthetics and numerous antiepileptics, as the effect
may be detrimental. Thus, the current study has been planned to evaluate efficacy of
ketogenic diet in non-convulsive electrographic status.
Study design: Open labeled randomized controlled trial Study population: Infants, children
and adolescents aged 6 months to 18 years with electrographic status epilepticus immediately
after stoppage of convulsive status epilepticus, attending Pediatric Intpatient services at
All India Institute of Medical Sciences (AIIMS), New Delhi Sample size calculation Assuming
time to cessation of electrographic status to be 10+-5 days in the KD arm and 15+-5 in the
non KD arm, with an α of 5% and power of 90%, the sample size comes out to be 22 in each arm.
It is being proposed that 25 cases will be recruited in each of the arms.
Inclusion criteria
1. Infants, children and adolescents aged 6 months to 18 years
2. Electrographic status
3. Clinical status controlled immediately on standard therapy and care based on established
consensus guidelines followed globally Exclusion criteria
1. Circulatory failure 2. GI Intolerance 3. Associated chronic systemic illness 4. Any
abnormality on baseline laboratory investigation 5. Neurometabolic disorders (except those in
which ketogenic diet is therapy of choice) Baseline Assessment The components of baseline
assessment of patients are
1. EEG within 6 hours of cessation of clinical status
2. The components of laboratory evaluation will be
• Complete blood count with peripheral smear with RBC indices
• Renal and Liver function tests
• Serum sodium, potassium
• Fasting blood sugar
• Serum total protein and albumin
• Serum calcium, phosphate, alkaline phosphatase
• Serum lipid profile
• Venous blood gas
• Serum uric acid
• Urine Calcium/creatinine ratio
• Arterial lactate
• Serum ammonia
• Urine GCMS
• Blood TMS The last 4 investigations will be done if underlying neurometabolic
condition is suspected.
Randomisation technique Computer generated block randomization will be done to allocate two
groups A and B. Group A will be Add on ketogenic diet therapy + standard care and group B
will be only Standard Care.Allocation concealment will be done using sealed envelopes
Intervention
1. Setting: In patient services in the Department of Pediatrics, AIIMS, New Delhi
2. Duration: If no improvement is seen within 2 weeks of initiation of ketogenic diet, the
therapy will be discontinued. However, in case of response, it will be continued for
atleast 4 weeks and then it will be left to the family whether to continue ketogenic
diet further or not.
3. Type of intervention: Standard of care therapy will be delivered in both the arms. Add
on ketogenic diet therapy will be given to one arm.
Standard of Care Therapy The standard of care therapy for status epilepticus will be
given to patients according to the established global consensus guidelines.
Dietary therapy will be given for atleast 4 weeks in responders. After baseline
investigations, if no contraindication exists, ketogenic diet will be started at the
earliest. Ketogenic diet will be in the form of artificial powder which can be diluted
and given through NG tube. It will be started at a ratio of 1:1 followed by daily
increment (2:1,3:1 and 4:1) till a urine ketone of 2+ is seen.
The laboratory parameters will be repeated weekly twice on dietary therapy. In case of
any abnormality in these investigations, standard established protocol will be followed
for management.[84] The tests may be performed more frequently if the clinical condition
of the patient demanded so.
All the patients will be started on oral calcium, levocarnitine (50mg/kg/day, maximum1
gm)and multivitamin tablets.
Families which opt to continue dietary therapy beyond 4 weeks, standard established
protocol will be followed.
Statistical analysis Baseline variables will be appropriately recorded as continuous or
discrete. Comparison between the 2 groups will be done using appropriate bivariate
analysis.
Timelines
• Enrolment of patients: 0 to 24months
• Intervention and follow up: 0 to 25 months
• Data analysis: 25 to 30 months
.
1. Data management and statistical 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
Categorical variables would be compared using chi square/ Fischer's 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 will not only provide unifying insights into multiple aspects of autism, with
attendant benefits for improving diagnosis and therapy but also help in bringing this special
kind of children/adults to mainstream society.
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 tests- It will be borne by ICMR, DST, DBT Welcome trust
6.5. Study design: Open labelled randomized controlled trial
6.6 Dosages of drug: Ketogenic diet will be in the form of artificial powder which can be
diluted and given through NG tube. It will be started at a ratio of 1:1 followed by daily
increment (2:1,3:1 and 4:1) till a urine ketone of 2+ is seen.
6.7 Duration of treatment: Dietary therapy will be given for at least 4 weeks in responders.
After baseline investigations
6.8 Investigation: The components of baseline investigations of patients are
1. EEG within 6 hours of cessation of clinical status
2. The components of laboratory evaluation will be • Complete blood count with peripheral
smear with RBC indices • Renal and Liver function tests • Serum sodium, potassium •
Fasting blood sugar • Serum total protein and albumin • Serum calcium, phosphate,
alkaline phosphatase • Serum lipid profile
• Venous blood gas
• Serum uric acid
• Urine Calcium/creatinine ratio
• Arterial lactate
- Serum ammonia
- Urine GCMS
- Blood TMS The last 4 investigations will be done if underlying neurometabolic
condition is suspected.
