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Ketogenic Diet vs ACTH for the Treatment of Children With West Syndrome

Primary Purpose

Ketogenic Diet, West Syndrome, Infantile Spasm

Status
Recruiting
Phase
Phase 2
Locations
India
Study Type
Interventional
Intervention
Ketogenic diet
ACTH
Sponsored by
All India Institute of Medical Sciences, New Delhi
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ketogenic Diet focused on measuring Ketogenic diet, West Syndrome, Infantile Spasm, ACTH

Eligibility Criteria

6 Months - 2 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Children, aged 6 month - 2 years with electroclinical diagnosis of west syndrome

Exclusion Criteria:

  • Already on ACTH, prednisolone vigabatrin or KD therapy > 5days
  • Tuberous sclerosis
  • Vitamin trial responsiveness
  • Known Pre-existing contraindications for KD (IEM, Porphyria etc.)
  • Chronic systemic illness (Ex: Chronic kidney disease, congenital heart diseases etc)

Sites / Locations

  • All India Institute of Medical SciencesRecruiting
  • AIIMSRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Ketogenic diet arm

ACTH arm

Arm Description

Children who have consented to the study and have been randomised to ketogenic diet arm will get ketogenic diet under supervision while starting with rapid hiking of lipid to carbohydrate ratio and primary response will be assessed at 6 weeks. Ketogenic diet ratio will be hiked quickly upto a maximum of 4:!. The duration of ketogenic diet can be extended beyond the period of study based on response and parental choice. A minimum period of 6 weeks of diet therapy will be undertaken baring any undue adverse effects when the primary outcome will be assessed

ACTH is the current standard therapy for children with west syndrome. Those who have been randomised to this arm will be started on high dose ACTH for 2 weeks followed by gradual tapering over remaining 4 weeks and primary response documented at 6 weeks of therapy. The high dose ACTh is 150U/m2 or 6U/kg dose administered IM daily for two weeks. After this the doses will be tapered gradually and ACTH will be stopped by 4 weeks for a total treatment duration of strictly 6 weeks.

Outcomes

Primary Outcome Measures

Mean percentage reduction of spam (Baseline mean weekly spasm rate - mean weekly spasm rate on 6th week of therapy/Baseline mean weekly spasm rate * 100) is compared in both arms
Mean percentage reduction of spam (Baseline mean weekly spasm rate - mean weekly spasm rate on 6th week of therapy/Baseline mean weekly spasm rate * 100) is compared in both arms

Secondary Outcome Measures

To compare complete spasm cessation rate in KD arm vs ACTH arm
Percentage of children with clinical spasm cessation at 6 weeks of therapy
To compare >50% spasm reduction rate in KD arm vs ACTH arm
Percentage of children with >50% spasm reduction at the end of 6 weeks and 3months of therapy (wherever feasible at 6 months)
To compare electroclinical spasm To compare electroclinical spasm cessation rate in KD arm vs ACTH arm at 6 weeks
Percentage of children with clinical spasm cessation at 6 weeks of therapy
To compare sustained electroclinical cessation rate in KD arm vs ACTH arm at 3 months
Percentage of children with primary electroclinical spasm cessation who sustain the remission at 3months of therapy(wherever feasible at 6 months)
To compare the compliance rate in KD arm vs ACTH arm at 6 weeks
Percentage of children with compliance of greater than >80% of doses of ACTH in the 6 weeks of therapy compared with percentage of children with score of >80% in KD compliance questionnaire (score of >/=18 out of 25)
To compare the adverse effect profile in KD arm vs ACTH arm at 6 weeks and 3 months
Description of adverse effects in each groups with proportion of CTCAE grade 3 and above in each groups at 3months of therapy (wherever feasible at 6 months)
To compare neurodevelopmental outcome in KD arm vs ACTH arm using DASII at 3 months
Percentage improvement in Motor and Mental developmental quotients of children in both groups at 3 months of therapy (wherever feasible at 6 months)

Full Information

First Posted
March 3, 2022
Last Updated
January 27, 2023
Sponsor
All India Institute of Medical Sciences, New Delhi
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1. Study Identification

Unique Protocol Identification Number
NCT05279118
Brief Title
Ketogenic Diet vs ACTH for the Treatment of Children With West Syndrome
Official Title
Comparison of Efficacy of Ketogenic Diet and ACTH Therapy Among Children With West Syndrome: A Pilot Randomized Control Trial
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 1, 2022 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
All India Institute of Medical Sciences, New Delhi

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Children with West syndrome are prone to refractory seizures with poor neurocognitive outcome overall. The current standard of care consists of treatment with ACTH, but the grade of evidence is not high and not much RCTs are available. Ketogenic diet is an effective and well tolerated treatment option in drug refractory epilepsy and also in refractory west syndrome. In view of minimal side effects, better cost parameters and ability to continue for a longer duration our study aiims to investigate the efficacy of ketogenic diet as a first line therapy in comparison to ACTH therapy. Children with west syndrome after satisfying the inclusion and exclusion criteria will be randomised into the two treatment arms and primary response will be noted at the end of 6 weeks of therapy in terms of mean percentage of spasm reduction.
Detailed Description
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 optimised. 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. There will be an observation period of 2 weeks where the participants will be sensitised about proper counting of spasms and the mean no. of spasms per week of the 2nd week will form the baseline and they will be randomised into two groups as mentioned above during the same period with no further changes in AEDs till the duration of completion of primary objective. Those who require hiking/titrating of AEDs during the initial period of 6 weeks plus run in period of 2 weeks will be treated as deviates and excluded from the study. DASII will be administered by child psychologist and will be repeated at 3 months and at 6 months of followup wherever feasible. Appropriate screening for Tuberculosis as per unit protocol (Mantoux and CXR screening) will be done if going to the ACTH therapy arm. Workup for ketogenic diet will also be done ECG, RFT, LFT, CBC, Lipid profile, Urine calcium creatinine ratio and USG KUB for nephrocalcinosis if going to the KD arm Group 1 ACTH arm: Children randomised into ACTH arm will be started on high dose regimen(45)(46) of 150U/m2 or 6U/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. EEG will be done at 6 weeks and 3 months of therapy in case of clinical spasm cessation and wherever clinically indicated First followup 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. Those who have <50% spasm reduction rate will be shifted to KD. Those who have >/=50% spasm reduction rate will be given trial of other oral AEDs as per protocol. 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. RBS and BP monitoring to be done twice weekly Group 2 KD arm: Children randomised into this arm 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 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 4th week of 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 ACTH therapy as per protocol. KD will be continued if there is more than 50% spasm reduction. EEG will be done at 6 weeks and 3 months of therapy in case of clinical spasm cessation and wherever clinically indicated First followup will be at 6 weeks of treatment initiation,8weeks 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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ketogenic Diet, West Syndrome, Infantile Spasm, ACTH
Keywords
Ketogenic diet, West Syndrome, Infantile Spasm, ACTH

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Model Description
pilot randomized RCT
Masking
None (Open Label)
Allocation
Randomized
Enrollment
80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Ketogenic diet arm
Arm Type
Experimental
Arm Description
Children who have consented to the study and have been randomised to ketogenic diet arm will get ketogenic diet under supervision while starting with rapid hiking of lipid to carbohydrate ratio and primary response will be assessed at 6 weeks. Ketogenic diet ratio will be hiked quickly upto a maximum of 4:!. The duration of ketogenic diet can be extended beyond the period of study based on response and parental choice. A minimum period of 6 weeks of diet therapy will be undertaken baring any undue adverse effects when the primary outcome will be assessed
Arm Title
ACTH arm
Arm Type
Active Comparator
Arm Description
ACTH is the current standard therapy for children with west syndrome. Those who have been randomised to this arm will be started on high dose ACTH for 2 weeks followed by gradual tapering over remaining 4 weeks and primary response documented at 6 weeks of therapy. The high dose ACTh is 150U/m2 or 6U/kg dose administered IM daily for two weeks. After this the doses will be tapered gradually and ACTH will be stopped by 4 weeks for a total treatment duration of strictly 6 weeks.
Intervention Type
Dietary Supplement
Intervention Name(s)
Ketogenic diet
Other Intervention Name(s)
Diet therapy
Intervention Description
Children who have consented to the study and have been randomised to ketogenic diet arm will get ketogenic diet under supervision while starting with rapid hiking of lipid to carbohydrate ratio and primary response will be assessed at 6 weeks. Ketogenic diet ratio will be hiked quickly upto a maximum of 4:!. The duration of ketogenic diet can be extended beyond the period of study based on response and parental choice. A minimum period of 6 weeks of diet therapy will be undertaken baring any undue adverse effects when the primary outcome will be assessed
Intervention Type
Drug
Intervention Name(s)
ACTH
Other Intervention Name(s)
Hormonal therapy
Intervention Description
ACTH is the current standard therapy for children with west syndrome. Those who have been randomised to this arm will be started on high dose ACTH for 2 weeks followed by gradual tapering over remaining 4 weeks and primary response documented at 6 weeks of therapy. The high dose ACTh is 150U/m2 or 6U/kg dose administered IM daily for two weeks. After this the doses will be tapered gradually and ACTH will be stopped by 4 weeks for a total treatment duration of strictly 6 weeks.
Primary Outcome Measure Information:
Title
Mean percentage reduction of spam (Baseline mean weekly spasm rate - mean weekly spasm rate on 6th week of therapy/Baseline mean weekly spasm rate * 100) is compared in both arms
Description
Mean percentage reduction of spam (Baseline mean weekly spasm rate - mean weekly spasm rate on 6th week of therapy/Baseline mean weekly spasm rate * 100) is compared in both arms
Time Frame
From baseline to 6 weeks of therapy
Secondary Outcome Measure Information:
Title
To compare complete spasm cessation rate in KD arm vs ACTH arm
Description
Percentage of children with clinical spasm cessation at 6 weeks of therapy
Time Frame
Percentage of children with clinical spasm cessation at 6 weeks of therapy
Title
To compare >50% spasm reduction rate in KD arm vs ACTH arm
Description
Percentage of children with >50% spasm reduction at the end of 6 weeks and 3months of therapy (wherever feasible at 6 months)
Time Frame
Percentage of children with >50% spasm reduction at the end of 6 weeks and 3months of therapy (wherever feasible at 6 months)
Title
To compare electroclinical spasm To compare electroclinical spasm cessation rate in KD arm vs ACTH arm at 6 weeks
Description
Percentage of children with clinical spasm cessation at 6 weeks of therapy
Time Frame
Percentage of children with clinical spasm cessation at 6 weeks of therapy
Title
To compare sustained electroclinical cessation rate in KD arm vs ACTH arm at 3 months
Description
Percentage of children with primary electroclinical spasm cessation who sustain the remission at 3months of therapy(wherever feasible at 6 months)
Time Frame
Percentage of children with primary electroclinical spasm cessation who sustain the remission at 3months of therapy(wherever feasible at 6 months)
Title
To compare the compliance rate in KD arm vs ACTH arm at 6 weeks
Description
Percentage of children with compliance of greater than >80% of doses of ACTH in the 6 weeks of therapy compared with percentage of children with score of >80% in KD compliance questionnaire (score of >/=18 out of 25)
Time Frame
Percentage of children with compliance of greater than >80% of doses of ACTH in the 6 weeks of therapy compared with percentage of children with score of >80% in KD compliance questionnaire (score of >/=18 out of 25)
Title
To compare the adverse effect profile in KD arm vs ACTH arm at 6 weeks and 3 months
Description
Description of adverse effects in each groups with proportion of CTCAE grade 3 and above in each groups at 3months of therapy (wherever feasible at 6 months)
Time Frame
Description of adverse effects in each groups with proportion of CTCAE grade 3 and above in each groups at 3months of therapy (wherever feasible at 6 months)
Title
To compare neurodevelopmental outcome in KD arm vs ACTH arm using DASII at 3 months
Description
Percentage improvement in Motor and Mental developmental quotients of children in both groups at 3 months of therapy (wherever feasible at 6 months)
Time Frame
Percentage improvement in Motor and Mental developmental quotients of children in both groups at 3 months of therapy (wherever feasible at 6 months)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Months
Maximum Age & Unit of Time
2 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Children, aged 6 month - 2 years with electroclinical diagnosis of west syndrome Exclusion Criteria: Already on ACTH, prednisolone vigabatrin or KD therapy > 5days Tuberous sclerosis Vitamin trial responsiveness Known Pre-existing contraindications for KD (IEM, Porphyria etc.) Chronic systemic illness (Ex: Chronic kidney disease, congenital heart diseases etc)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sheffali Gulati
Phone
01126594679
Email
sheffaligulati@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Sheffali Gulati
Phone
9810386847
Email
sheffaligulati1@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sheffali Gulati
Organizational Affiliation
All India Institute of Medical Sciences, New Delhi
Official's Role
Principal Investigator
Facility Information:
Facility Name
All India Institute of Medical Sciences
City
New Delhi
State/Province
Delhi
ZIP/Postal Code
110029
Country
India
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gulati Sheffali, MD
Phone
9868397532
Email
sheffaligulati@gmail.com
First Name & Middle Initial & Last Name & Degree
Gulati Sheffali, MD
Facility Name
AIIMS
City
New Delhi
ZIP/Postal Code
110049
Country
India
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
SHEFFALI GULATI

12. IPD Sharing Statement

Plan to Share IPD
No

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Ketogenic Diet vs ACTH for the Treatment of Children With West Syndrome

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