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

NCT05279118 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: IECPG-19/27.1.2022,RT/24.2.22No.3/2/June2022/PG-Thesis
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 2

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.

Conditions

Ketogenic Diet; West Syndrome; Infantile Spasm; ACTH

Keywords

Ketogenic diet; West Syndrome; Infantile Spasm; ACTH

Outcome Measures

Primary Outcomes (1)

• 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

  From baseline to 6 weeks of therapy

Secondary Outcomes (7)

• 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)

Study Arms (2)

Ketogenic diet arm

EXPERIMENTAL

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

Dietary Supplement: Ketogenic diet

ACTH arm

ACTIVE COMPARATOR

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.

Drug: ACTH

Interventions

Ketogenic diet DIETARY_SUPPLEMENT

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

Also known as: Diet therapy

Ketogenic diet arm

ACTH DRUG

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.

Also known as: Hormonal therapy

ACTH arm

Eligibility Criteria

• Age: 6 Months - 2 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

• 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)

Sponsors & Collaborators

• All India Institute of Medical Sciences: lead

Study Sites (2)

All India Institute of Medical Sciences

New Delhi, National Capital Territory of Delhi, 110029, India

Location

AIIMS

New Delhi, 110049, India

Location

MeSH Terms

Conditions

Spasms, Infantile

Interventions

Diet, Ketogenic; Diet Therapy; Adrenocorticotropic Hormone

Condition Hierarchy (Ancestors)

Epilepsy, Generalized; Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epileptic Syndromes

Intervention Hierarchy (Ancestors)

Diet, Carbohydrate-Restricted; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Melanocortins; Pro-Opiomelanocortin; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pituitary Hormones, Anterior; Pituitary Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Nerve Tissue Proteins; Proteins

Study Officials

• Sheffali Gulati

  All India Institute of Medical Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: pilot randomized RCT

Study Record Dates

• First Submitted: March 3, 2022
• First Posted: March 15, 2022
• Study Start: April 18, 2022
• Primary Completion: July 1, 2024
• Study Completion: July 28, 2024
• Last Updated: June 25, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

IN (2)