Efficacy of Low Glycemic Index Diet vs Modified Atkins Diet and Gluten Free Casein Free Diet as add-on Therapy With Standard of Care in Children With Autism Spectrum Disorder

Condition(s) studied

Investigational drug(s) / intervention(s)

Low glycemic index diet with standard of care: Low glycemic index diet would involve the exclusion of foods with medium and high glycemic index (above 50) from the diet. Total carbohydrate intake permitted will be upto 40-60 g/day (or 10% of calorie intake, whichever is lesser). Pre diet workup including CBC, RFT, LFT, fasting lipid profile, ECG, urine calcium : creatinine ratio and 12 lead ECG would be performed prior and diet initiated if normal. Baseline nutritional assessment and anthropometry would be performed. The diet would be introduced gradually over 2 weeks and given for 6 months. Standard of care including speech therapy, behavioural and occupational therapy will be continued throughout the intervention period.

Modified Atkins diet with standard of care: Modifed Atkins diet is a less restrictive version of ketogenic diet, which is a high fat, low carbohydrate diet in which carbohydrate content is limited to 10g at initiation. The ketogenic ratio approximates to 1:1 at initiation, with no mandate on a set ratio. There will be no restriction on calories, protein or fluid intake. Baseline nutritional assessment and anthropometry would be performed. Pre diet workup including CBC, RFT, LFT, fasting lipid profile, ECG, urine calcium : creatinine ratio and 12 lead ECG would be performed prior and diet initiated if normal. The diet would be introduced gradually over 2 weeks and given for 6 months. Urine ketones will be measured daily using dipstick. Standard of care including speech therapy, behavioural and occupational therapy will be continued throughout the intervention period.

Gluten free casein free diet with standard of care: Gluten free casein free diet involves exclusion of gluten (wheat, rye, oats and barley) and casein (milk and milk products) containing foods. Baseline nutritional assessment and anthropometry will be performed. Pre diet workup in the form of CBC, RFT, LFT, urine calcium:creatinine ratio, fasting lipid profile, 12 lead ECG and USG KUB will be performed and diet initiated if normal. The diet will be introduced gradually over 2 weeks and continued for 6 months. Standard of care including speech therapy, behavioural and occupational therapy will be continued throughout the intervention period.

Study summary

Autism spectrum disorder (ASD) is a heterogenous, lifelong neurodevelopmental disorder with deficits in social communication and restrictive, repetitive patterns of behavior, with onset in the early developmental period leading to significant impairment in adaptive functioning. With the rising prevalence of ASD and expanding access to early intervention programs, there is a need for more efficacious therapies with a biological basis as additional interventions along with standard of care. The rationale for dietary therapies in autism being, the high rate of GI comorbidities and dysbiosis. Based on evidence from our centre, add-on modified Atkins diet and add-on gluten free, casein-free diet are superior to standard of care alone in improving core deficits (measured by CARS-2 score at 6 months ) in children with ASD. Low glycemic index diet is a comparitively less restricitive diet with better adverse effect profile, with preclinical evidence in ASD. It has been proven to be non inferior to MAD for drug refractory epilepsy, with no clinical trials in ASD. This clinical trial aims to learn if add-on low glycemic index diet works as well as modified Atkins diet and gluten free casein free diet along with standard of care in children aged 3 to 8 years with Autism Spectrum Disorder. The main question it aims to answer is:

In children aged 3 to 8 years with Autism Spectrum Disorder, what is the comparative efficacy of add-on low glycemic index diet versus Modified Atkins diet and Gluten free Casein free diet along with standard of care in reducing the CARS-2 score at 6 months post intervention?

Eligible children aged 3-8 years with ASD will be randomised into three arms:

1. Low Glycemic Index diet arm: foods with glycemic index \>50 would be excluded
2. Modified Atkins diet arm: a high-fat, low carbohydrate diet in which carbohydrate intake would be restricted to 10 g/day
3. Gluten-free casein-free diet arm: gluten (oats, barley, wheat, rye) and casein (milk and milk products) containing foods would be excluded

In all three arms, in addition to diet, standard of care involving behavioural therapy, speech therapy and occupational therapy would be continued.

Baseline investigations would be performed prior to diet initiation, and the diet introduced gradually over a period of 2 weeks. Participants would follow the diet for a period of 6 months, maintaining a dietary log. Weekly telephonic contacts and two monthly physical contacts would be made to ensure compliance and check for any adverse events.

Assessments will be performed at baseline, 3 months and 6 months post intervention in the form of autism severity, behavioral, neurocognitive and sleep assessment.

Eligibility

Primary outcome measure(s)

• To evaluate the efficacy of add-on LGIT vs MAD and GFCF diet along with standard of care in terms of mean reduction in CARS-2 score, at 6 months post intervention, in children with ASD aged 3-8 years. — Baseline and 6 months
  Childhood Autism Rating Score (CARS-2) is a validated tool to assess the severity of ASD based on the core symptoms. It is a questionnaire including 15 items, each being scored on a scale from 1(no symptom) to 4 (severe symptom) at intervals of 0.5, which is completed by interviewing the primary caregiver as well as direct observation of the child. The standard version (CARS-ST) is for children less than 6 years or above 6 years with language impairment or with IQ\<80, while the high functioning version (CARS-HF) is for children older than 6 years who are verbally fluent with IQ\>80. The cutoffs for CARS-ST no autism/remission, mild-moderate and severe autsim respectively are 15-29.5, 30-36 and 37 - 60 respectively. Based on expert consensus from an expert elicitation procedure, a change of \>4.5 points is considered clinically relevant, to distinguish between interventions which are merely statistically significant from those which produce meaningful changes in behavioral outcome.

Trial sites (1)

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