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

NCT07797725 | Not Yet Recruiting DMC

• 1 other identifier: 32178
• Study Type: interventional
• Target: 123
• Locations: 1 country
• Sites: 1

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

Conditions

Autism Spectrum Disorder

Keywords

low glycemic index diet, modified Atkins diet, gluten free casein free diet, Autsim Spectrum Disorder

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

  Baseline and 6 months

Secondary Outcomes (5)

• To evaluate the efficacy of add-on MAD vs GFCF diet in addition to standard of care in terms of mean reduction of CARS-2 score, at 6 months post intervention in children with ASD aged 3-8 years

  Baseline and 6 months

• To compare the change in the cognitive ability as measured by DQ (VABS) , SQ (VSMS) and IQ (MISIC) in children receiving add on LGIT vs MAD and GFCF along with standard of care in children with ASD aged 3-8 years at 3 months and 6 months post initiation

  Baseline, 3 months and 6 months

• To compare the quantitative reduction in symptoms of co-morbidities like inattention, hyperactivity, aggression (CBCL) and sleep related abnormalities (CHSQ-SF) in children with ASD in all three arms after follow up for 3 and 6 months.

  Baseline, 3 months and 6 months

• To assess the compliance in children aged 3-8 years with ASD receiving add-on LGIT, MAD and GFCF diet with standard of care

  From enrolment to 6 months

• To assess the adverse effect profile in children aged 3 - 8 years with ASD receiving add-on LGIT, MAD and GFCF diet with standard of care.

  From enrolment to 6 months

Study Arms (3)

Low glycemic index diet with standard of care

EXPERIMENTAL

Exclusion of high glycemic index foods (with Glycemic index \>50), along with standard of care

Other: Low glycemic index diet with standard of care

Modified Atkins diet with standard of care

ACTIVE COMPARATOR

Modified Atkins diet: A less restrictive version of the ketogenic diet, with standard of care

Other: Modified Atkins diet with standard of care

Gluten free casein free diet with standard of care

ACTIVE COMPARATOR

Exclusion of gluten and casein containing foods, along with standard of care

Other: Gluten free casein free diet with standard of care

Interventions

Low glycemic index diet with standard of care OTHER

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.

Also known as: LGIT with Standard of Care

Low glycemic index diet with standard of care

Modified Atkins diet with standard of care OTHER

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.

Also known as: MAD with Standard of Care

Modified Atkins diet with standard of care

Gluten free casein free diet with standard of care OTHER

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.

Also known as: GFCF diet with Standard of Care

Gluten free casein free diet with standard of care

Eligibility Criteria

• Age: 3 Years - 8 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Children aged 3 to 8 years diagnosed with ASD according to DSM -V criteria

You may not qualify if:

• ASD in remission : DSM V criteria fulfilled only historically and/or current CARS-2 score \<30
• Genetic/acquired metabolic disorders including fatty acid oxidation defects, pyruvate carboxylase deficiency, porphyria, diabetes mellitus, dyslipidemia
• Presence of kidney stones
• Children with failure to thrive/underweight/stunting, poor oral intake
• Gastroesophageal reflux
• Chronic systemic illness: renal/cardiac/hepatic/lung disease, chronic metabolic acidosis, malabsorption
• Changes in antipsychotic medications over the last 1 month
• Associated epilepsy
• Pre-existing food fads
• Food allergies: to gluten and/or casein, celiac disease
• Those who have been on Ketogenic diet/ Modified Atkins diet/ Low Glycemic Index Diet / Gluten free and/or Casein free diet in the last 6 months
• Refusal of consent

Sponsors & Collaborators

• All India Institute of Medical Sciences: lead

Study Sites (1)

All India Institute of Medical Sciences, New Delhi

New Delhi, New Delhi, 110029, India

Location

Related Publications (14)

• ICMR-NIN Expert Group on Nutrient Requirement for Indians, Recommended Dietary Allowances (RDA) and Estimated Average Requirements (EAR) - 2020.

  BACKGROUND

• Manideepthi, S Gulati (2026). Efficacy of Modified Atkins Diet as add-on therapy in comparison with standard of care in children with Autism Spectrum Disorder: A Randomized Controlled Trial. (Unpublished DM thesis). All India Institute of Medical Sciences, New Delhi.

  BACKGROUND

• Muzykewicz DA, Lyczkowski DA, Memon N, Conant KD, Pfeifer HH, Thiele EA. Efficacy, safety, and tolerability of the low glycemic index treatment in pediatric epilepsy. Epilepsia. 2009 May;50(5):1118-26. doi: 10.1111/j.1528-1167.2008.01959.x. Epub 2009 Feb 12.

  PMID: 19220406 BACKGROUND

• Chen W, Kossoff EH. Long-term follow-up of children treated with the modified Atkins diet. J Child Neurol. 2012 Jun;27(6):754-8. doi: 10.1177/0883073812441062. Epub 2012 Apr 24.

  PMID: 22532541 BACKGROUND

• S. Gulati, K. L. Gupta, S. Ojha et al. Role of Gluten-Free-Casein-Free (GFCF) Diet in Children with Autism Spectrum Disorder: A Randomized Controlled Trial https://insar.confex.com/insar/2025/meetingapp.cgi/Paper/50829

  BACKGROUND

• Quan L, Xu X, Cui Y, Han H, Hendren RL, Zhao L, You X. A systematic review and meta-analysis of the benefits of a gluten-free diet and/or casein-free diet for children with autism spectrum disorder. Nutr Rev. 2022 Apr 8;80(5):1237-1246. doi: 10.1093/nutrit/nuab073.

  PMID: 34617108 BACKGROUND

• Keller A, Rimestad ML, Friis Rohde J, Holm Petersen B, Bruun Korfitsen C, Tarp S, Briciet Lauritsen M, Handel MN. The Effect of a Combined Gluten- and Casein-Free Diet on Children and Adolescents with Autism Spectrum Disorders: A Systematic Review and Meta-Analysis. Nutrients. 2021 Jan 30;13(2):470. doi: 10.3390/nu13020470.

  PMID: 33573238 BACKGROUND

• Kossoff EH, Zupec-Kania BA, Auvin S, Ballaban-Gil KR, Christina Bergqvist AG, Blackford R, Buchhalter JR, Caraballo RH, Cross JH, Dahlin MG, Donner EJ, Guzel O, Jehle RS, Klepper J, Kang HC, Lambrechts DA, Liu YMC, Nathan JK, Nordli DR Jr, Pfeifer HH, Rho JM, Scheffer IE, Sharma S, Stafstrom CE, Thiele EA, Turner Z, Vaccarezza MM, van der Louw EJTM, Veggiotti P, Wheless JW, Wirrell EC; Charlie Foundation; Matthew's Friends; Practice Committee of the Child Neurology Society. Optimal clinical management of children receiving dietary therapies for epilepsy: Updated recommendations of the International Ketogenic Diet Study Group. Epilepsia Open. 2018 May 21;3(2):175-192. doi: 10.1002/epi4.12225. eCollection 2018 Jun.

  PMID: 29881797 BACKGROUND

• Schrickel A, Groeneweg J, Dekeyster E. Exploring the potential of the ketogenic diet in autism spectrum disorder: metabolic, genetic, and therapeutic insights. Metab Brain Dis. 2025 Jan 8;40(1):94. doi: 10.1007/s11011-024-01518-1.

  PMID: 39776279 BACKGROUND

• Lakshminarayanan K, Agarawal A, Panda PK, Sinha R, Tripathi M, Pandey RM, Gulati S. Efficacy of low glycemic index diet therapy (LGIT) in children aged 2-8 years with drug-resistant epilepsy: A randomized controlled trial. Epilepsy Res. 2021 Mar;171:106574. doi: 10.1016/j.eplepsyres.2021.106574. Epub 2021 Feb 9.

  PMID: 33582533 BACKGROUND

• Currais A, Farrokhi C, Dargusch R, Goujon-Svrzic M, Maher P. Dietary glycemic index modulates the behavioral and biochemical abnormalities associated with autism spectrum disorder. Mol Psychiatry. 2016 Mar;21(3):426-36. doi: 10.1038/mp.2015.64. Epub 2015 Jun 9.

  PMID: 26055422 BACKGROUND

• Jurek L, Baltazar M, Gulati S, Novakovic N, Nunez M, Oakley J, O'Hagan A. Response (minimum clinically relevant change) in ASD symptoms after an intervention according to CARS-2: consensus from an expert elicitation procedure. Eur Child Adolesc Psychiatry. 2022 Aug;31(8):1-10. doi: 10.1007/s00787-021-01772-z. Epub 2021 Apr 7.

  PMID: 33825947 BACKGROUND

• Anand V, Gulati S, Agarwala A, Kamila G, Mahesan A, Sondhi V, Gupta KL, Chakrabarty B, Jauhari P, Panda PK, Pandey RM. Comparison of efficacy of low glycemic index treatment and modified Atkins diet among children with drug-resistant epilepsy: A randomized non-inferiority trial. Epilepsia. 2025 May;66(5):1550-1559. doi: 10.1111/epi.18292. Epub 2025 Jan 30.

  PMID: 39887979 BACKGROUND

• El-Rashidy O, El-Baz F, El-Gendy Y, Khalaf R, Reda D, Saad K. Ketogenic diet versus gluten free casein free diet in autistic children: a case-control study. Metab Brain Dis. 2017 Dec;32(6):1935-1941. doi: 10.1007/s11011-017-0088-z. Epub 2017 Aug 14.

  PMID: 28808808 BACKGROUND

MeSH Terms

Conditions

Autism Spectrum Disorder

Interventions

Standard of Care; mycophenolic adenine dinucleotide

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Sheffali Gulati

  All India Institute of Medical Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sheffali Gulati

CONTACT

01126594679; sheffaligulati@gmail.com

Sheffali Gulati

CONTACT

9810386847; sheffaligulati1@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr Sheffali Gulati

Study Record Dates

• First Submitted: August 27, 2026
• First Posted: September 1, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2028
• Last Updated: September 1, 2026

Record last verified: 2026-08

Locations

IN (1)