Ketogenic Diet Therapy for Autism Spectrum Disorder

NCT02477904 | Completed DMC

• 1 other identifier: HON1403
• Study Type: interventional
• Target: 119
• Locations: 1 country
• Sites: 1

Brief Summary

This study will assess the effectiveness of the ketogenic diet (high-fat, low-carbohydrate, and moderate protein) in treating autism spectrum disorder (ASD). Three study groups will be comprised of children (2-21 years of age) based on whether or not they have ASD and receive the ketogenic diet - ASD/ketogenic diet, ASD/non-ketogenic diet, and non-ASD/non-ketogenic diet.

Conditions

Autism Spectrum Disorder

Keywords

Autism; Autism Spectrum Disorder; Ketogenic Diet; Biochemical Profiles

Outcome Measures

Primary Outcomes (1)

• Change from baseline in core symptoms of ASD

  Assess core autistic symptoms through review/analysis of responses to the following measurement instruments: Autism Diagnostic Observation Schedule - Second Edition (ADOS-2); Asperger Syndrome Diagnostic Scale (ASDS); Childhood Autism Rating Scale (CARS-2); Gilliam Autism Rating Scale (GARS-3); Social Responsiveness Scale - Second Edition (SRS-2); Diagnostic and Statistical Manual IV Text Revision (DSM-IV-TR) and DSM-V ASD criteria; standardized intelligence tests (if available, administered by child's school); and Vanderbilt ADHD Diagnostic Teacher Rating Scale Forms (Vanderbilt).

  Pre- and post-ketogenic diet intervention (at baseline, and after three and six months on the ketogenic diet)

Secondary Outcomes (7)

• Change from baseline in the number of medications used for ASD management

  Pre- and post-ketogenic diet intervention (at baseline, and after three and six months on the ketogenic diet)

• Change from baseline in the dosage of medications used for ASD management

  Pre- and post-ketogenic diet intervention (at baseline, and after three and six months on the ketogenic diet)

• Change from baseline in the number of lab tests ordered for ASD management

  Pre- and post-ketogenic diet intervention (at baseline, and after three and six months on the ketogenic diet)

• Change from baseline in the number of emergency room or hospital visits for ASD management

  Pre- and post-ketogenic diet intervention (at baseline, and after three and six months on the ketogenic diet)

• Change from baseline in subject/family satisfaction with the ketogenic diet

  Pre- and post-ketogenic diet intervention (at baseline, and after three and six months on the ketogenic diet)

Other Outcomes (1)

• Possible effects of the ketogenic diet

  Post-ketogenic diet intervention

Study Arms (3)

ASD/KD

EXPERIMENTAL

Children (2-21 years of age) diagnosed with autism spectrum disorder (ASD) will receive the ketogenic diet (KD) intervention.

Other: Ketogenic Diet

ASD/non-KD

ACTIVE COMPARATOR

Children (2-21 years of age) diagnosed with autism spectrum disorder (ASD) will not receive the ketogenic diet (KD) intervention.

Other: Ketogenic Diet

non-ASD/non-KD

ACTIVE COMPARATOR

Typically developing children (2-21 years of age) diagnosed as not having autism spectrum disorder (ASD) will not receive the ketogenic diet (KD) intervention.

Other: Ketogenic Diet

Interventions

Ketogenic Diet OTHER

Dietary

Also known as: Classic Ketogenic Diet, Shriner's Ketogenic Diet, Non-Ketogenic Diet

ASD/KD; ASD/non-KD; non-ASD/non-KD

Eligibility Criteria

• Age: 2 Years - 21 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Ages 2-21 years.
• Primary diagnosis of autism spectrum disorder.
• Parent/legal guardian and child able to read or understand English, and able/willing to provide informed consent/assent.
• Females of childbearing potential must have a negative pregnancy test result and agree to use a medically acceptable method of contraception throughout the entire study period and for 30 days after the last dose of study drug - childbearing potential is defined a girls who are \> Tanner stage 2 and urine pregnancy tests are acceptable.

You may not qualify if:

• Known cardiac disorder including arrhythmias or hypertension.
• BMI \< 3rd%ile.
• Carnitine deficiency (primary).
• Carnitine palmitoyltransferase (CPT) I or II deficiency.
• Carnitine translocase deficiency.
• Beta-oxidation defects - medium-chain acyl dehydrogenase deficiency (MCAD), long-chain acyl dehydrogenase deficiency (LCAD), short-chain acyld dehydrogenase deficiency (SCAD), long-chain 3-hydroxyacyl-coenzyme A (CoA) deficiency, and medium-chain 3-hydroxyacyl-CoA deficiency.
• Pyruvate carboxylase deficiency.
• Porphyria.
• Inability to maintain adequate nutrition.
• Patient or caregiver non-compliance.

Sponsors & Collaborators

• Shriners Hospitals for Children: lead
• University of Hawaii: collaborator

Study Sites (1)

Shriners Hospitals for Children - Honolulu

Honolulu, Hawaii, 96826-1099, United States

Location

Related Publications (20)

• Stafstrom CE, Rho JM. The ketogenic diet as a treatment paradigm for diverse neurological disorders. Front Pharmacol. 2012 Apr 9;3:59. doi: 10.3389/fphar.2012.00059. eCollection 2012.

  PMID: 22509165 BACKGROUND

• Evangeliou A, Vlachonikolis I, Mihailidou H, Spilioti M, Skarpalezou A, Makaronas N, Prokopiou A, Christodoulou P, Liapi-Adamidou G, Helidonis E, Sbyrakis S, Smeitink J. Application of a ketogenic diet in children with autistic behavior: pilot study. J Child Neurol. 2003 Feb;18(2):113-8. doi: 10.1177/08830738030180020501.

  PMID: 12693778 BACKGROUND

• Mantis JG, Fritz CL, Marsh J, Heinrichs SC, Seyfried TN. Improvement in motor and exploratory behavior in Rett syndrome mice with restricted ketogenic and standard diets. Epilepsy Behav. 2009 Jun;15(2):133-41. doi: 10.1016/j.yebeh.2009.02.038. Epub 2009 Feb 26.

  PMID: 19249385 BACKGROUND

• Ruskin DN, Svedova J, Cote JL, Sandau U, Rho JM, Kawamura M Jr, Boison D, Masino SA. Ketogenic diet improves core symptoms of autism in BTBR mice. PLoS One. 2013 Jun 5;8(6):e65021. doi: 10.1371/journal.pone.0065021. Print 2013.

  PMID: 23755170 BACKGROUND

• Niederhofer H. Association of attention-deficit/hyperactivity disorder and celiac disease: a brief report. Prim Care Companion CNS Disord. 2011;13(3):PCC.10br01104. doi: 10.4088/PCC.10br01104.

  PMID: 21977364 BACKGROUND

• Cryan JF, Dinan TG. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci. 2012 Oct;13(10):701-12. doi: 10.1038/nrn3346. Epub 2012 Sep 12.

  PMID: 22968153 BACKGROUND

• Harris SL, Handleman JS. Age and IQ at intake as predictors of placement for young children with autism: a four- to six-year follow-up. J Autism Dev Disord. 2000 Apr;30(2):137-42. doi: 10.1023/a:1005459606120.

  PMID: 10832778 BACKGROUND

• Mulle JG, Sharp WG, Cubells JF. The gut microbiome: a new frontier in autism research. Curr Psychiatry Rep. 2013 Feb;15(2):337. doi: 10.1007/s11920-012-0337-0.

  PMID: 23307560 BACKGROUND

• Wang Y, Kasper LH. The role of microbiome in central nervous system disorders. Brain Behav Immun. 2014 May;38:1-12. doi: 10.1016/j.bbi.2013.12.015. Epub 2013 Dec 25.

  PMID: 24370461 BACKGROUND

• Adams JB, Johansen LJ, Powell LD, Quig D, Rubin RA. Gastrointestinal flora and gastrointestinal status in children with autism--comparisons to typical children and correlation with autism severity. BMC Gastroenterol. 2011 Mar 16;11:22. doi: 10.1186/1471-230X-11-22.

  PMID: 21410934 BACKGROUND

• Kang DW, Park JG, Ilhan ZE, Wallstrom G, Labaer J, Adams JB, Krajmalnik-Brown R. Reduced incidence of Prevotella and other fermenters in intestinal microflora of autistic children. PLoS One. 2013 Jul 3;8(7):e68322. doi: 10.1371/journal.pone.0068322. Print 2013.

  PMID: 23844187 BACKGROUND

• Ming X, Stein TP, Barnes V, Rhodes N, Guo L. Metabolic perturbance in autism spectrum disorders: a metabolomics study. J Proteome Res. 2012 Dec 7;11(12):5856-62. doi: 10.1021/pr300910n. Epub 2012 Nov 9.

  PMID: 23106572 BACKGROUND

• Wang L, Christophersen CT, Sorich MJ, Gerber JP, Angley MT, Conlon MA. Elevated fecal short chain fatty acid and ammonia concentrations in children with autism spectrum disorder. Dig Dis Sci. 2012 Aug;57(8):2096-102. doi: 10.1007/s10620-012-2167-7. Epub 2012 Apr 26.

  PMID: 22535281 BACKGROUND

• Wang L, Christophersen CT, Sorich MJ, Gerber JP, Angley MT, Conlon MA. Increased abundance of Sutterella spp. and Ruminococcus torques in feces of children with autism spectrum disorder. Mol Autism. 2013 Nov 4;4(1):42. doi: 10.1186/2040-2392-4-42.

  PMID: 24188502 BACKGROUND

• Williams BL, Hornig M, Parekh T, Lipkin WI. Application of novel PCR-based methods for detection, quantitation, and phylogenetic characterization of Sutterella species in intestinal biopsy samples from children with autism and gastrointestinal disturbances. mBio. 2012 Jan 10;3(1):e00261-11. doi: 10.1128/mBio.00261-11. Print 2012.

  PMID: 22233678 BACKGROUND

• Yap IK, Angley M, Veselkov KA, Holmes E, Lindon JC, Nicholson JK. Urinary metabolic phenotyping differentiates children with autism from their unaffected siblings and age-matched controls. J Proteome Res. 2010 Jun 4;9(6):2996-3004. doi: 10.1021/pr901188e.

  PMID: 20337404 BACKGROUND

• De Angelis M, Piccolo M, Vannini L, Siragusa S, De Giacomo A, Serrazzanetti DI, Cristofori F, Guerzoni ME, Gobbetti M, Francavilla R. Fecal microbiota and metabolome of children with autism and pervasive developmental disorder not otherwise specified. PLoS One. 2013 Oct 9;8(10):e76993. doi: 10.1371/journal.pone.0076993. eCollection 2013.

  PMID: 24130822 BACKGROUND

• Hsiao EY, McBride SW, Hsien S, Sharon G, Hyde ER, McCue T, Codelli JA, Chow J, Reisman SE, Petrosino JF, Patterson PH, Mazmanian SK. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell. 2013 Dec 19;155(7):1451-63. doi: 10.1016/j.cell.2013.11.024. Epub 2013 Dec 5.

  PMID: 24315484 BACKGROUND

• Sandler RH, Finegold SM, Bolte ER, Buchanan CP, Maxwell AP, Vaisanen ML, Nelson MN, Wexler HM. Short-term benefit from oral vancomycin treatment of regressive-onset autism. J Child Neurol. 2000 Jul;15(7):429-35. doi: 10.1177/088307380001500701.

  PMID: 10921511 BACKGROUND

• Allan NP, Yamamoto BY, Kunihiro BP, Nunokawa CKL, Rubas NC, Wells RK, Umeda L, Phankitnirundorn K, Torres A, Peres R, Takahashi E, Maunakea AK. Ketogenic Diet Induced Shifts in the Gut Microbiome Associate with Changes to Inflammatory Cytokines and Brain-Related miRNAs in Children with Autism Spectrum Disorder. Nutrients. 2024 May 7;16(10):1401. doi: 10.3390/nu16101401.

  PMID: 38794639 DERIVED

MeSH Terms

Conditions

Autism Spectrum Disorder; Autistic Disorder

Interventions

Diet, Ketogenic

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Diet, Carbohydrate-Restricted; Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Officials

• Ryan W Lee, MD

  Shriners Hospitals for Children, Honolulu

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director - Neurodevelopmental Clinic, Research

Study Record Dates

• First Submitted: June 16, 2015
• First Posted: June 23, 2015
• Study Start: March 1, 2015
• Primary Completion: April 28, 2017
• Study Completion: April 28, 2017
• Last Updated: September 20, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)