The Gluten-Casein-free Diet in Children With Autism: A Clinical Results of the Ophthalmic and Behavioral Manifestations

Effect of Gluten-free, Casein-free Diet in Children With Autism

To evaluate the efficacy of eight weeks of GFCF in children with ASD on autistic symptoms and ophthalmic findings such as corneal reflex, interpupillary distance (IPD) and pupil size.

Study Overview

• Status: Completed
• Conditions: Autism Spectrum Disorder; Ophthalmic Abnormalities
• Intervention / Treatment: Behavioral: Gluten Free Casein Free Diet

Detailed Description

Autism spectrum disorder (ASD) is a common condition. ASD is a heritable illness characterized by early-onset differences in interaction, communication, sensory atypicality, and stereotyped behaviors. Recent studies suggest a link between elimination diets and severity of autistic behaviors. The etiology of ASD has been still uncertain. Therefore, elucidating the underlying pathology may assist in risk assessment and facilitate process management. Non-harmful and existing evidence for the diet's benefits in ASD must be elucidated.

Primary Study Objective:

To assess the effect of a GFCF diet on variables autism index, stereotyped behaviors, communication, social interaction associated with ASD.

The pupillary response can be utilized to anticipate neurological and physiological activities under the surface. Changes in light trigger the pupil response, which adjusts the amount of brightness falling on the retina by instinctively constricting or dilating the pupil. Atypical pupil size has been linked to abnormal autonomic function in people with ASD. Disturbances in autonomic functions may also lead to differences in the corneal reflex. This study aimed to obtain more data on the behavioral symptoms and ophthalmic measurements of gluten-free casein-free (GFCF) on ASD. In addition, normal development children and children with autism may differ in facial morphology. This study also evaluates the effect of GFCF diet on IPD distance.

Secondary Objectives:

To assess the role of GFCF diet in the manifestation of opthalmic measurements such as pupil size, corneal reflex and IPD.

30 children with ASD were enrolled in a 8-weeks prospective GFCF diet treatment study. In the study, a single group was evaluated with measurements before and after dietary intervention.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Turkey
  • İstanbul, Turkey, 34672
    • Uskudar University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Informed consent / Assent, as applicable must be signed prior to executing any study related procedure
• Children, male or female, 2 to 11 years old (inclusive)
• Confirmed diagnosis of ASD according to the DSM-IV Symptom Checklist
• Ability to maintain a gluten- and casein-free diet during the study

Exclusion Criteria:

• Cardiovascular, psychiatric, autoimmune, cancer, etc. children with secondary different disease
• Children with any drug use
• Children currently receiving treatment with any alternative medical methods (eg.hyperbaric).
• Children with a diagnosis of celiac disease
• Children who have received any dietary treatment before

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Gluten Free Casein Free Diet; Foods containing gluten (pasta, bread, etc.), casein (unfermented dairy products), and their disguised sources have been eliminated from the nutrition program. Also, packaged foods (chocolate, crackers, etc.) containing additives such as artificial preservatives, food coloring, and sweeteners that create a tendency to consume in children were avoided from the nutrition program. Goat milk contains type A2 casein, and most of the casein is digested in fermented dairy products. In order to increase calcium intake, the consumption of some foods (dill, kale, spinach, chard, arugula, broccoli, parsley, legumes, nuts, tahini, etc.) has been increased. Elimination was done gradually, considering nervousness, anxiety, etc., due to the effects of opioid mechanisms of action and gastrointestinal system symptoms.

Behavioral: Gluten Free Casein Free Diet; Thirty children with autism were evaluated before the diet (Pre-Test) and after 8 weeks of dietary intervention (Post-Test).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gilliam Autism Rating Scale 2 (GARS-2)	Based on DSM-IV autism diagnostic criteria, GARS-2 is a behavior checklist for children and teenagers aged 3 to 22. The three subscales of the scale are communication, social interaction, and stereotypical behavior. Each subscale contains 14 items that are scored on a four-point scale (0: Never observed, 1: Rarely observed, 2: Sometimes observed, 3: Often observed). The total score obtained from the scale is converted into standard scores, and an OBI score is obtained. An OBI score of 85 and above indicates a high probability of having ASD, a score between 70-84 indicates a medium probability, and a score of 69 and below indicates a low probability.	8 weeks
Weight (kg)	Body weight was measured in kilograms.	8 weeks
Body mass index	Body mass index (BMI)=weight/(height)^2	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The pupil measurements	The measurements of both groups were taken from a distance of 1 meter with a binocular photo refractometer under the same conditions, without cycloplegia. Plusoptix® A09 an measure a pupil size of 4.0-8.0 mm in 0.1 mm steps. Eccentric photorefraction is used as a measurement basis. The device provides convenience in terms of pediatric evaluation with its remarkable features. The pupil measurements were performed by an ophthalmologist in the outpatient clinical unit. The brightness level in the room was controlled via the lux meter application. Pupil size (mm) was measured at least three times after each participant was left in a room with a light level of 8 cd/m2 for 2 minutes. The average value of 3 consecutive consistent measurements was recorded.	8 weeks

Collaborators and Investigators

• Sponsor: Uskudar University

Study record dates

Study Major Dates

• Study Start (Actual): November 26, 2020
• Primary Completion (Actual): March 14, 2022
• Study Completion (Actual): January 18, 2023

Study Registration Dates

• First Submitted: April 26, 2023
• First Submitted That Met QC Criteria: May 5, 2023
• First Posted (Actual): May 8, 2023

Study Record Updates

• Last Update Posted (Actual): May 8, 2023
• Last Update Submitted That Met QC Criteria: May 5, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: gluten free casein free diet
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autistic Disorder; Autism Spectrum Disorder; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Caseins
• Other Study ID Numbers: UskudarUGFCFAUTISM

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No