Confirmatory Efficacy Trial of a Gluten-Free Diet in a Subgroup of Persons With Schizophrenia Who Have High Levels of IgG Anti-Gliadin Antibodies (AGA IG)

Confirmatory Double-Blind Placebo-Controlled Efficacy Trial of a Gluten-Free Diet in a Subgroup of Persons With Schizophrenia Who Have High Levels of IgG Anti-Gliadin Antibodies (AGA IG)

This study purpose is to conduct a confirmatory double-blind randomized controlled trial in an inpatient setting of the effects of a tightly controlled gluten-free diet (GFD) to improve negative symptoms in people with schizophrenia or schizoaffective disorder who have antibodies to gliadin (AGA IgG). As part of the project investigators will also confirm outcomes such as cognitive symptoms, changes in peripheral and central inflammation as well as gut/blood brain barrier permeability.

Study Overview

• Status: Recruiting
• Conditions: Schizophrenia; Schizo Affective Disorder; Gluten Sensitivity
• Intervention / Treatment: Other: Gluten Flour in Protein Shake; Other: Rice Flour in Protein Shake

Detailed Description

This study is a randomized double blind clinical trial being funded by NIMH. Investigators will need to enroll 40 cases with AGA IgG positivity in order to present a powered and convincing result about the efficacy of gluten withdrawal in the subpopulation of persons with schizophrenia with elevated AGA IgG levels. Investigators will recruit a minimum 50 to ensure they are well powered without question, and to account for dropouts. Investigators will use a battery of measures of peripheral and central inflammation as well as gut permeability at baseline and endpoint to confirm the relationship of these outcomes to changes in AGA IgG and symptom changes in the clinical trial. Investigators will test negative symptoms as a primary outcome but will test changes in other symptom domains such as positive symptoms. After the completion of the 5 week confirmatory study, investigators will discharge participants and follow them for 8 weeks in their own environment to test the maintenance of the effect following the stringent GFD, and provide education on gluten free shopping, cooking and eating.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ann Keanrs, MS; Phone Number: 410-402-6854; Email: akearns@mprc.umaryland.edu

Study Locations

• United States
  • Maryland
    • Catonsville, Maryland, United States, 21228
      • Recruiting
      • Maryland Psychiatric Research Center (MPRC) Outpatient Research Program (ORP); the MPRC Treatment Research Program (TRP)
      • Contact: AnnMarie Kearns, BS; Phone Number: 410-402-6854; Email: akearns@mprc.umaryland.edu
      • Contact: Stephanie Feldman, MSW; Phone Number: 410-402-6885; Email: sfeldman@mprc.umaryland.edu
      • Principal Investigator: Deanna L Kelly, Pharm.D., BCPP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. DSM-IV/DSM 5 diagnosis of schizophrenia or schizoaffective disorder
2. Positive for antibodies to gliadin (IgG > 20 U)
3. SANS total score ≥ 20 and the affective flattening or alogia global item ≥ 3
4. Age 18- 64 years
5. Same antipsychotic for at least 4 weeks
6. Ability to consent determined by a score of 10 or greater on the Evaluation to Sign Consent.

Exclusion Criteria:

1. Persons already on gluten free diets
2. Positivity to tissue transglutaminase (tTg) antibodies or known history of Celiac Disease
3. Pregnant or lactating females
4. Medical condition whose pathology or treatment could alter the presentation or treatment of schizophrenia or significantly increase the risk associated with the proposed treatment protocol
5. Meets DSM-5 criteria for alcohol or substance use disorder (other than nicotine) within the last month

6. Gluten ataxia, as measured by the Brief Ataxia Rating Scale

   Additional exclusion for those participating in optional imaging component:

7. Non-removable ferromagnetic metal on or within the body
8. Current claustrophobia
9. Inability to lie supine for 1.5 hours

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Gluten; 30 grams of gluten flour daily in protein shake	Other: Gluten Flour in Protein Shake; 15 Grams Gluten Flour BID
Placebo Comparator: Placebo; 30 grams of rice flour daily in protein shake	Other: Rice Flour in Protein Shake; 15 Grams Rice Flour BID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Negative symptom change as defined by difference in Scale for the Assessment of Negative Symptoms (SANS) score	This will be measured by the difference in Scale for the Assessment of Negative Symptoms (SANS) score from baseline to week 5.	5 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in cognitive function as measured by change in MATRICS Consensus Cognitive Battery (MCCB)	This will be measured by the difference in MATRICS Consensus Cognitive Battery (MCCB) scores from baseline to week 5	5 weeks

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore

Publications and helpful links

Helpful Links

• Maryland Psychiatric Research Center

Study record dates

Study Major Dates

• Study Start (Actual): July 10, 2017
• Primary Completion (Estimated): March 30, 2024
• Study Completion (Estimated): July 30, 2025

Study Registration Dates

• First Submitted: June 7, 2017
• First Submitted That Met QC Criteria: June 8, 2017
• First Posted (Actual): June 12, 2017

Study Record Updates

• Last Update Posted (Estimated): February 1, 2024
• Last Update Submitted That Met QC Criteria: January 31, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Psychotic Disorders; Mood Disorders
• Other Study ID Numbers: HP-00075175

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