Prebiotic Treatment in People With Schizophrenia (FOCIS)

The proposed project is based on the observation that schizophrenia is characterized by a chronic pro-inflammatory state, which contributes to the severity of a number of the clinical manifestations of the illness, including cognitive impairments, the treatment of which represents a critically important unmet therapeutic need.

Study Overview

• Status: Recruiting
• Conditions: Schizophrenia; Schizoaffective Disorder
• Intervention / Treatment: Dietary supplement: Prebiotic; Dietary supplement: Placebo Prebiotic

Detailed Description

The investigators hypothesize that the level of inflammation in people with schizophrenia can be reduced through the use of the prebiotic: Prebiotin®, an oligofructose-enriched inulin (OEI), to stimulate the activity of butyrate-producing bacteria and increase the production of butyrate, which has multiple anti-inflammatory properties. The investigators will confirm the effect of prebiotic administration on the biological signature and examine whether increased serum butyrate levels are associated with changes in cognitive performance (primary specific aim), symptoms, and metabolic measures; and the extent to which these associations are mediated by the anti-inflammatory properties of butyrate, including the ability of butyrate to decrease gut permeability and inhibit the production of pro-inflammatory cytokines, and/or changes in gut microbiota composition.

In a sample of participants with a DSM-5 diagnosis of schizophrenia or schizoaffective disorder, the investigators will conduct a 12-week, double-blind, placebo-controlled, randomized clinical trial to confirm the effect of prebiotic administration on the biological signature and examine whether increased serum butyrate levels are associated with changes in cognitive performance, symptoms, and metabolic measures; and the extent to which these associations are mediated by the anti-inflammatory properties of butyrate, including the ability of butyrate to decrease gut permeability and inhibit the production of pro-inflammatory cytokines, and/or changes in gut microbiota composition.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sarah Caimona; Phone Number: 410-402-6883; Email: scaimona@som.umaryland.edu
• Study Contact Backup: Name: Jennifer Zaranski, MA; Phone Number: 410-402-6060; Email: jzaranski@som.umaryland.edu

Study Locations

• United States
  • Maryland
    • Catonsville, Maryland, United States, 21228
      • Recruiting
      • Maryland Psyciatric Research Center
      • Contact: Sarah Caimona; Phone Number: 410-402-6883; Email: scaimona@som.umaryland.edu
      • Principal Investigator: Robert Buchanan, M.D.
      • Contact: Jennifer Zaranski, MA; Phone Number: 410-402-6060; Email: jzaranski@som.umaryland.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. DSM-5 diagnosis of schizophrenia or schizoaffective disorder;
2. Age 18-60 years;
3. Considered clinically stable by the treating psychiatrist;
4. Currently treated with an antipsychotic, with no dose changes in last 14 days;
5. Ability to participate in the informed consent process, as determined by a score of 10 or greater on the Evaluation to Sign Consent;
6. BMI ≤ 40

Exclusion Criteria:

1. Gastrointestinal disorders, including, but not limited to Crohn's Disease, Irritable Bowel Syndrome, Celiac Disease, whose pathology or treatment could alter the presentation or treatment of schizophrenia or significantly increase the risk associated with the proposed treatment protocol
2. Organic brain disorder, including cerebrovascular accident; epilepsy; traumatic brain injury, Loss of consciousness (LOC) for more than 30 minutes
3. Intellectual disability
4. Acute antibiotic use
5. Immune therapy within the last three months
6. Prebiotic or probiotic treatment within the last three months
7. Inability to understand English
8. Inability to cooperate with study procedures
9. Pregnant or lactation secondary to pregnancy
10. Participants who meet DSM 5 criteria for alcohol or substance misuse (except caffeine and nicotine) within the last 3 months will be excluded. Participants who meet DSM 5 criteria for marijuana misuse - mild will be included in the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active Study Med; Participants randomized to active study medication will mix 4g of powder prebiotic with water, 3 times a day for 12 weeks.	Dietary supplement: Prebiotic; Prebiotin® is a fine, white to slightly yellow powder, which is mixed into water and has a slightly sweet taste.; Other Names: Prebiotin®
Placebo Comparator: Placebo; Participants randomized to active study medication will mix 4g of powder placebo with water, 3 times a day for 12 weeks.	Dietary supplement: Placebo Prebiotic; Placebo prebiotic mixed into water; Other Names: maltodextrin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in serum butyrate levels	Number of participants with an increase in serum butyrate levels at 12 weeks.	12 weeks
Cognition	Number of participants with an increase in MCCB composite score at 12 weeks.	12 weeks
Incidence of Side Effects	Number of participants with an increased incidence of side effects at 12 weeks.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Affective Symptoms	Number of participants with an increase in affective symptoms at 12 weeks, measured by the Calgary Depression Scale (CDS).	12 weeks
Change in Positive Symptoms	Number of participants with an increase in positive symptoms at 12 weeks, measured by the Brief Psychiatric Rating Scale (BPRS).	12 weeks
Change in Negative Symptoms	Number of participants with an increase in negative symptoms at 12 weeks, measured by the • Scale for the Assessment of Negative Symptoms (SANS).	12 weeks
Changes in Serum Measurements	Number of participants with an increase in fasting levels of serum glucose, triglycerides, and/or cholesterol at 12 weeks.	12 weeks
Effects of Gut Composition	Number of participants with an increase in cytokine, gut permeability, or gut microbiota composition levels at 12 weeks.	12 weeks

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore
• Collaborators: National Center for Complementary and Integrative Health (NCCIH)
• Investigators: Principal Investigator: Robert Buchanan, M.D., University of Maryland, Baltimore

Study record dates

Study Major Dates

• Study Start (Actual): January 25, 2023
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: August 30, 2022
• First Submitted That Met QC Criteria: September 1, 2022
• First Posted (Actual): September 2, 2022

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Psychotic Disorders
• Other Study ID Numbers: HP-00102648; R61AT009990 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No