Prebiotic Treatment in People With Schizophrenia

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Prebiotic Treatment in People With Schizophrenia

Conditions
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Schizophrenia, Schizoaffective Disorder

Intervention / Treatment
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* Dietary Supplement: Prebiotic
* Dietary Supplement: Placebo Prebiotic


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: DSM-5 diagnosis of schizophrenia or schizoaffective disorder; Age 18-60 years; Considered clinically stable by the treating psychiatrist; Currently treated with an antipsychotic, with no dose changes in last 14 days; Ability to participate in the informed consent process, as determined by a score of 10 or greater on the Evaluation to Sign Consent; BMI ≤ 40 Exclusion Criteria: 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 Organic brain disorder, including cerebrovascular accident; epilepsy; traumatic brain injury, Loss of consciousness (LOC) for more than 30 minutes Intellectual disability Acute antibiotic use Immune therapy within the last three months Prebiotic or probiotic treatment within the last three months Inability to understand English Inability to cooperate with study procedures Pregnant or lactation secondary to pregnancy 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 |