Prebiotic Treatment in People With Schizophrenia - Pilot Study

NCT ID: NCT03617783

Last Updated: 2023-06-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-18
• Study Completion Date: 2022-04-05

Brief Summary

The purpose of this study is to examine changes in serum butyrate levels with the prebiotic: Prebiotin (12g/day), an oligofructose-enriched inulin (OEI); the effect of OEI on the composition of the gastrointestinal microbiota in people with schizophrenia; and the relationship of the composition of the gut microbiota to various clinical, cognitive, and neuroimaging variables.

Detailed Description

Over the past 10 years, considerable evidence has emerged from animal studies to suggest that the gut microbiome has significant effects on brain development and behavior, with bidirectional communication between the enteric nervous system, gut and the central nervous system (CNS) (Diaz Heijtz et al, 2011; Douglas-Escobar et al, 2013; Dinan et al, 2014). The gut microbiota have been shown to: a) produce multiple neurotransmitters, including gamma-aminobutyric acid (GABA), dopamine, norepinepherine, and serotonin, and may regulate CNS levels of these neurotransmitters; b) modulate brain development through the regulation of synaptogenesis; and c) modulate the levels of stress hormones during brain development, which may affect stress response and anxiety behavior (Diaz Heijtz et al, 2011; Dinan et al, 2014; Sudo et al, 2004; O'Mahony et al, 2015). Moreover, the gut microbiota effects the production of neurotrophins, including brain-derived neurotrophic factor (BDNF), which plays a significant role in neurogenesis and synaptic plasticity (Sudo et al, 2004; Nemani et al, 2015).

The gut microbiome may also affect brain development and function through its regulation of immune system function, which is mediated, in part, through the production of short-chain fatty acids (SCFA). There are three major SCFAs: butyrate, propionate, and acetate. Butyrate is of particular interest, since it plays a key role in maintaining gut homeostasis and epithelial integrity: butyrate is the primary energy source for intestinal colonocytes; and, of the three SCFAs, butyrate appears to have the most pronounced effects on immune system function and may exert its effects directly through immune pathways and indirectly through the maintenance of the integrity of the intestinal-blood barrier (Hamer et al, 2008; Louis et al, 2010; Brahe et al, 2013; Vital et al, 2014). The intestinal-blood barrier restricts the entrance of toxins, pathogens and antigens into the blood circulation; thus, increased permeability could lead to the entrance of substances and subsequent immune response.

The multiple effects of the gut microbiome on brain development and behavior, suggest that alterations in the gut microbiome may occur in schizophrenia and play a part in the pathophysiology of the disorder. The increased prevalence of gastrointestinal disorders in schizophrenia; the association of infections, including infections with Toxoplasma gondii, which can induce intestinal inflammation, with the risk for the development of schizophrenia; and evidence of increased gut permeability provide further indirect evidence for disruption of the gut microbiome in this disorder (Dinan et al, 2014; Nemani et al, 2015; Severance et al, 2012; Severance et al, 2014). Although a number of studies have been conducted in other neuropsychiatric disorders, including autism (Parracho et al, 2005; Tomova et al, 2015), which demonstrate altered bacterial composition of the gut microbiome, there is only one published study of the microbiome in schizophrenia. Yolken and colleagues examined the oropharyngeal microbiome in people with schizophrenia, and found that there were increased levels of the bacteriophage, Lactobacillus phage phiadh, genome in the schizophrenia group, which were correlated with co-occurring immunological disorders (Yolken et al, 2015). There is one published study of gut microbiota in schizophrenia. Shen and colleagues found a significant reduction in butyrate producers in people with schizophrenia compared to healthy controls (Shen et al. Schiz Res, https://doi.org/10.1016/j.schres.2018.01.002).

The purpose of this study is to examine changes in serum butyrate levels with the prebiotic: Prebiotin (12g/day), an oligofructose-enriched inulin (OEI); the effect of OEI on the composition of the gastrointestinal microbiota in people with schizophrenia; and the relationship of the composition of the gut microbiota to various clinical, cognitive, and neuroimaging variables.

Conditions

Schizophrenia; Schizoaffective Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: QUADRUPLE

Study Groups

Prebiotin

Group Type: ACTIVE_COMPARATOR

Prebiotin

Intervention Type: DRUG

Prebiotin (12g/day), an oligofructose-enriched inulin (OEI)

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

placebo-OEI

Interventions

Prebiotin

Prebiotin (12g/day), an oligofructose-enriched inulin (OEI)

Intervention Type: DRUG

Placebo

placebo-OEI

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. DSM-IV-TR /DSM 5 diagnosis of schizophrenia or schizoaffective disorder;

2. Age 18-60 years

3. Clinically stable as determined by opinion of treating clinician

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 ≤ 35

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. Antibiotic or immune therapy within the last three months

5. Prebiotic or probiotic treatment within the last three months

6. Inability to understand English

7. Inability to cooperate with study procedures

8. Pregnant or lactating women secondary to pregnancy

9. Meet DSM-5 criteria for alcohol or substance use disorders (except Tobacco Use Disorder) within last 3 months

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Maryland, Baltimore

OTHER

Sponsor Role: lead

Responsible Party

Robert Buchanan

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Maryland Psychiatric Research Center (MPRC) Treatment Research Program (TRP)

Catonsville, Maryland, United States

Countries

United States

References

Buchanan RW, Werkheiser AE, Michel H, Zaranski J, Glassman M, Adams HA, Vyas G, Blatt F, Pilli NR, Pan Y, Chen S, Fraser CM, Kelly DL, Kane MA. Prebiotic Treatment in People With Schizophrenia. J Clin Psychopharmacol. 2024 Sep-Oct 01;44(5):457-461. doi: 10.1097/JCP.0000000000001899. Epub 2024 Aug 16.

Reference Type: DERIVED

PMID: 39146178 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

HP-00081820

Identifier Type: -

Identifier Source: org_study_id