A Probiotic Intervention to Prevent Relapse Following Hospitalization for Mania

NCT ID: NCT03383874

Last Updated: 2025-12-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 67 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-06
• Study Completion Date: 2024-09-23

Brief Summary

This will be a 24-week, randomized, double-blind, placebo-controlled trial of adjunctive probiotic therapy in 66 persons hospitalized with a manic or mixed episode. The active study compound will consist of capsules containing approximately 10^9 colony forming units of the probiotic organisms, Lactobacillus GG and Bifidobacteria lactis strain Bb12. The dose has been selected because it has been used safely in other probiotic trials, was well-tolerated by the participants in two previous trials of individuals with schizophrenia or mania, and was utilized in the original trial on which this replication is based. This dose is higher than that available in most commercially-sold health food supplements. Following hospital discharge, participants will be randomized to receive adjunctive probiotic or placebo for a 24 week period. It is anticipated that of the 66 participants randomized, ~50 (75%) will complete the full 24 weeks of the study. The primary outcome is relapse, defined as re-hospitalization (e.g., admission to an inpatient unit) for psychiatric symptoms following a previous hospital discharge by at least 2 weeks. The occurrence of new mood episodes, the severity of psychiatric symptoms, and any changes in cognitive test scores over the course of the study will also be evaluated. Changes in the levels of inflammatory markers as well as changes in gut microbiota will be evaluated at three time intervals over the course of the study.

Detailed Description

Primary Aim 1. To determine if adjunctive probiotic administration can reduce relapse for participants first hospitalized for mania. Hypothesis: Participants receiving adjunctive probiotic microorganisms vs. adjunctive placebo will have a lower rate of relapse as defined by a re-hospitalization (e.g., admission to an inpatient unit) during the 24 week study period.

Secondary Outcomes. The number of new mood episodes, the severity of psychiatric symptoms, and changes in cognitive scores over the 24 week study period will be evaluated.

Exploratory Aim 1. To study the effect of probiotic therapy in lowering the levels of inflammatory markers following an acute episode of mania. Hypothesis: Participants receiving adjunctive probiotic microorganisms vs. adjunctive placebo will have reduced levels of antibodies to casein, gliadin, and the NMDA receptor, and reduced levels of C-Reactive protein and the cytokine TNF alpha following 24 weeks of probiotic therapy.

Exploratory Aim 2. To evaluate changes in the gut microbiota following probiotic administration. Hypothesis: Probiotic administration will enrich the gut microbiota of participants with the given microorganisms and these changes may correlate to changes in the peripheral inflammatory markers being measured.

Conditions

Mania (Neurotic)

Keywords

Probiotic, bipolar disorder, schizoaffective disorder, mania

Study Design

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

Study Groups

Placebo

Participants will receive capsules containing placebo for 24-weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

This placebo is made almost identically to the Probio-Tec but without active microorganisms.

Probiotic-Probio-Tec BG-VCap-6.5

Participants will receive capsules containing approximately 10\^9 colony forming units of the probiotic organisms, Lactobacillus GG and Bifidobacteria lactis strain Bb12 for 24-weeks.

Group Type: EXPERIMENTAL

Probio-Tec BG-VCap-6.5

Intervention Type: COMBINATION_PRODUCT

The product under investigation is a probiotic containing two microorganisms (Lactobacillus rhamnosus, LGG® and Bifidobacterium animalis subsp. lactis, BB-12®, referred to as LGG® and BB-12®, respectively) and is offered commercially as "Probio-Tec BG-VCap-6.5". This composition is formulated to contain a minimum of 1 billion (1.0 x 10\^9) CFU (Colony Forming Units) per dose (capsule), including equal numbers of the two strains; i.e. 0.5 x 10\^9 CFU of each of LGG® and BB-12® at the time of manufacture. The product will be administered orally.

Interventions

Probio-Tec BG-VCap-6.5

The product under investigation is a probiotic containing two microorganisms (Lactobacillus rhamnosus, LGG® and Bifidobacterium animalis subsp. lactis, BB-12®, referred to as LGG® and BB-12®, respectively) and is offered commercially as "Probio-Tec BG-VCap-6.5". This composition is formulated to contain a minimum of 1 billion (1.0 x 10\^9) CFU (Colony Forming Units) per dose (capsule), including equal numbers of the two strains; i.e. 0.5 x 10\^9 CFU of each of LGG® and BB-12® at the time of manufacture. The product will be administered orally.

Intervention Type: COMBINATION_PRODUCT

Placebo

This placebo is made almost identically to the Probio-Tec but without active microorganisms.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Capacity for written informed consent
• Currently (or within the last 3 weeks) admitted to inpatient hospital for symptoms of mania.
• Primary Axis I diagnosis (DSM-5) at time of admission of bipolar I (single manic episode, most recent episode manic, or most recent episode mixed) OR schizoaffective disorder, bipolar type (manic or mixed state).
• Proficient in the English language.
• Available to attend follow-up visits.

Exclusion Criteria

• Substance- or medically-induced symptoms of mania at time of assessment.
• HIV infection or other immunodeficiency condition (such as receiving cancer chemotherapy).
• A serious medical condition that affects brain or cognitive functioning (e.g., epilepsy, serious head injury, concussion involving loss of consciousness, brain tumor, or other neurological disorder). Note that Hepatitis-C is not an exclusion criterion unless the participant has an acute infection.
• Poorly controlled comorbid medical condition.
• Major surgery in the last year.
• History of weight loss surgery.
• Diagnosis of Intellectual Disability or history of severe learning disorder.
• Diagnosis of alcohol or substance use disorder (moderate/severe) according to DSM-5 criteria within the last 3 months, or has a positive drug toxicity screen proximate to the time of recruitment.
• History of IV drug use.
• Participated in any investigational drug trial in the past 30 days.
• Abnormal electrolyte levels.
• AST and ALT > 3 times upper limit of normal.
• Pregnant, breastfeeding, or planning to become pregnant during the study period.
• Documented celiac disease (as such persons should be on a gluten-free diet as this is the standard care). Of note, we are not limiting the study to individuals with elevated levels of gliadin or casein antibodies as we intend to look at these levels as a predictor of response.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Texas Southwestern Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Sherwood Brown, MD, PhD

Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sherwood Brown, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

UT Southwestern Medical Center

Locations

Psychoneuroendocrine Research Program

Dallas, Texas, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

STU 082017-045

Identifier Type: -

Identifier Source: org_study_id