Probiotics to Prevent Relapse After Hospitalization for Bipolar Depression

Study Overview
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Brief Summary
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The purpose of this study is to determine if taking a probiotic supplement versus a placebo will reduce relapse and improve the clinical course among participants who have been hospitalized for bipolar depression.

Official Title
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A Double-Blind Placebo-Controlled Trial of a Probiotic Supplement to Prevent Relapse and Improve the Clinical Course After Hospitalization for Bipolar Depression

Conditions
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Bipolar Depression

Intervention / Treatment
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* Biological: Probiotic Supplement
* Biological: Inert Compound


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-65 (inclusive) Capacity for written informed consent Currently (or within the last 3 weeks) admitted to a Sheppard Pratt inpatient or day hospital program for symptoms of a depressive episode and a diagnosis Bipolar Disorder I or II, most recent episode depressed per Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM-5), the diagnosis of which is confirmed with the Structured Clinical Interview for DSM-5 Disorders (SCID-5) Proficient in the English language Available to come to Sheppard Pratt Towson for study visits after hospital discharge Exclusion Criteria: Depressive symptoms better accounted for by a diagnosis of Major Depressive Disorder, Schizoaffective disorder, Schizophrenia, or disorder(s) other than Bipolar Disorder I or II DSM-5 diagnosis of intellectual disability or comparable diagnosis determined by previous version of the DSM Substance- or medically-induced mood symptoms at time of Visit 1/Baseline visit DSM-5 diagnosis of a moderate or severe substance use disorder, except for caffeine or tobacco, within three months prior to the Visit 1/Baseline visit History of IV drug use Any clinically significant or poorly controlled medical disorder as determined by the principal investigator and/or the study physician (e.g., HIV infection or other immunodeficiency condition, uncontrolled diabetes, congestive heart failure) 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) Pregnant, planning to become pregnant, or breastfeeding during the study period Documented celiac disease Participated in any investigational drug trial in the 30 days prior to the Visit 1/Baseline visit Receipt of Electroconvulsive therapy (ECT) in the 30 days prior to the Visit 1/Baseline visit or planned ECT after hospital discharge

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Probiotic Supplement<br>The probiotic supplement will consist of capsules containing approximately 1 billion (1.0 x 10^9) colony forming units of the probiotic organisms, Lactobacillus rhamnosus LGG® (LGG®) and Bifidobacterium animalis subsp. lactis BB-12® (BB-12®). The capsule, which will be swallowed, is a size 3 opaque, hard, hypromellose capsule. Participants will be asked to take 1 capsule of the probiotic supplement with a meal or with a snack daily for 24 weeks. | Biological: Probiotic Supplement<br>* Probiotic supplement 1 tablet by mouth daily<br>* Other names: Probio-Tec® BG-VCap-6.5;|
| Placebo Comparator: Inert Compound<br>The inert compound placebo looks identical to the probiotic supplement, and participants will be instructed to swallow 1 capsule with a meal or with a snack daily for 24 weeks. | Biological: Inert Compound<br>* Probiotic identical placebo 1 tablet by mouth daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Relapse | Time to relapse defined as time until psychiatric rehospitalization during the study period | Weeks 0 - 24 of study participation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| New Mood Episodes | Number of new mood episodes determined by Structured Clinical Interview for DSM-5 Disorders (SCID-5), an interview using criteria from the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) | Weeks 0 - 24 of study participation | 
| Brief Psychiatric Rating Scale | The Brief Psychiatric Rating Scale (BPRS) will be used to measure the severity of psychiatric symptoms. The BPRS contains 24 items, each rated on a scale from 1 (not present) to 7 (very severe). Total scores range from 24 to 168, and high scores indicate increased symptomatology. | Weeks 0 - 24 of study participation | 
| Young Mania Rating Scale | The Young Mania Rating Scale (YMRS) will be used to measure mania-related symptoms. The YMRS contains 11 items, each rated either on a scale from 0 to 4 or a scale from 0 to 8. Total scores range from 0 to 60, and higher scores indicate increased mania-related symptomatology. | Weeks 0 - 24 of study participation | 
| Montgomery-Åsberg Depression Rating Scale (MADRS) | The Montgomery-Åsberg Depression Rating Scale (MADRS) will be used to measure depression-related symptoms. The MADRS contains 10 items, each rated on a scale from 0 (none or normal) to 6 (most severe). Total scores range from 0 to 60, and higher scores indicate increased depression-related symptomatology. | Weeks 0 - 24 of study participation | 
| Hamilton Depression Rating Scale | The Hamilton Depression Rating Scale (HAM-D) will be used to measure depression-related symptoms. The HAM-D contains 24 items, each rated either on a scale from 0 to 2 or on a scale from 0 to 4. Total scores range from 0 to 76, and higher scores indicate increased depression-related symptomatology. | Weeks 0 - 24 of study participation | 
| Columbia-Suicide Severity Rating Scale | The Columbia-Suicide Severity Rating Scale (C-SSRS) measures suicide attempts and ideation. The C-SSRS is a tool containing one section of items used for assessing the specific type and intensity of suicidal ideation and one section of items used to determine number and type of suicide attempts and actual or potential lethality of the most lethal suicide attempt. The number of items used depends upon participant responses, and higher ratings on specific items indicate either more attempts, more intense ideation, or more lethal behavior. The C-SSRS will be used to determine the occurrence of suicide attempts or ideation. | Weeks 0 - 24 of study participation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bipolar disorder, bipolar depression, depressive episode, probiotic supplement, probiotics, relapse prevention, rehospitalization