The Safety and Effectiveness of Probiotic Supplementation on Bipolar Depression

Study Overview
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Brief Summary
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This is an 8-week randomized, double-blind placebo-controlled proof of concept study assessing the combination of a mood stabilizer + Align in the treatment of participants with a bipolar depressive episode. The study has two treatment arms: mood stabilizer plus placebo and mood stabilizer plus Align. The dose of mood stabilizer will be in accordance with clinical practice guidelines and the dose for Align will be 1 capsule per day as per appropriate product dosing.

Detailed Description
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Depression has emerged as the major challenge for short- and long-term management of bipolar disorder; new treatments are needed to help control this illness. Studies indicate that probiotics in the stomach improves mood and reduces anxiety symptoms lending further support to the notion that probiotic bacteria positively influence emotional states. We propose to evaluate the effectiveness of the combination of mood stabilizer and Align, a probiotic as compared to mood stabilizer monotherapy. The primary goal of this feasibility study is to determine the safety and tolerability of Align as an add on to accepted monotherapy treatment in BD. Secondary Objective:1)To evaluate the effectiveness of the combination of mood stabilizer + Align compared to mood stabilizer monotherapy in treatment of BD. 2) to determine if Align +mood stabilizer combination will reduce anxiety symptoms. An 8-week randomized, double-blind placebo-controlled proof of concept study assessing the combination a mood stabilizer + Align in the treatment of patients with an bipolar depressive episode. The study has two treatment arms: mood stabilizer + placebo and mood stabilizer + Align. Participants will be assessed & administered study scales at screening, baseline & weeks 2,4,6 and 8. the dose for mood stabilizer will be in accordance with clinical practice guidelines and Align - 1 capsule/day.

Official Title
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The Safety and Effectiveness of Probiotic Supplementation on Bipolar Depression: a Proof of Concept Randomized Controlled Trial

Conditions
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Bipolar Depression

Intervention / Treatment
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* Dietary Supplement: Bifidobacterium infantis
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed of the nature of the study and have agreed to and are able to read, review, and sign the informed consent form. The informed consent document will be written in English, therefore the volunteer must have the ability to read and communicate in English Male and Female participants 18 - 65 years of age ,inclusive, at the time of screening Demonstrates a diagnosis of bipolar depression (type I or II) according to the Mini International Neuropsychiatric interview (MINI) Is not hospitalized or institutionalized (outpatient) at the time of screening Have been on a stable (unchanged) and adequate dose of one of the permissible medications for at least 8 weeks prior to screening (lithium, valproate/divalproex, carbamazepine, lamotrigine, quetiapine/quetiapine XR, olanzapine, or risperidone) Demonstrates a maximum HAM-D score of 24 at screening and baseline visits Female participants Must: Not be breast feeding Not be pregnant or seeking to get pregnant during the course of this study. Be menopausal or using an acceptable method of birth control (implants, injectables, combined oral contraceptives, IUDs, sexual abstinence or a vasectomized partner) Exclusion Criteria: Demonstrates or reports a history of any of the DSM-IV criteria for classification of substance abuse/dependence disorders in the past year. Demonstrates the presence of active eating disorders, schizophrenia or schizoaffective disorder Demonstrates current psychotic symptoms Demonstrates a Young Mania Rating Scale (YMRS) score of >12 at screening Demonstrates active suicidality based on the C-SSR scale Reports using any potent cytochrome P450 inhibitors (such as chloramphenicol, antifungal agents) during the 14 days prior to screening Reports a history of electroconvulsive therapy (ECT) during the 90 days prior to screening Reports using Align or any other probiotic supplement within the last year prior to screening Reports a history of allergic response(s) to components of Align (such as Bifidobacterioum), or any other related drug. Reports a presence or history of any medical conditions that would affect drug pharmacokinetics (gastrointestinal conditions such as chroris or colitus). Reports a history of any immunocompromising condition (such as HIV, lymphoma, patients undergoing long-term corticosteroid treatment) Currently experiencing nausea, fever, vomiting, bloody diarrhea or severe abdominal pain Reports use of other natural health products (in addition to probiotics) that affect depression (such as St. Johns Wart, Tryptophan) within the last 6 months prior to screening Reports frequent consumption of foods rich in / enriched with probiotics (e.g. yoghurt, drinks, e.t.c).

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
Interventional Model Description: Participants are randomized to receive either ALIGN (probiotic) or Placebo
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Bifidobacterium infantis<br>Bifidobacterium infantis (Align) 10.00 million cfu capsule once daily | Dietary Supplement: Bifidobacterium infantis<br>* Probiotic supplement<br>* Other names: ALIGN;|
| Placebo Comparator: Placebo<br>Placebo capsule once daily | Other: Placebo<br>* Placebo capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety and tolerability of Align | Tolerability will be assessed using the Toronto Side Effect Scale (TSES). It is a 32-item instrument that is designed to establish incidence, frequency, and severity of central nervous system (CNS), gastrointestinal (GI), and sexual side effects. We will also assess the proportion of participants withdrawing from study due to inadequate control of depressive symptoms or treatment emergent mania | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The effectiveness of the combination of mood stabilizer + Align | This will be assessed through the change in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score from baseline to the final visit (week 8) | 8 weeks | 
| evaluate the combination of mood stabilizer + Align as compared to mood stabilizer monotherapy for participants with bipolar depression with respect to anxiety symptoms and global function/overall improvement | Anxiety symptoms will be assessed by looking at the mean change in the State and Trait Anxiety Index (STAI) total score, quality of life will be assessed with the World Health Organization Quality of Life (WHO-QOL) scale and global functioning will be accessed via mean change in the following: Sheehan Disability Scale (SDS) score, the clinical global impressions (CGI) severity of illness score, the CGI-Improvement scale and the CGI Participant Assessment. All measures will be evaluated looking at change from baseline to week 8 | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CGI, Bipolar, Depression, Probiotic, ALIGN, HAMD, STAI, YMRS, SDS, WHOQOL-BREF, C-SSRS, TSES