Clinical Evaluation of the Antidepressant Effect of the Use of Probiotics in Bipolar Disorder

Sponsor

University of Sao Paulo (Other)

Overall Status

Recruiting

CT.gov ID

NCT05762887

Collaborator

Baszucki Brain Research Fund (Other), Milken Institute (Other)

Enrollment

Location

Arms

12.7

Anticipated Duration (Months)

6.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Bipolar Disorder (BD) is highly incapacitating and associated with premature mortality. Depressive symptoms and episodes are the most frequent cause of disability in subjects with BD and over half of patients do not respond adequately to approved treatments for this condition, showing the need for new classes of treatments to complement current pharmacotherapy. Previous studies demonstrated that the intestinal flora have potential positive or negative effects on the Central Nervous System and suggest that adding specific strains of bacteria to people's diet may have antidepressant properties.The study proposes to evaluate the clinical benefit of adding probiotics to pharmacological treatments for bipolar depression. This will be a study with 84 subjects (42 receiving probiotics and 42 placebo). The research team in this department has focused especially on non-pharmacological treatments for bipolar disorder (psychotherapy, nutrition and exercise) and is multidisciplinary in scope with psychiatrists, psychologists, nurses, physiotherapists and nutritionists participating in research projects.

Condition or Disease	Intervention/Treatment	Phase
Bipolar Disorder	Other: Probiotic Group Other: Placebo Group	N/A

Detailed Description

It will test, in a proof-of-concept study, the antidepressant efficacy of adjunctive administration of probiotics in bipolar depression and evaluate potential inflammatory and metabolic markers associated with response to treatment. With this objective, 84 individuals with bipolar disorder type I or type II presenting subsyndromal depressive symptoms or a major depressive episode will be recruited. The study design lasts 12 weeks and is expected to last two years.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

84 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

A Randomized, Double-Blind, Placebo-controlledA Randomized, Double-Blind, Placebo-controlled

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

All blind clinical assessments will be done by Psychiatrists, members of the University of São Paulo (USP) Bipolar Research Program managed by Michelle Flores. In this study, the intervention will be double-blind: All participants will receive the exact same pill, whether placebo or intervention, with equal packaging-manufacturing.

Primary Purpose:

Other

Official Title:

Clinical Evaluation of the Antidepressant Effect of the Use of Probiotics in Bipolar Disorder and Possible Mediating Effects of Systemic and Intestinal Inflammatory Markers in the Microbiota

Actual Study Start Date :

Jan 9, 2023

Anticipated Primary Completion Date :

Aug 30, 2023

Anticipated Study Completion Date :

Jan 30, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Probiotic group In addition to the usual medication treatment for bipolar disorder, as per the main international guidelines for the treatment of bipolar disorder, subjects will receive food supplementation with a probiotic formulation twice daily. We will use Pendulum, a probiotic formulation patented in the United States associated with a prebiotic, inulin and magnesium stearate.	Other: Probiotic Group The 84 participants will participate in a randomized, double-blind, placebo-controlled trial in two arms. The probiotic group will consist of 42 patients. These patients will be recruited from the USP Bipolar Disorder Program. This program has an outpatient clinic that offers free medical care to a population of different ethnic groups, with the majority of subjects coming from the middle and lower social classes.
Placebo Comparator: Placebo Group In addition to the usual drug treatment for bipolar disorder, following the main international guidelines for the treatment of bipolar disorder, the subjects will receive, twice a day, together with meals, food supplementation containing inulin and magnesium stearate.	Other: Placebo Group The 84 participants will participate in a randomized, double-blind, placebo-controlled trial in two arms. The placebo group will consist of 42 patients. These patients will be recruited from the USP Bipolar Disorder Program. This program has an outpatient clinic that offers free medical care to a population of different ethnic groups, with the majority of subjects coming from the middle and lower social classes.

Arm

Intervention/Treatment

Experimental: Probiotic group

In addition to the usual medication treatment for bipolar disorder, as per the main international guidelines for the treatment of bipolar disorder, subjects will receive food supplementation with a probiotic formulation twice daily. We will use Pendulum, a probiotic formulation patented in the United States associated with a prebiotic, inulin and magnesium stearate.

Other: Probiotic Group

The 84 participants will participate in a randomized, double-blind, placebo-controlled trial in two arms. The probiotic group will consist of 42 patients. These patients will be recruited from the USP Bipolar Disorder Program. This program has an outpatient clinic that offers free medical care to a population of different ethnic groups, with the majority of subjects coming from the middle and lower social classes.

Placebo Comparator: Placebo Group

In addition to the usual drug treatment for bipolar disorder, following the main international guidelines for the treatment of bipolar disorder, the subjects will receive, twice a day, together with meals, food supplementation containing inulin and magnesium stearate.

Other: Placebo Group

The 84 participants will participate in a randomized, double-blind, placebo-controlled trial in two arms. The placebo group will consist of 42 patients. These patients will be recruited from the USP Bipolar Disorder Program. This program has an outpatient clinic that offers free medical care to a population of different ethnic groups, with the majority of subjects coming from the middle and lower social classes.

Outcome Measures

Primary Outcome Measures

Outcome [12 weeks]
The Montgomery-Asberg Depression Rating Scale (MADRS) will be used in order to evaluate the reduction of depressive symptoms. Response to treatment at week-12 will be defined as ≥ 50% reduction in total MADRS total score from baseline. Remission will be defined as MADRS total score ≤ 12.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

BD type I or type II, according to the use of Mini Internacional Neuropsychiatric Interview (MINI)
Score on the Young Mania Rating Scale (YMRS) < 8
Score on the Montgomery-Asberg Depression Rating Scale (MADRS) > 8
Be receiving major guideline-approved treatments for bipolar depression for at least 4 weeks

Exclusion Criteria:

Pregnant or lactating women
Substance or alcohol dependence
Patients on prolonged antibiotic therapy, immunosuppressive therapies
A recent introduction of antidepressants in the last 15 days
Use of another probiotic, either in the form of food, sachets, capsules and others

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Sao Paulo	São Paulo	Sao Paulo	Brazil	05403010

Sponsors and Collaborators

University of Sao Paulo
Baszucki Brain Research Fund
Milken Institute

Investigators

Principal Investigator: Beny lafer, PhD, University of Sao Paulo

Study Documents (Full-Text)

None provided.

More Information

Publications

Ho P, Ross DA. More Than a Gut Feeling: The Implications of the Gut Microbiota in Psychiatry. Biol Psychiatry. 2017 Mar 1;81(5):e35-e37. doi: 10.1016/j.biopsych.2016.12.018. No abstract available.

Responsible Party:

Beny Lafer, Principal Investigator, University of Sao Paulo

ClinicalTrials.gov Identifier:

NCT05762887

Other Study ID Numbers:

U1111-1280-7625

First Posted:

Mar 10, 2023

Last Update Posted:

Mar 14, 2023

Last Verified:

Mar 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Yes

Additional relevant MeSH terms:

Bipolar Disorder

Study Results

No Results Posted as of Mar 14, 2023