Gut Feeling: Understanding the Mechanisms Underlying the Antidepressant Properties of Probiotics

Major Depressive Disorder Clinical Trial

— PROMEX  

Official title:

Gut Feeling: Understanding the Mechanisms Underlying the Antidepressant Properties of Probiotics

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03893162
• Other study ID #: PROMEX
• Status: Completed
• Phase: N/A
• Start date: July 1, 2019
• Est. completion date: June 30, 2022

Study information

• Verified date: September 2021
• Source: King's College London
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Previous research has suggested that probiotics can improve depressive symptoms in patients with Major Depressive Disorder (MDD), particularly when used in addition to antidepressants. The aim of this exploratory pilot study is to improve the investigator's understanding of the mechanisms underlying these effects. This study will assess the effects of an 8-week double-blind placebo-controlled probiotic intervention on the gut microbiome, inflammatory marker levels, brain activity and neurotransmitter levels in patients with MDD and their relationship to changes in mood. This study will also recruit a group of demographically-matched healthy controls for gut microbiome comparison with the MDD group (non-interventional).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: June 30, 2022
• Est. primary completion date: June 29, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion criteria for MDD participants:

• aged 18-55;
• currently in a depressive episode according to DSM-5 criteria, who are currently on antidepressant treatment but remain symptomatic (HAM-D17 score >13);
• on stable treatment regimen of an approved treatment for at least 6 weeks;
• non-smokers;
• for participants willing to take part in the neuroimaging component: right-handed, no contraindications, non-claustrophobic, weight <126kg;

Exclusion criteria for MDD participants:

• eating disorder, bipolar disorder, schizophrenia or psychotic symptoms;
• substance dependence in the past year, except for caffeine;
• active suicidal ideation;
• use of probiotic supplements in the past 2 weeks, or regular use of a probiotic;
• use of antibiotics in the past 12 weeks;
• history of allergic reaction to any of the components of BioKult;
• history of history of a systemic medical illness;
• current presence of significant GI problems or disease or history of major GI surgery;
• pregnancy or breastfeeding;
• following a dietary regimen unrepresentative of the general population (e.g. fasting or following a specific diet);
• regular/current use of antacids, proton pump inhibitors, laxatives, antidiarrheals;

Inclusion criteria for Healthy Volunteers:

• Aged 18-55;
• No current or historic presence of depression, other psychiatric disorder or substance dependence
• No history of a systemic medical illness;
• No family history of psychiatric disorder;
• Non-smoker;
• Not used probiotic supplements in the past 2 weeks, nor regular use of a probiotic;
• Not used antibiotics in the past 12 weeks;
• No current presence of gastrointestinal disease, or history of major GI surgery;
• No reported regular/current use of antacids, proton pump inhibitors, laxatives, antidiarrheals;
• pregnancy or breastfeeding;
• not currently following a dietary regimen or dietary restrictions unrepresentative of the general population (e.g. fasting or following a specific diet);

Related Conditions & MeSH terms

• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

Dietary Supplement:
• Multi-strain probiotic
The intervention in this study is a multi-strain probiotic which contains: Bacillus subtilis, Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium infantis, Bifidobacterium longum, Lactobacillus acidophilus, Lactobacillus delbrueckii ssp. bulgaricus, Lactobacillus casei, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus helveticus, Lactobacillus salivarius, Lactococcus lactis ssp. lactis, Streptococcus thermophilus. Each capsule contains minimum 2 billion live microorganisms per capsule, equivalent to 10 billion live microorganisms per gram.

Other:
• Placebo
Visually identical capsules in identical packaging containing no active bacteria.

Locations

Country	Name	City	State
United Kingdom	King's College London	London

Sponsors (1)

Lead Sponsor	Collaborator
King's College London

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	gut microbiota in MDD	species diversity and abundance at the level of organisational taxonomic units (OTUs) will be measured with 16S ribosomal RNA (rRNA) sequencing	baseline
Primary	differences in gut microbiota between MDD and healthy volunteers	species diversity and abundance at the level of OTUs will be measured with 16SrRNA-based sequencing and compared between the two groups	baseline
Primary	gut microbiota changes in MDD following probiotic intervention and their correlation to change in depressive symptoms	species diversity and abundance at the level of OTUs will be measured with 16SrRNA-based sequencing and depressive symptoms will be measured with the Inventory of Depressive Symptomatology Self-Report (IDS-SR) and the Hamilton Depression Rating Scale (HAM-D17)	change from baseline to week 8
Secondary	Neurotransmitters	levels of glutamate and gamma-aminobutyric acid (GABA) will be measured with Magnetic Resonance Imaging (MRS)	change from baseline to week 8
Secondary	Blood	levels of tumor necrosis factor (TNF-a), interleukins IL-1ß, IL-6, IL-17, and C-reactive protein (CRP) will be measured	change from baseline to week 8
Secondary	Brain activity	measured with functional magnetic resonance imaging (fMRI)	change from baseline to week 8