Clinical trial NCT05717946: The Influence of Probiotic Supplementation on the Severity of Anxiety and Depressive Symptoms, as Well as the Function and Composition of Gut Microbiota, Metabolic, Inflammation, and Oxidative Stress Markers in Patients With Depression
Official title: The Influence of Probiotic Supplementation on the Severity of Anxiety and Depressive Symptoms, as Well as the Function and Composition of Gut Microbiota, Metabolic, Inflammation, and Oxidative Stress Markers in Patients With Depression
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Depression
Anxiety
Keywords: probiotics
depression
anxiety
microbiome
metabolism
Lead sponsor: Medical University of Lodz
Sponsor class: OTHER
First posted: 2023-02-08
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective, randomized, placebo-controlled, and double-blind trial
Primary purpose: TREATMENT

Brief summary: The aim of this study is to gather empirical evidence which will enable to evaluate the impact of probiotic supplementation on the severity of anxiety and depressive symptoms, function, and composition of gut microbiota, metabolic parameters, inflammation, and oxidative stress markers in patients with diagnosed depressive disorders.

The designed study will be prospective, randomized, placebo-controlled, and double-blind. The intervention period will last 8 weeks for each patient. The study will be conducted on 100 patients in total, who will be randomly divided into two groups, consisting of 50 patients each.

Patients included in Group I (PRO-D) will receive one capsule daily containing a probiotic mixture at a daily dose of 3×109 colony-forming units (CFU). The probiotic will be composed of two bacteria strains: Lactobacillus helveticus Rosell®-52, Bifidobacterium longum Rosell®-175, and excipients: potato starch, magnesium stearate, and the capsule shell, made of hydroxypropylmethylcellulose.

Patients included in Group II (PLC-D) will receive daily the same capsule, containing only excipients: potato starch, maltodextrin, and the capsule shell. The color, smell, and taste of the placebo will not be different from those included in the probiotic capsule.

Patients will be considered compliant if they consume \>= 80% of the supplements.

The primary outcome measures will be the severity of depressive anxiety and stress symptoms assessed with Montgomery-Åsberg Depression Rating Scale (MADRS) and the Depression, Anxiety, Stress Scale (DASS) with subscales scores, the quality of life level assessed with the WHOQOL-BREF instrument. The secondary outcomes measures will include: blood pressure (BP), body mass index (BMI) and waist circumference (WC) measures, fasting glucose (fGlc), HDL cholesterol (HDL-C), triglycerides (TG), white blood cells count (WBC), neutrofiles, serum levels of C-reactive protein (CRP), the level of faecal SCFAs, faecal microbiota α-diversity and the level of oxidative stress parameters (total antioxidant capacity (TAC) and malondialdehyde (MDA)) in the blood serum.


Eligibility criteria: Inclusion Criteria:

1. Depressive disorders diagnosed according to ICD-11,
2. Age between 18 - 70 years,
3. MADRS score \>=13,
4. Antidepressant and antianxiety medications not changed 3 weeks prior to the recruitment visit.

Exclusion Criteria:

1. Pregnancy,
2. An infection/vaccination and/or treatment with antibiotics in the previous 4 weeks,
3. Supplementation with pro- or prebiotics in the previous 4 weeks,
4. Having a diagnosis of autoimmune, serious immunocompromised, inflammatory bowel diseases, cancer, IgE-dependent allergy, or severe kidney failure in the previous 4 weeks,
5. body mass index (BMI)\> 35,
6. glomerular filtration rate (GFR)\< 30 ml/min/1,72 m2,
7. unstable thyroid dysfunction (TSH \< 0,27 or \> 4,2 μIU/ml) in the previous 4 weeks,
8. Psychiatric comorbidities (except specific personality disorder, additional specific anxiety disorder, and caffeine, and nicotine addiction),
9. Regular treatment (more than 3 days a week) with PPIs, metformin, laxatives, systemic steroids, or NSAIDs in the previous 4 weeks,
10. Significant change in dietary pattern in the previous 4 weeks,
11. Significant change in daily physical activity or extreme sports activity in the previous 4 weeks,
12. Significant change in dietary supplementation in the previous 4 weeks,
13. Significant change in smoking pattern in the previous 4 weeks,
14. High risk of suicide,
15. Is participating in, or has recently participated in, another research study involving an intervention that may alter outcomes of interest to this study,
16. Any other condition or situation which, in the view of investigators, would affect the compliance or safety of the individual taking part.

Reasons for the participant to be discontinued from the study:

1. Withdrawal of informed consent,
2. An infection/vaccination and/or treatment with antibiotics during the trial,
3. Consuming any other than studied probiotics during the trial,
4. Lack of compliance with the probiotic supplementation,
5. Any change in the drug regimen during the study,
6. Exclusion criteria found after enrolment,
7. Any serious adverse event during the trial.

Primary outcomes:
measure: Montgomery-Åsberg Depression Rating Scale (MADRS)
timeFrame: 8 weeks
measure: Depression, Anxiety, Stress Scale (DASS21)
timeFrame: 8 weeks
measure: The World Health Organization quality of life-BREF questionnaire (WHOQOL-BREF)
timeFrame: 8 weeks
Secondary outcomes:
measure: Blood pressure (BP)
timeFrame: 8 weeks
measure: Body mass index (BMI)
timeFrame: 8 weeks
measure: Waist circumference (WC)
timeFrame: 8 weeks
measure: White blood cells count (WBC)
timeFrame: 8 weeks
measure: Neutrofiles count
timeFrame: 8 weeks
measure: Serum levels of C-reactive protein (CRP)
timeFrame: 8 weeks
measure: The level of faecal short-chain fatty acids (SCFAs)
timeFrame: 8 weeks
measure: Faecal microbiota α-diversity
timeFrame: 8 weeks
measure: Total antioxidant capacity (TAC) in the blood serum
timeFrame: 8 weeks
measure: Malondialdehyde (MDA) level in the blood serum
timeFrame: 8 weeks
measure: Fasting glucose (fGlc)
timeFrame: 8 weeks
measure: HDL cholesterol (HDL-C)
timeFrame: 8 weeks
measure: Triglycerides (TG)
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Łódź
country: Poland
facility: Central Teaching Hospital, Medical University of Lodz
Study officials:
affiliation: Medical University of Lodz
name: Dominik Strzelecki, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: