The Effect of Probiotic Supplementation on the Mental Status, Inflammation, and Intestinal Barrier in Major Depressive Disorder Patients Using Gluten-free or Gluten-containing Diet (SANGUT)

Medical University of Lublin

Status: Unknown

Conditions: Depressive Disorder, Major; Depression

Treatments: Combination Product: Probiotic supplementation + gluten-containing diet; Combination Product: Placebo supplementation + gluten-free diet; Combination Product: Placebo supplementation + gluten-containing diet; Combination Product: Probiotic supplementation + gluten-free diet

Study type: Interventional

Funder types: Other

Identifiers

NCT03877393

DS192/2019

Details and patient eligibility

About

More and more evidence confirms the relationship between the gut-brain-microbiota axis and the symptoms of mood disorders. A potential pathway connecting the intestines and the brain in depression is inflammation. Interventions for reducing inflammation and restoring the integrity of the intestinal mucosa are promising approaches in patients with major depressive disorder (MDD). Gut dysbiosis and the diet containing gluten are potential factors may be factors that negatively affect the communication between intestinal and brain. Gluten has a high immunogenic potential and affinity for the intestinal mucosa layer. In patients with an abnormal reaction to gluten, the elimination diet led to improved mood symptoms. However, the relationship between gluten and depression is still poorly understood. Intestinal microbiota can affect the digestion of gluten and reduce its immunogenic potential. Studies have shown that probiotic supplementation has an anti-inflammatory effect, can lead to changes in intestinal permeability and alleviate the symptoms of depression. This evidence supports the need for co-therapy, including the elimination of gluten and the restoration of intestinal eubiosis to reduce inflammation and modulate the gut-brain-microbiota axis. The objective of the SANGUT study is to determine the impact of interventions concerning the gut-brain-microbiota axis (probiotic supplementation, gluten-free diet and their combination) on the mental state, markers of inflammation and markers of intestinal permeability in adult patients with MDD. The study will last 12 weeks and consist of four visits (V): V0 - Screening (Day 0), V1 - Baseline (up to 1 week after Screening), V2 (six weeks after Baseline), V3 - End of the study (12 weeks after Baseline). The main hypothesis is that probiotic supplementation and/or a gluten-free diet will reduce the symptoms of depression, lower the level of inflammatory markers and favourably affect the integrity of the intestinal mucosal barrier.

Enrollment: 120 estimated patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Outpatients aged 18-60 years old;
2. Signed written Informed Consent Form;
3. Meet the DSM-5 criteria for MDD;
4. Body mass index (BMI) ≥18.5 kg/m2 and ≤30 kg/m2;
5. MADRS (Montgomery-Asberg Depression Scale) total score at screening (V0) and at baseline (V1) of 20 points or more (moderate or severe depression);
6. A willingness and motivation to follow the study protocol.

Exclusion criteria

1. Diagnosis of autoimmune, neurological, immunocompromised, thyroid, inflammatory bowel diseases, diabetes, cancers, and/or IgE-dependent allergy;
2. Psychiatric comorbidities (except specific personality disorder) including mental retardation, organic brain dysfunction, or addiction (except nicotine and caffeine);
3. High risk of suicide in the investigator's opinion;
4. An infection one month before the study baseline visit (V1);
5. The use of antibiotics and/or probiotics three months prior to the study;
6. Glucocorticosteroids and/or metformin treatment;
7. Intake of any other drugs which in the investigator' opinion may affect the results of study;
8. Intake of any dietary supplementation (except for vitamin D according to the "Vitamin D supplementation guidelines, 2018") which in the investigator' opinion may affect the results of the study;
9. Changes in a pharmacotherapy and/or psychotherapy of MDD 2 weeks before the trial entry;
10. Electroconvulsive therapy (ECT) 12 months before the trial entry;
11. No specific diet (e.g., elimination, vegan, reduction) and changes in physical activity 4 weeks before the trial entry;
12. Pregnancy or lactation.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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120 participants in 4 patient groups, including a placebo group

PRO-GFD

Experimental group

Description:

Probiotic supplementation + gluten-free diet

Treatment:

Combination Product: Probiotic supplementation + gluten-free diet

PLA-GFD

Placebo Comparator group

Description:

Placebo supplementation + gluten-free diet

Treatment:

Combination Product: Placebo supplementation + gluten-free diet

PRO-GD

Experimental group

Description:

Probiotic supplementation + gluten-containing diet

Treatment:

Combination Product: Probiotic supplementation + gluten-containing diet

PLA-GD

Placebo Comparator group

Description:

Placebo supplementation + gluten-containing diet

Treatment:

Combination Product: Placebo supplementation + gluten-containing diet