Clinical trial NCT03877393: 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
Official title: A 12-week, Randomized, Double-blind, and Placebo-controlled Study Evaluating 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Depressive Disorder, Major
Depression
Keywords: Probiotics; dietary supplements
Diet, Gluten-Free
Inflammation
Gastrointestinal Microbiome
Intestinal mucosal permeability
Gut-brain axis
Gut permeability
EEG functional connectivity
Cortisol
Hypothalamic-pituitary-adrenal axis
Cognitive function
Lead sponsor: Medical University of Lublin
Sponsor class: OTHER
Collaborators: name: Sanprobi Sp. z o.o., Sp. k., Szczecin, Poland
First posted: 2019-03-15
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, double-blind, and placebo-controlled study
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: The changes in Montgomery-Åsberg Depression Rating Scale(MADRS) total score to measure the severity of depression symptoms
timeFrame: from the date of randomization until the end of the study up to 12 weeks
measure: The changes in Beck Depression Inventory (BDI) total score to measure the severity of depression symptoms
timeFrame: from the date of randomization until the end of the study up to 12 weeks
measure: The changes in Symptom Checklist-90 (SCL-90) total score to measure the severity of psychopathological impairment
timeFrame: from the date of randomization until the end of the study up to 12 weeks
measure: The changes in the 36-Item Short Form Survey (SF-36) total score to measure the quality of life
timeFrame: from the date of randomization until the end of the study up to 12 weeks
measure: The changes in the Perceived Stress Scale (PSS-10) total score to measure the stress levels
timeFrame: from the date of randomization until the end of the study up to 12 weeks
Secondary outcomes:
measure: Changes in serum levels of high-specific C-reactive protein (hs-CRP)
timeFrame: from the date of randomization until the end of the study up to 12 weeks
measure: Changes in serum levels of interleukin 6 (Il-6)
timeFrame: from the date of randomization until the end of the study up to 12 weeks
measure: Changes in serum levels of interleukin 1beta (Il-1beta)
timeFrame: from the date of randomization until the end of the study up to 12 weeks
measure: Changes in serum levels of tumor necrosis factor alpha (TNF-alpha)
timeFrame: from the date of randomization until the end of the study up to 12 weeks
measure: Changes in serum levels of anti-tissue transglutaminase (anti-TG2) IgG antibodies
timeFrame: from the date of randomization until the end of the study up to 12 weeks
measure: Changes in serum levels of anti-gliadin (anti-AGA) IgG antibodies
timeFrame: from the date of randomization until the end of the study up to 12 weeks
measure: Changes in serum levels of anti-gliadin (anti-AGA) IgA antibodies
timeFrame: from the date of randomization until the end of the study up to 12 weeks
measure: Changes in serum levels of intestinal fatty acid-binding protein (I-FABP/FABP-2)
timeFrame: from the date of randomization until the end of the study up to 12 weeks
measure: Changes in serum levels of lipopolysaccharide biding protein (LBP)
timeFrame: from the date of randomization until the end of the study up to 12 weeks
measure: Changes in serum levels of total cholesterol
timeFrame: from the date of randomization until the end of the study up to 12 weeks
measure: Changes in serum levels of low-density lipoprotein (LDL) cholesterol
timeFrame: from the date of randomization until the end of the study up to 12 weeks
measure: Changes in serum levels of high-density lipoprotein (HDL) cholesterol
timeFrame: from the date of randomization until the end of the study up to 12 weeks
measure: Changes in serum levels of triglycerides (TG)
timeFrame: from the date of randomization until the end of the study up to 12 weeks
measure: Changes in serum levels of glucose
timeFrame: from the date of randomization until the end of the study up to 12 weeks
measure: Changes in serum levels of insulin
timeFrame: from the date of randomization until the end of the study up to 12 weeks
measure: Changes in serum levels of cortisol
timeFrame: from the date of randomization until the end of the study up to 12 weeks
measure: Changes in serum levels of alanine aminotransferase (ALT)
timeFrame: from the date of randomization until the end of the study up to 12 weeks
measure: Changes in serum levels of aspartate aminotransferase (AST)
timeFrame: from the date of randomization until the end of the study up to 12 weeks
measure: Changes in diversity in microbial community in a single sample (alpha-diversity)
timeFrame: from the date of randomization until the end of the study up to 12 weeks
measure: Changes in diversity in microbial community between samples (beta-diversity)
timeFrame: from the date of randomization until the end of the study up to 12 weeks
measure: Changes in stool short-chain fatty acids (SCFAs) levels
timeFrame: from the date of randomization until the end of the study up to 12 weeks
measure: Changes in electroencephalography (EEG) analysis to assess the functional connectivity (FC)
timeFrame: from the date of randomization until the end of the study up to 12 weeks
measure: Changes in Gastrointestinal Symptom Rating Scale (GSRS) total score to measure intensity of experienced gastrointestinal symptoms
timeFrame: from the date of randomization until the end of the study up to 12 weeks
measure: Changes in Trail Making Test (TMT) to measure the cognitive abilities
timeFrame: from the date of randomization until the end of the study up to 12 weeks
Other outcomes:
Locations:
city: Lublin
country: Poland
facility: 1st Department of Psychiatry, Psychotherapy and Early Intervention, Medical University of Lublin
Study officials:
References:
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citation: Karakula-Juchnowicz H, Galecka M, Rog J, Bartnicka A, Lukaszewicz Z, Krukow P, Morylowska-Topolska J, Skonieczna-Zydecka K, Krajka T, Jonak K, Juchnowicz D. The Food-Specific Serum IgG Reactivity in Major Depressive Disorder Patients, Irritable Bowel Syndrome Patients and Healthy Controls. Nutrients. 2018 Apr 28;10(5):548. doi: 10.3390/nu10050548.
citation: Skonieczna-Zydecka K, Marlicz W, Misera A, Koulaouzidis A, Loniewski I. Microbiome-The Missing Link in the Gut-Brain Axis: Focus on Its Role in Gastrointestinal and Mental Health. J Clin Med. 2018 Dec 7;7(12):521. doi: 10.3390/jcm7120521.
citation: Karakula-Juchnowicz H, Rog J, Juchnowicz D, Loniewski I, Skonieczna-Zydecka K, Krukow P, Futyma-Jedrzejewska M, Kaczmarczyk M. The study evaluating 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 study): a 12-week, randomized, double-blind, and placebo-controlled clinical study protocol. Nutr J. 2019 Aug 31;18(1):50. doi: 10.1186/s12937-019-0475-x.