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

NCT ID: NCT03877393

Last Updated: 2019-03-15

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-30
• Study Completion Date: 2021-02-28

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.

Conditions

Depressive Disorder, Major; Depression

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

PRO-GFD

Probiotic supplementation + gluten-free diet

Group Type: EXPERIMENTAL

Probiotic supplementation + gluten-free diet

Intervention Type: COMBINATION_PRODUCT

The probiotic and gluten-free diet group (PRO-GFD) will receive one capsule containing the probiotic mixture powder (Sanprobi Stress; Sanprobi sp. z o.o., sp.k., Szczecin, Poland) in the amount of 3 × 10\^9 colony forming units (CFU) per day divided in two equal doses, comprising two bacteria strains: Lactobacillus helveticusRosell®-52, Bifidobacterium longumRosell®-175, and excipients: potato starch, magnesium stearate, and the capsule shell of hydroxypropyl methylcellulose. The participants will be asked to consume supplements before breakfast. The group will follow the elimination diet containing no gluten.

PLA-GFD

Placebo supplementation + gluten-free diet

Group Type: PLACEBO_COMPARATOR

Placebo supplementation + gluten-free diet

Intervention Type: COMBINATION_PRODUCT

The placebo and gluten-free diet group (PLA-GFD) will receive one capsule containing only the excipients, i.e. maize starch, maltodextrins, and the capsule shell. The participants will be asked to consume supplements before breakfast. The group will follow the elimination diet containing no gluten.

PRO-GD

Probiotic supplementation + gluten-containing diet

Group Type: EXPERIMENTAL

Probiotic supplementation + gluten-containing diet

Intervention Type: COMBINATION_PRODUCT

The probiotic and gluten-containing diet group (PRO-GD) will receive one capsule containing the probiotic mixture powder (Sanprobi Stress; Sanprobi sp. z o.o., sp.k., Szczecin, Poland) in the amount of 3 × 10\^9 colony forming units (CFU) per day divided in two equal doses comprising two bacteria strains: Lactobacillus helveticusRosell®-52, Bifidobacterium longumRosell®-175 and excipients: potato starch, magnesium stearate, and the capsule shell of hydroxypropyl methylcellulose. The participants will be asked to consume supplements before breakfast. The group will stay with their current diet.

PLA-GD

Placebo supplementation + gluten-containing diet

Group Type: PLACEBO_COMPARATOR

Placebo supplementation + gluten-containing diet

Intervention Type: COMBINATION_PRODUCT

The placebo and gluten-containing diet group (PLA-GD) will receive one capsule containing only the excipients, i.e. maize starch, maltodextrins, and the capsule shell. The participants will be asked to consume supplements before breakfast. The group will stay with their current diet.

Interventions

Probiotic supplementation + gluten-free diet

The probiotic and gluten-free diet group (PRO-GFD) will receive one capsule containing the probiotic mixture powder (Sanprobi Stress; Sanprobi sp. z o.o., sp.k., Szczecin, Poland) in the amount of 3 × 10\^9 colony forming units (CFU) per day divided in two equal doses, comprising two bacteria strains: Lactobacillus helveticusRosell®-52, Bifidobacterium longumRosell®-175, and excipients: potato starch, magnesium stearate, and the capsule shell of hydroxypropyl methylcellulose. The participants will be asked to consume supplements before breakfast. The group will follow the elimination diet containing no gluten.

Intervention Type: COMBINATION_PRODUCT

Placebo supplementation + gluten-free diet

The placebo and gluten-free diet group (PLA-GFD) will receive one capsule containing only the excipients, i.e. maize starch, maltodextrins, and the capsule shell. The participants will be asked to consume supplements before breakfast. The group will follow the elimination diet containing no gluten.

Intervention Type: COMBINATION_PRODUCT

Probiotic supplementation + gluten-containing diet

The probiotic and gluten-containing diet group (PRO-GD) will receive one capsule containing the probiotic mixture powder (Sanprobi Stress; Sanprobi sp. z o.o., sp.k., Szczecin, Poland) in the amount of 3 × 10\^9 colony forming units (CFU) per day divided in two equal doses comprising two bacteria strains: Lactobacillus helveticusRosell®-52, Bifidobacterium longumRosell®-175 and excipients: potato starch, magnesium stearate, and the capsule shell of hydroxypropyl methylcellulose. The participants will be asked to consume supplements before breakfast. The group will stay with their current diet.

Intervention Type: COMBINATION_PRODUCT

Placebo supplementation + gluten-containing diet

The placebo and gluten-containing diet group (PLA-GD) will receive one capsule containing only the excipients, i.e. maize starch, maltodextrins, and the capsule shell. The participants will be asked to consume supplements before breakfast. The group will stay with their current diet.

Intervention Type: COMBINATION_PRODUCT

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanprobi Sp. z o.o., Sp. k., Szczecin, Poland

UNKNOWN

Sponsor Role: collaborator

Medical University of Lublin

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

1st Department of Psychiatry, Psychotherapy and Early Intervention, Medical University of Lublin

Lublin, , Poland

Site Status: RECRUITING

Countries

Poland

Central Contacts

Joanna Rog, MSc

Role: CONTACT

joannarog@umlub.pl

0048817487307

Malgorzata Futyma-Jedrzejewska, MD

Role: CONTACT

malgorzata.futyma-jedrzejewska@umlub.pl

0048817487307

Facility Contacts

Joanna Rog, MSc

Role: primary

joannarog@umlub.pl

0048817487307

Malgorzata Futyma-Jedrzejewska, MD

Role: backup

malgorzata.futyma-jedrzejewska@umlub.pl

0048817487307

References

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Reference Type: BACKGROUND

PMID: 29197739 (View on PubMed)

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Reference Type: BACKGROUND

PMID: 27509521 (View on PubMed)

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

PMID: 28806201 (View on PubMed)

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Reference Type: BACKGROUND

PMID: 30497694 (View on PubMed)

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Reference Type: BACKGROUND

PMID: 27884012 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 29710769 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 30544486 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31472678 (View on PubMed)

Other Identifiers

DS192/2019

Identifier Type: -

Identifier Source: org_study_id