- ICH GCP
- US Clinical Trials Registry
- 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 (SANGUT)
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 Overview
Status
Conditions
Study Type
Enrollment (Anticipated)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
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Lublin, Poland, 20439
- Recruiting
- 1st Department of Psychiatry, Psychotherapy and Early Intervention, Medical University of Lublin
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Contact:
- Joanna Rog, MSc
- Phone Number: 0048817487307
- Email: joannarog@umlub.pl
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Contact:
- Malgorzata Futyma-Jedrzejewska, MD
- Phone Number: 0048817487307
- Email: malgorzata.futyma-jedrzejewska@umlub.pl
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Principal Investigator:
- Hanna Karakula-Juchnowicz, Prof, PhD, MD
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Principal Investigator:
- Joanna Rog, MSc
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Sub-Investigator:
- Dariusz Juchnowicz, PhD, MD
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Sub-Investigator:
- Malgorzata Futyma-Jedrzejewska, MD
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Outpatients aged 18-60 years old;
- Signed written Informed Consent Form;
- Meet the DSM-5 criteria for MDD;
- Body mass index (BMI) ≥18.5 kg/m2 and ≤30 kg/m2;
- MADRS (Montgomery-Asberg Depression Scale) total score at screening (V0) and at baseline (V1) of 20 points or more (moderate or severe depression);
- A willingness and motivation to follow the study protocol.
Exclusion Criteria:
- Diagnosis of autoimmune, neurological, immunocompromised, thyroid, inflammatory bowel diseases, diabetes, cancers, and/or IgE-dependent allergy;
- Psychiatric comorbidities (except specific personality disorder) including mental retardation, organic brain dysfunction, or addiction (except nicotine and caffeine);
- High risk of suicide in the investigator's opinion;
- An infection one month before the study baseline visit (V1);
- The use of antibiotics and/or probiotics three months prior to the study;
- Glucocorticosteroids and/or metformin treatment;
- Intake of any other drugs which in the investigator' opinion may affect the results of study;
- 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;
- Changes in a pharmacotherapy and/or psychotherapy of MDD 2 weeks before the trial entry;
- Electroconvulsive therapy (ECT) 12 months before the trial entry;
- No specific diet (e.g., elimination, vegan, reduction) and changes in physical activity 4 weeks before the trial entry;
- Pregnancy or lactation.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: PRO-GFD
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.
|
Placebo Comparator: PLA-GFD
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.
|
Experimental: PRO-GD
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.
|
Placebo Comparator: PLA-GD
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The changes in Montgomery-Åsberg Depression Rating Scale(MADRS) total score to measure the severity of depression symptoms
Time Frame: from the date of randomization until the end of the study up to 12 weeks
|
A 10-item questionnaire to measure the severity of depressive symptoms in individuals with mood disorders. The assessment is performed by an experienced clinical psychiatrist. Each item yields a score of 0 to 6 (overall score ranges from 0 to 60). The higher score indicates a higher severity of the depressive episode. MADRS cut-off points include:
|
from the date of randomization until the end of the study up to 12 weeks
|
The changes in Beck Depression Inventory (BDI) total score to measure the severity of depression symptoms
Time Frame: from the date of randomization until the end of the study up to 12 weeks
|
A 21-item multiple-choice self-report inventory to measure the severity of depression. Each item yields a score of 0 to 3 (overall score ranges from 0 to 63). The higher score indicates more severe depression symptoms. BDI cut-off points include:
|
from the date of randomization until the end of the study up to 12 weeks
|
The changes in Symptom Checklist-90 (SCL-90) total score to measure the severity of psychopathological impairment
Time Frame: from the date of randomization until the end of the study up to 12 weeks
|
A 90-item self-reported inventory to evaluate a broad range of psychological problems and symptoms of psychopathology.
The SCL-90 measure symptom intensity on nine different subscales: somatization, obsessive-compulsive, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation, psychoticism.
Each item yields a score of 0 to 4 (overall score ranges from 0 to 364).
The higher score indicates more severity of symptoms.
|
from the date of randomization until the end of the study up to 12 weeks
|
The changes in the 36-Item Short Form Survey (SF-36) total score to measure the quality of life
Time Frame: from the date of randomization until the end of the study up to 12 weeks
|
A 36-item self-reported survey to evaluate a health status including vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health.
Raw scores are transforming to 0-100 scale.
The higher score indicates a better health state.
|
from the date of randomization until the end of the study up to 12 weeks
|
The changes in the Perceived Stress Scale (PSS-10) total score to measure the stress levels
Time Frame: from the date of randomization until the end of the study up to 12 weeks
|
A 10-item self-reported questionnaire to measure the perception of stress.
Each item yields a score of 0 to 4 (overall score ranges from 0 to 40).
The higher score indicates higher perceived stress.
|
from the date of randomization until the end of the study up to 12 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes in serum levels of high-specific C-reactive protein (hs-CRP)
Time Frame: from the date of randomization until the end of the study up to 12 weeks
|
from the date of randomization until the end of the study up to 12 weeks
|
|
Changes in serum levels of interleukin 6 (Il-6)
Time Frame: from the date of randomization until the end of the study up to 12 weeks
|
from the date of randomization until the end of the study up to 12 weeks
|
|
Changes in serum levels of interleukin 1beta (Il-1beta)
Time Frame: from the date of randomization until the end of the study up to 12 weeks
|
from the date of randomization until the end of the study up to 12 weeks
|
|
Changes in serum levels of tumor necrosis factor alpha (TNF-alpha)
Time Frame: from the date of randomization until the end of the study up to 12 weeks
|
from the date of randomization until the end of the study up to 12 weeks
|
|
Changes in serum levels of anti-tissue transglutaminase (anti-TG2) IgG antibodies
Time Frame: from the date of randomization until the end of the study up to 12 weeks
|
from the date of randomization until the end of the study up to 12 weeks
|
|
Changes in serum levels of anti-gliadin (anti-AGA) IgG antibodies
Time Frame: from the date of randomization until the end of the study up to 12 weeks
|
from the date of randomization until the end of the study up to 12 weeks
|
|
Changes in serum levels of anti-gliadin (anti-AGA) IgA antibodies
Time Frame: from the date of randomization until the end of the study up to 12 weeks
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from the date of randomization until the end of the study up to 12 weeks
|
|
Changes in serum levels of intestinal fatty acid-binding protein (I-FABP/FABP-2)
Time Frame: from the date of randomization until the end of the study up to 12 weeks
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from the date of randomization until the end of the study up to 12 weeks
|
|
Changes in serum levels of lipopolysaccharide biding protein (LBP)
Time Frame: from the date of randomization until the end of the study up to 12 weeks
|
from the date of randomization until the end of the study up to 12 weeks
|
|
Changes in serum levels of total cholesterol
Time Frame: from the date of randomization until the end of the study up to 12 weeks
|
from the date of randomization until the end of the study up to 12 weeks
|
|
Changes in serum levels of low-density lipoprotein (LDL) cholesterol
Time Frame: from the date of randomization until the end of the study up to 12 weeks
|
from the date of randomization until the end of the study up to 12 weeks
|
|
Changes in serum levels of high-density lipoprotein (HDL) cholesterol
Time Frame: from the date of randomization until the end of the study up to 12 weeks
|
from the date of randomization until the end of the study up to 12 weeks
|
|
Changes in serum levels of triglycerides (TG)
Time Frame: from the date of randomization until the end of the study up to 12 weeks
|
from the date of randomization until the end of the study up to 12 weeks
|
|
Changes in serum levels of glucose
Time Frame: from the date of randomization until the end of the study up to 12 weeks
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from the date of randomization until the end of the study up to 12 weeks
|
|
Changes in serum levels of insulin
Time Frame: from the date of randomization until the end of the study up to 12 weeks
|
from the date of randomization until the end of the study up to 12 weeks
|
|
Changes in serum levels of cortisol
Time Frame: from the date of randomization until the end of the study up to 12 weeks
|
from the date of randomization until the end of the study up to 12 weeks
|
|
Changes in serum levels of alanine aminotransferase (ALT)
Time Frame: from the date of randomization until the end of the study up to 12 weeks
|
from the date of randomization until the end of the study up to 12 weeks
|
|
Changes in serum levels of aspartate aminotransferase (AST)
Time Frame: from the date of randomization until the end of the study up to 12 weeks
|
from the date of randomization until the end of the study up to 12 weeks
|
|
Changes in diversity in microbial community in a single sample (alpha-diversity)
Time Frame: from the date of randomization until the end of the study up to 12 weeks
|
from the date of randomization until the end of the study up to 12 weeks
|
|
Changes in diversity in microbial community between samples (beta-diversity)
Time Frame: from the date of randomization until the end of the study up to 12 weeks
|
from the date of randomization until the end of the study up to 12 weeks
|
|
Changes in stool short-chain fatty acids (SCFAs) levels
Time Frame: from the date of randomization until the end of the study up to 12 weeks
|
from the date of randomization until the end of the study up to 12 weeks
|
|
Changes in electroencephalography (EEG) analysis to assess the functional connectivity (FC)
Time Frame: from the date of randomization until the end of the study up to 12 weeks
|
FC will be assessed, based on resting-state EEG-recordings, with the application of a Phase Lag Index (PLI), measuring connectivity strength between a given pair of cortical areas.
The global neural network organization will be analyzed with Minimum Spanning Tree algorithm.
|
from the date of randomization until the end of the study up to 12 weeks
|
Changes in Gastrointestinal Symptom Rating Scale (GSRS) total score to measure intensity of experienced gastrointestinal symptoms
Time Frame: from the date of randomization until the end of the study up to 12 weeks
|
A 15-item self-reported questionnaire to measure gastrointestinal symptoms in five clusters: reflux, abdominal pain, indigestion, diarrhoea and constipation.
Each item yields a score of 0 to 3 (overall score ranges from 0 to 45).
The higher score indicates a higher intensity of experienced symptoms.
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from the date of randomization until the end of the study up to 12 weeks
|
Changes in Trail Making Test (TMT) to measure the cognitive abilities
Time Frame: from the date of randomization until the end of the study up to 12 weeks
|
from the date of randomization until the end of the study up to 12 weeks
|
Collaborators and Investigators
Sponsor
Collaborators
Publications and helpful links
General Publications
- Ng QX, Peters C, Ho CYX, Lim DY, Yeo WS. A meta-analysis of the use of probiotics to alleviate depressive symptoms. J Affect Disord. 2018 Mar 1;228:13-19. doi: 10.1016/j.jad.2017.11.063. Epub 2017 Nov 16.
- Huang R, Wang K, Hu J. Effect of Probiotics on Depression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrients. 2016 Aug 6;8(8):483. doi: 10.3390/nu8080483.
- Busby E, Bold J, Fellows L, Rostami K. Mood Disorders and Gluten: It's Not All in Your Mind! A Systematic Review with Meta-Analysis. Nutrients. 2018 Nov 8;10(11):1708. doi: 10.3390/nu10111708.
- Dinan TG, Cryan JF. Brain-Gut-Microbiota Axis and Mental Health. Psychosom Med. 2017 Oct;79(8):920-926. doi: 10.1097/PSY.0000000000000519.
- Dinan TG, Stanton C, Long-Smith C, Kennedy P, Cryan JF, Cowan CSM, Cenit MC, van der Kamp JW, Sanz Y. Feeding melancholic microbes: MyNewGut recommendations on diet and mood. Clin Nutr. 2019 Oct;38(5):1995-2001. doi: 10.1016/j.clnu.2018.11.010. Epub 2018 Nov 17.
- Slyepchenko A, Maes M, Jacka FN, Kohler CA, Barichello T, McIntyre RS, Berk M, Grande I, Foster JA, Vieta E, Carvalho AF. Gut Microbiota, Bacterial Translocation, and Interactions with Diet: Pathophysiological Links between Major Depressive Disorder and Non-Communicable Medical Comorbidities. Psychother Psychosom. 2017;86(1):31-46. doi: 10.1159/000448957. Epub 2016 Nov 25.
- 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.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- DS192/2019
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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