Depressive Disorder, MajorSANGUTNCT03877393
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
A study testing Probiotic supplementation + gluten-free diet and Probiotic supplementation + gluten-containing diet in people with Depressive Disorder, Major and Depression, run by Medical University of Lublin at 1 site in Poland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Depressive Disorder, Major, Depression
- What is being tested?
- Probiotic supplementation + gluten-free diet and Probiotic supplementation + gluten-containing diet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 1 sitePoland
- Study dates
- Apr 2019to Feb 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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;
Show all 12Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
Poland1 site, 1 recruiting
- Recruiting
1st Department of Psychiatry, Psychotherapy and Early Intervention, Medical University of Lublin
Lublin, 20439
Joanna Rog, MSc, 0048817487307, joannarog@umlub.pl
Malgorzata Futyma-Jedrzejewska, MD, 0048817487307, malgorzata.futyma-jedrzejewska@umlub.pl
About this study
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
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
- Being tested
- Probiotic supplementation + gluten-free diet, Placebo supplementation + gluten-free diet, Probiotic supplementation + gluten-containing diet, Placebo supplementation + gluten-containing diet
- 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
- Medical subject headings
- Depressive Disorder, Major, Depression, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Probiotic supplementation + gluten-free dietCombination 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.
Placebo supplementation + gluten-free dietCombination 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.
Probiotic supplementation + gluten-containing dietCombination 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.
Placebo supplementation + gluten-containing dietCombination 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.
| Study group | Role | What they receive |
|---|---|---|
| PRO-GFD | Experimental | Probiotic supplementation + gluten-free diet Receives: Combination Product: Probiotic supplementation + gluten-free diet |
| PLA-GFD | Placebo comparator | Placebo supplementation + gluten-free diet Receives: Combination Product: Placebo supplementation + gluten-free diet |
| PRO-GD | Experimental | Probiotic supplementation + gluten-containing diet Receives: Combination Product: Probiotic supplementation + gluten-containing diet |
| PLA-GD | Placebo comparator | Placebo supplementation + gluten-containing diet Receives: Combination Product: Placebo supplementation + gluten-containing diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
The changes in Montgomery-Åsberg Depression Rating Scale(MADRS) total score to measure the severity of depression symptoms
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:
- 0 to 6: symptom absent
- 7 to 19: mild depression
- 20 to 34: moderate depression
- more than 34: severe depression
Measured: 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
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:
- 0 to 9: no/minimal depression
- 10 to 18: mild depression
- 19 to 29: moderate depression
- 30 to 63: severe depression
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: from the date of randomization until the end of the study up to 12 weeks
Secondary outcomes (24)
Changes in serum levels of high-specific C-reactive protein (hs-CRP)
Measured: from the date of randomization until the end of the study up to 12 weeks
Changes in serum levels of interleukin 6 (Il-6)
Measured: from the date of randomization until the end of the study up to 12 weeks
Changes in serum levels of interleukin 1beta (Il-1beta)
Measured: 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)
Measured: 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
Measured: 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
Measured: 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
Measured: 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)
Measured: from the date of randomization until the end of the study up to 12 weeks
Changes in serum levels of lipopolysaccharide biding protein (LBP)
Measured: from the date of randomization until the end of the study up to 12 weeks
Changes in serum levels of total cholesterol
Measured: 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
Measured: 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
Measured: from the date of randomization until the end of the study up to 12 weeks
Changes in serum levels of triglycerides (TG)
Measured: from the date of randomization until the end of the study up to 12 weeks
Changes in serum levels of glucose
Measured: from the date of randomization until the end of the study up to 12 weeks
Changes in serum levels of insulin
Measured: from the date of randomization until the end of the study up to 12 weeks
Changes in serum levels of cortisol
Measured: from the date of randomization until the end of the study up to 12 weeks
Changes in serum levels of alanine aminotransferase (ALT)
Measured: from the date of randomization until the end of the study up to 12 weeks
Changes in serum levels of aspartate aminotransferase (AST)
Measured: 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)
Measured: 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)
Measured: from the date of randomization until the end of the study up to 12 weeks
Changes in stool short-chain fatty acids (SCFAs) levels
Measured: 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)
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.
Measured: 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
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.
Measured: 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
Measured: from the date of randomization until the end of the study up to 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2019
- Study startApr 2019 (estimated)
- Primary completionJul 2020 (estimated)
- Study completionFeb 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Depressive Disorder, MajorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, double-blind, and placebo-controlled study
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medical University of Lublin
- Sponsor type
- University, hospital or other
- Collaborators
- Sanprobi Sp. z o.o., Sp. k., Szczecin, Poland
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03877393
- Sponsor's protocol ID
- DS192/2019
- Acronym
- SANGUT
- Status last verified
- Mar 2019
- First submitted
- 5 Mar 2019
- Last updated
- 15 Mar 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 29197739Huang 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.
PubMed 27509521Busby 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.
PubMed 30413036Dinan TG, Cryan JF. Brain-Gut-Microbiota Axis and Mental Health. Psychosom Med. 2017 Oct;79(8):920-926. doi: 10.1097/PSY.0000000000000519.
PubMed 28806201Dinan 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.
PubMed 30497694Slyepchenko 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.
PubMed 27884012Karakula-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.
PubMed 29710769Skonieczna-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.
PubMed 30544486Karakula-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.
PubMed 31472678
Study at a glance
From the registry record, last updated by the sponsor on 15 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03877393
- Acronym / sponsor ID
- SANGUT / DS192/2019
- 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
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Medical University of LublinUniversity, hospital or other
- Collaborators
- Sanprobi Sp. z o.o., Sp. k., Szczecin, Poland
- Study start
- Apr 2019 (estimated)
- Primary completion
- Jul 2020 (estimated)
- Study completion
- Feb 2021 (estimated)
- First posted
- 15 Mar 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- Randomized, double-blind, and placebo-controlled study
| Arm | Type | Receives |
|---|---|---|
| PRO-GFD | Experimental | Combination Product: Probiotic supplementation + gluten-free dietProbiotic supplementation + gluten-free diet |
| PLA-GFD | Placebo comparator | Combination Product: Placebo supplementation + gluten-free dietPlacebo supplementation + gluten-free diet |
| PRO-GD | Experimental | Combination Product: Probiotic supplementation + gluten-containing dietProbiotic supplementation + gluten-containing diet |
| PLA-GD | Placebo comparator | Combination Product: Placebo supplementation + gluten-containing dietPlacebo supplementation + gluten-containing diet |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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);
Key exclusion criteria (12 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Probiotic supplementation + gluten-free dietThe 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. | Combination product | PRO-GFD |
| Placebo supplementation + gluten-free dietThe 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. | Combination product | PLA-GFD |
| Probiotic supplementation + gluten-containing dietThe 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. | Combination product | PRO-GD |
| Placebo supplementation + gluten-containing dietThe 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. | Combination product | PLA-GD |
Primary outcome
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: * 0 to 6: symptom absent * 7 to 19: mild depression * 20 to 34: moderate depression * more than 34: severe depression
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: * 0 to 9: no/minimal depression * 10 to 18: mild depression * 19 to 29: moderate depression * 30 to 63: severe depression
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.
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.
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.
24 secondary outcomes
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
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
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
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
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
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
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
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
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
Changes in serum levels of total cholesterol
Time frame: 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
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
Changes in serum levels of triglycerides (TG)
Time frame: 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
Changes in serum levels of insulin
Time frame: 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
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
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
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
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
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
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
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
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 2019.
- Background: PubMed 29197739Ng 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.
- Background: PubMed 27509521Huang 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.
- Background: PubMed 30413036Busby 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.
- Background: PubMed 28806201Dinan TG, Cryan JF. Brain-Gut-Microbiota Axis and Mental Health. Psychosom Med. 2017 Oct;79(8):920-926. doi: 10.1097/PSY.0000000000000519.
- Background: PubMed 30497694Dinan 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.
- Background: PubMed 27884012Slyepchenko 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.
- Background: PubMed 29710769Karakula-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.
- Background: PubMed 30544486Skonieczna-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.
- Derived from this study: PubMed 31472678Karakula-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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Probiotic supplementation + gluten-free diet and Probiotic supplementation + gluten-containing diet in people with Depressive Disorder, Major and Depression, run by Medical University of Lublin at 1 site in Poland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 15 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Poland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Joanna Rog, MSc (0048817487307, joannarog@umlub.pl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03877393, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Mar 2019.