Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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Recruitment Status
TERMINATED
Total Enrollment
51 participants
Study Classification
OBSERVATIONAL
Study Start Date
2022-01-27
Study Completion Date
2024-10-29
Brief Summary
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The purpose of this project is to determine if specific gut microbiome or gut-derived metabolites are associated with depression in patients with Multiple Sclerosis (pwMS). Mechanistically, the investigators further hypothesize that depression in pwMS is related to decreased abundance of gut bacteria with GABA-producing activities and/or with anti-inflammatory properties. To determine if the presence of depression in pwMS is associated with specific gut microbiome, gut-derived metabolites or peripheral blood immune profiles. The investigators will perform a cross-sectional study in clinically stable pwMS recruited at the John L. Trotter MS Center. The investigators will evaluate the presence of depression using the Quality of Life in Neurological Disorders (Neuro-Qol) depression scale, one of the 13 scales in the Neuro-Qol recently developed by the NIH using modern psychometric techniques and validated in pwMS.
A total of 120 pwMS will be recruited: 60 with and 60 without depression based on the Neuro-Qol depression scale. At the study visit each participant will be asked to provide a stool sample for microbiome analyses and a blood sample for peripheral blood immunophenotyping. Potential confounders will be collected and treated as covariates in the analyses. These include: 1) degree of disability (EDSS); 2) treatment with anti-depressants and DMTs; 3) a 4-days food diary to evaluate diet composition; 4) weight and height to calculate the BMI; 5) fatigue; 6) level of physical activity; 7) sleep quality.
A total of 120 pwMS will be recruited: 60 with and 60 without depression based on the Neuro-Qol depression scale. At the study visit each participant will be asked to provide a stool sample for microbiome analyses and a blood sample for peripheral blood immunophenotyping. Potential confounders will be collected and treated as covariates in the analyses. These include: 1) degree of disability (EDSS); 2) treatment with anti-depressants and DMTs; 3) a 4-days food diary to evaluate diet composition; 4) weight and height to calculate the BMI; 5) fatigue; 6) level of physical activity; 7) sleep quality.
Detailed Description
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Our overall hypothesis is that specific gut microbiome or gut-derived metabolites are associated with depression in pwMS. Mechanistically, the investigators further hypothesize that depression in pwMS is related to decreased abundance of gut bacteria with GABA-producing activities and/or with anti-inflammatory properties.
AIM 1. To determine if the presence of depression in pwMS is associated with specific gut microbiome, gut-derived metabolites or peripheral blood immune profiles.
The investigators will perform a cross-sectional study in clinically stable pwMS recruited at the John L. Trotter MS Center. The investigators will evaluate the presence of depression using the Quality of Life in Neurological Disorders (Neuro-Qol) depression scale, one of the 13 scales in the Neuro-Qol recently developed by the NIH using modern psychometric techniques and validated in pwMS. A total of 120 pwMS will be recruited: 60 with and 60 without depression based on the Neuro-Qol depression scale. At the study visit each participant will be asked to provide a stool sample for microbiome analyses and a blood sample for peripheral blood immunophenotyping. Potential confounders will be collected and treated as covariates in the analyses. These include: 1) degree of disability (EDSS); 2) treatment with anti-depressants and DMTs; 3) a 4-days food diary to evaluate diet composition; 4) the investigatorsight and height to calculate the BMI; 5) fatigue; 6) level of physical activity; 7) sleep quality.
AIM 1A. To determine if depression will correlate with specific gut microbiome or gut-derived metabolites profiles in pwMS.
Stool samples will be processed for microbiome sequencing and metabolome characterization.
AIM 1B. To determine if depression will correlate with a specific peripheral blood immune-inflammatory profile in pwMS.
A peripheral blood sample will be obtained from each participant to perform: 1) peripheral blood immune cell phenotyping to characterize the main immune cell subsets and their activation; 2) intracellular cytokine production to study cytokine production profiles of blood lymphocytes and monocytes.
AIM 2. To quantify GABA production in pwMS with or without depression and determine gut microbiome-immune system interaction in vitro.
In this aim the investigators will perform functional studies to evaluate the potential of gut microbiota from pwMS with or without depression to produce GABA and to modulate immune-inflammatory responses.
AIM 2A. To quantify GABA levels in whole stool, specific stool bacterial isolates and blood of pwMS with or without depression.
The investigators will evaluate GABA levels in the stool and blood of pwMS. In addition, the investigators will measure GABA production by Bacteroides ssp isolated from the gut microbiota of pwMS.
Aim 2B. To evaluate the effects of whole stool and specific bacterial species from pwMS on blood immune cell phenotype and cytokine production.
The investigators will test how whole gut microbiome or specific bacteria (identified in Aim 1 as associated with depression in pwMS) can modulate immune cell function. Peripheral blood mononuclear cells (PBMC) from healthy donors will be cultured in conditioning media from whole stool or bacteria of interest isolated from pwMS. PBMC phenotype and cytokine production after exposure in vitro will be characterized by flow cytometry.
AIM 1. To determine if the presence of depression in pwMS is associated with specific gut microbiome, gut-derived metabolites or peripheral blood immune profiles.
The investigators will perform a cross-sectional study in clinically stable pwMS recruited at the John L. Trotter MS Center. The investigators will evaluate the presence of depression using the Quality of Life in Neurological Disorders (Neuro-Qol) depression scale, one of the 13 scales in the Neuro-Qol recently developed by the NIH using modern psychometric techniques and validated in pwMS. A total of 120 pwMS will be recruited: 60 with and 60 without depression based on the Neuro-Qol depression scale. At the study visit each participant will be asked to provide a stool sample for microbiome analyses and a blood sample for peripheral blood immunophenotyping. Potential confounders will be collected and treated as covariates in the analyses. These include: 1) degree of disability (EDSS); 2) treatment with anti-depressants and DMTs; 3) a 4-days food diary to evaluate diet composition; 4) the investigatorsight and height to calculate the BMI; 5) fatigue; 6) level of physical activity; 7) sleep quality.
AIM 1A. To determine if depression will correlate with specific gut microbiome or gut-derived metabolites profiles in pwMS.
Stool samples will be processed for microbiome sequencing and metabolome characterization.
AIM 1B. To determine if depression will correlate with a specific peripheral blood immune-inflammatory profile in pwMS.
A peripheral blood sample will be obtained from each participant to perform: 1) peripheral blood immune cell phenotyping to characterize the main immune cell subsets and their activation; 2) intracellular cytokine production to study cytokine production profiles of blood lymphocytes and monocytes.
AIM 2. To quantify GABA production in pwMS with or without depression and determine gut microbiome-immune system interaction in vitro.
In this aim the investigators will perform functional studies to evaluate the potential of gut microbiota from pwMS with or without depression to produce GABA and to modulate immune-inflammatory responses.
AIM 2A. To quantify GABA levels in whole stool, specific stool bacterial isolates and blood of pwMS with or without depression.
The investigators will evaluate GABA levels in the stool and blood of pwMS. In addition, the investigators will measure GABA production by Bacteroides ssp isolated from the gut microbiota of pwMS.
Aim 2B. To evaluate the effects of whole stool and specific bacterial species from pwMS on blood immune cell phenotype and cytokine production.
The investigators will test how whole gut microbiome or specific bacteria (identified in Aim 1 as associated with depression in pwMS) can modulate immune cell function. Peripheral blood mononuclear cells (PBMC) from healthy donors will be cultured in conditioning media from whole stool or bacteria of interest isolated from pwMS. PBMC phenotype and cytokine production after exposure in vitro will be characterized by flow cytometry.
Conditions
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Multiple Sclerosis
Depression
Keywords
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Multiple Sclerosis
Depression
Microbiome
Study Design
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Observational Model Type
COHORT
Study Time Perspective
CROSS_SECTIONAL
Study Groups
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With Neuro-QoL Depression scale T-score > 55
1. Collection of demographic and clinical data (age, gender, BMI, ethnicity, age of onset, number of relapses).
2. Administration of the Neuro-QoL depression scale
3. Neurological exam to evaluate disability and calculate the EDSS score (ranging from 0 to 10)
4. Neurological cognitive and functional assessments: a 9-hole Peg Test and 25-ft Timed Walk from the Multiple Sclerosis Functional Composite (MSFC); the Symbol Digit Modality Test (SDMT)
5. Administration of the Fatigue Severity Scale (FSS)
6. Collection of a 4-days food diary to evaluate diet composition of enrolled pwMS
7. Administration of the Stanford 7-day Physical Activity Recall Scale (PAR)
8. Evaluation of sleep quality by administration of the Neuro-QoL sleep disturbance scale
9. Collection of a stool sample for gut microbiome and metabolome analyses
10. Collection of a saliva sample for microbiome and metabolome analyses
Neuro-QoL T-score determination
Intervention Type
OTHER
Neuro-Qol depression scale, using a T-score of 55 as a threshold
With Neuro-QoL Depression scale T-score < 55
1. Collection of demographic and clinical data (age, gender, BMI, ethnicity, age of onset, number of relapses).
2. Administration of the Neuro-QoL depression scale
3. Neurological exam to evaluate disability and calculate the EDSS score (ranging from 0 to 10)
4. Neurological cognitive and functional assessments: a 9-hole Peg Test and 25-ft Timed Walk from the Multiple Sclerosis Functional Composite (MSFC); the Symbol Digit Modality Test (SDMT)
5. Administration of the Fatigue Severity Scale (FSS)
6. Collection of a 4-days food diary to evaluate diet composition of enrolled pwMS
7. Administration of the Stanford 7-day Physical Activity Recall Scale (PAR)
8. Evaluation of sleep quality by administration of the Neuro-QoL sleep disturbance scale
9. Collection of a stool sample for gut microbiome and metabolome analyses
10. Collection of a saliva sample for microbiome and metabolome analyses
Neuro-QoL T-score determination
Intervention Type
OTHER
Neuro-Qol depression scale, using a T-score of 55 as a threshold
Interventions
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Neuro-QoL T-score determination
Neuro-Qol depression scale, using a T-score of 55 as a threshold
Intervention Type
OTHER
Eligibility Criteria
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Inclusion Criteria
1. Age ≥18 years
2. Diagnosis of RRMS or progressive MS based on the 2017 revised McDonald criteria
3. Untreated or on any of the MS DMTs as long as they have been stable clinically in the previous 3 months
4. No history of antibiotic treatment in the 3 months prior to study visit and sample collection
5. No other autoimmune diseases, chronic metabolic diseases (e.g. diabetes) or conditions (e.g. pregnancy) that would interfere with the parameters that we will be measuring in the stool and blood samples.
2. Diagnosis of RRMS or progressive MS based on the 2017 revised McDonald criteria
3. Untreated or on any of the MS DMTs as long as they have been stable clinically in the previous 3 months
4. No history of antibiotic treatment in the 3 months prior to study visit and sample collection
5. No other autoimmune diseases, chronic metabolic diseases (e.g. diabetes) or conditions (e.g. pregnancy) that would interfere with the parameters that we will be measuring in the stool and blood samples.
Minimum Eligible Age
18 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
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University of Connecticut
OTHER
Sponsor Role
collaborator
University of Texas
OTHER
Sponsor Role
collaborator
Washington University School of Medicine
OTHER
Sponsor Role
lead
Responsible Party
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Responsibility Role
SPONSOR
Principal Investigators
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Laura Piccio, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
Washington University School of Medicine
Locations
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Washington University in St Louis
St Louis, Missouri, United States
Site Status
Countries
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United States
References
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Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
202107067
Identifier Type: -
Identifier Source: org_study_id