Systemic SclerosisPhase 3SScNCT02302352
Effects of Probiotics on Gastrointestinal Symptoms and on the Immune System in Patients With Systemic Sclerosis
A Phase 3 study testing Probiotic in people with Systemic Sclerosis and Scleroderma, run by Federal University of São Paulo at 1 site in Brazil.
Trial summary
Systemic sclerosis (SSc) is an autoimmune disease with unknown etiology, which affects especially the gastrointestinal tract, lungs, heart and kidneys. Immunological abnormalities characterized by innate and acquired immune disturbances are associated with the disease development. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Systemic Sclerosis, Scleroderma
- What is being tested?
- Probiotic
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 76 participants
- Where
- 1 siteBrazil
- Study dates
- Dec 2014to Jan 2016
- Phase
- Phase 3
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Patients with systemic sclerosis according to the 2013 ACR/EULAR classification criteria for SSc;
- Patients with gastrointestinal symptoms related to SSc including: gastrointestinal reflux, bloating, diarrhea and constipation;
- Written informed consent provided by the subjects.
Who cannot join
- Overlap syndromes with systemic lupus erythematosus, polymyositis/dermatomyositis and rheumatoid arthritis;
- Use of antibiotics and/or probiotics four weeks before baseline;
Trial locations and contacts
1 site in 1 country.
Brazil1 site
Systemic Sclerosis Outpatient Clinic, Hospital São Paulo
São Paulo, São Paulo
About this study
Official title: Effects of Probiotics on Gastrointestinal Symptoms and on the Immune System in Patients With Systemic Sclerosis: a Randomized Double-blind Placebo-controlled Clinical Trial
Systemic sclerosis (SSc) is an autoimmune disease with unknown etiology, which affects especially the gastrointestinal tract, lungs, heart and kidneys. Immunological abnormalities characterized by innate and acquired immune disturbances are associated with the disease development. The present study aims to evaluate the efficacy and safety of probiotics in gastrointestinal symptoms, nutritional status and innate and acquired immune responses, by means of the evaluation of IgA, Treg and Th1, Th2, and Th17 T helper subtypes levels in patients with SSc. In addition the levels of CD4+ T helper Th1, Th2 and Th17 subtypes and Treg levels will be compared to a healthy control group.
Read the detailed description
Systemic sclerosis (SSc) is a chronic autoimmune disease, which affects the gastrointestinal tract, lungs, heart and kidneys. A shift in the balance between T helper 1 (Th1) and Th2 subtypes and between regulatory T cells (Treg) and Th17 cells levels, as well as intestinal microbiota abnormalities may be present in SSc. These abnormalities can stimulate inflammatory response, and cause intestinal epithelial damage. The use of oral probiotics for microbiome or immune response modulation can be attractive especially in autoimmune diseases. Objectives: To evaluate the efficacy and safety of probiotics in gastrointestinal symptoms, nutritional status and innate and acquired immune responses, by means of the evaluation of IgA, Treg and Th1, Th2, and Th17 T helper subtypes levels in patients with SSc. In addition the levels of CD4+ T helper Th1, Th2 and Th17 subtypes and Treg levels will be compared to a healthy control group. Patients and methods: A randomized double-blind placebo-controlled clinical trial, with 76 SSc patients will be performed. Patients will be randomly assigned to receive oral probiotics once a day or placebo for 8 weeks. The primary outcome will be changes in the gastrointestinal symptoms between baseline and week 8. Clinical evaluation, scleroderma Health Assessment Questionnaire (sHAQ), food intake record, anthropometry assessment and laboratory evaluation will be performed at baseline (T0), at week 4 (T1) and week 8 (T2). C-reactive protein (CRP) and immunoglobulin A (IgA) serum levels assessment will be performed at each visit. The proportion of CD4+ and CD8+ T cells, and Tregs (CD4+CD25+Foxp3+CD127low), and Th1, Th2 e Th17 CD4+ T cell subsets levels will be evaluated using flow cytometer at each visit in SSc patients and also in 50 healthy subjetcs.
- Conditions
- Systemic Sclerosis, Scleroderma
- Being tested
- Probiotic, Placebo
- Keywords
- Probiotics, Immune system
- Medical subject headings
- Scleroderma, Systemic, Scleroderma, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ProbioticOther
Also called Lacto Pro
Probiotic 1g once a day by mouth for 8 weeks
PlaceboOther
Maltodextrin 1g, manufactured to mimic the probiotic, once a day by mounth for 8 weeks
| Study group | Role | What they receive |
|---|---|---|
| Probiotic | Active comparator | Oral probiotic 1g, once/day, containing: Lactobacillus paracasei, 10x9 CFU; Lactobacillus rhamnosus,10x9 CFU; Lactobacillus acidophillus, 10x9 CFU; Bifidobacterium lactis 10x9 CFU per sachet Receives: Other: Probiotic |
| Placebo | Placebo comparator | Maltodextrin 1g per sachet, once/day Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in the gastrointestinal symptoms as measured by the "The University of California Los Angeles Scleroderma Clinical Trials Consortium Gastrointestinal Tract 2.0 (GIT 2.0)" Questionnaire
Measured: baseline and eight weeks
Secondary outcomes (7)
Scleroderma Health Assessment Questionnaire (sHAQ)
Measured: baseline and eight weeks
Food intake record
Measured: baseline and eight weeks
Anthropometry assessment as measured by the body mass index (BMI)
Measured: baseline and eight weeks
C-reactive protein (CRP) and immunoglobulin A (IgA) serum levels
Measured: baseline and eight weeks
Proportion of CD4+ and CD8+ T cells
Measured: baseline and eight weeks
Tregs (CD4+CD25+Foxp3+CD127low) levels
Measured: baseline and eight weeks
Th1, Th2 and Th17 CD4+ T cell subsets levels
Measured: baseline and eight weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Nov 2014 (estimated)
- Study startDec 2014
- Primary completionApr 2015 (estimated)
- Study completionJan 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Systemic SclerosisStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 76 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Federal University of São Paulo
- Sponsor type
- University, hospital or other
- Collaborators
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Responsible party
- Principal investigator, Cristiane Kayser, Federal University of São Paulo
- Investigators
- Cristiane Kayser, Principal investigator, Associate Professor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02302352
- Sponsor's protocol ID
- 2013/26788-3
- Acronym
- SSc
- Status last verified
- Nov 2014
- First submitted
- 17 Nov 2014
- Last updated
- 27 Nov 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Marighela TF, Arismendi MI, Marvulle V, Brunialti MKC, Salomao R, Kayser C. Effect of probiotics on gastrointestinal symptoms and immune parameters in systemic sclerosis: a randomized placebo-controlled trial. Rheumatology (Oxford). 2019 Nov 1;58(11):1985-1990. doi: 10.1093/rheumatology/kez160.
PubMed 31056685
Study at a glance
From the registry record, last updated by the sponsor on 27 Nov 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Probiotics on Gastrointestinal Symptoms and on the Immune System in Patients With Systemic Sclerosis: a Randomized Double-blind Placebo-controlled Clinical Trial
- ClinicalTrials.gov ID
- NCT02302352
- Acronym / sponsor ID
- SSc / 2013/26788-3
- Conditions
- Systemic Sclerosis, Scleroderma
- Keywords
- Probiotics, Immune system
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 76 participants (estimated)
- Lead sponsor
- Federal University of São PauloUniversity, hospital or other
- Collaborators
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Study start
- Dec 2014
- Primary completion
- Apr 2015 (estimated)
- Study completion
- Jan 2016 (estimated)
- First posted
- 27 Nov 2014 (estimated)
- 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.
Systemic sclerosis (SSc) is an autoimmune disease with unknown etiology, which affects especially the gastrointestinal tract, lungs, heart and kidneys. Immunological abnormalities characterized by innate and acquired immune disturbances are associated with the disease development. The present study aims to evaluate the efficacy and safety of probiotics in gastrointestinal symptoms, nutritional status and innate and acquired immune responses, by means of the evaluation of IgA, Treg and Th1, Th2, and Th17 T helper subtypes levels in patients with SSc. In addition the levels of CD4+ T helper Th1, Th2 and Th17 subtypes and Treg levels will be compared to a healthy control group.
Detailed description
Systemic sclerosis (SSc) is a chronic autoimmune disease, which affects the gastrointestinal tract, lungs, heart and kidneys. A shift in the balance between T helper 1 (Th1) and Th2 subtypes and between regulatory T cells (Treg) and Th17 cells levels, as well as intestinal microbiota abnormalities may be present in SSc. These abnormalities can stimulate inflammatory response, and cause intestinal epithelial damage. The use of oral probiotics for microbiome or immune response modulation can be attractive especially in autoimmune diseases. Objectives: To evaluate the efficacy and safety of probiotics in gastrointestinal symptoms, nutritional status and innate and acquired immune responses, by means of the evaluation of IgA, Treg and Th1, Th2, and Th17 T helper subtypes levels in patients with SSc. In addition the levels of CD4+ T helper Th1, Th2 and Th17 subtypes and Treg levels will be compared to a healthy control group. Patients and methods: A randomized double-blind placebo-controlled clinical trial, with 76 SSc patients will be performed. Patients will be randomly assigned to receive oral probiotics once a day or placebo for 8 weeks. The primary outcome will be changes in the gastrointestinal symptoms between baseline and week 8. Clinical evaluation, scleroderma Health Assessment Questionnaire (sHAQ), food intake record, anthropometry assessment and laboratory evaluation will be performed at baseline (T0), at week 4 (T1) and week 8 (T2). C-reactive protein (CRP) and immunoglobulin A (IgA) serum levels assessment will be performed at each visit. The proportion of CD4+ and CD8+ T cells, and Tregs (CD4+CD25+Foxp3+CD127low), and Th1, Th2 e Th17 CD4+ T cell subsets levels will be evaluated using flow cytometer at each visit in SSc patients and also in 50 healthy subjetcs.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Probiotic | Active comparator | Other: ProbioticOral probiotic 1g, once/day, containing: Lactobacillus paracasei, 10x9 CFU; Lactobacillus rhamnosus,10x9 CFU; Lactobacillus acidophillus, 10x9 CFU; Bifidobacterium lactis 10x9 CFU per sachet |
| Placebo | Placebo comparator | Other: PlaceboMaltodextrin 1g per sachet, once/day |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Patients with systemic sclerosis according to the 2013 ACR/EULAR classification criteria for SSc;
- Patients with gastrointestinal symptoms related to SSc including: gastrointestinal reflux, bloating, diarrhea and constipation;
- Written informed consent provided by the subjects.
Key exclusion criteria (2 listed)
- Overlap syndromes with systemic lupus erythematosus, polymyositis/dermatomyositis and rheumatoid arthritis;
- Use of antibiotics and/or probiotics four weeks before baseline;
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 |
|---|---|---|
| ProbioticAlso: Lacto ProProbiotic 1g once a day by mouth for 8 weeks | Other | Probiotic |
| PlaceboMaltodextrin 1g, manufactured to mimic the probiotic, once a day by mounth for 8 weeks | Other | Placebo |
Primary outcome
Changes in the gastrointestinal symptoms as measured by the "The University of California Los Angeles Scleroderma Clinical Trials Consortium Gastrointestinal Tract 2.0 (GIT 2.0)" Questionnaire
Time frame: baseline and eight weeks
7 secondary outcomes
Scleroderma Health Assessment Questionnaire (sHAQ)
Time frame: baseline and eight weeks
Food intake record
Time frame: baseline and eight weeks
Anthropometry assessment as measured by the body mass index (BMI)
Time frame: baseline and eight weeks
C-reactive protein (CRP) and immunoglobulin A (IgA) serum levels
Time frame: baseline and eight weeks
Proportion of CD4+ and CD8+ T cells
Time frame: baseline and eight weeks
Tregs (CD4+CD25+Foxp3+CD127low) levels
Time frame: baseline and eight weeks
Th1, Th2 and Th17 CD4+ T cell subsets levels
Time frame: baseline and eight weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Nov 2014.
- Derived from this study: PubMed 31056685Marighela TF, Arismendi MI, Marvulle V, Brunialti MKC, Salomao R, Kayser C. Effect of probiotics on gastrointestinal symptoms and immune parameters in systemic sclerosis: a randomized placebo-controlled trial. Rheumatology (Oxford). 2019 Nov 1;58(11):1985-1990. doi: 10.1093/rheumatology/kez160.
Related trials for Systemic Sclerosis
Not yet recruitingPhase 2
Hyaluronidase Injections for Sclerodactyly in Patients With Scleroderma
Scleroderma, Sclerodactyly
RecruitingPhase 1
A Trial in Healthy Adult Participants and Adults With Autoimmune Diseases to Test How HBM7020 is Tolerated and How it Behaves in the Body
Rheumatoid Arthritis, Systemic Lupus Erythematosus
Active, not recruitingPhase 2
A Study Evaluating the Safety and Efficacy of Inhaled AP01 in Participants With Progressive Pulmonary Fibrosis
Pulmonary Fibrosis, Progressive Pulmonary Fibrosis
RecruitingObservational study
Quantification of Calcinosis Cutis Disease Burden Using Computed Tomography Images
Systemic Sclerosis (SSc), Calcinosis Cutis
RecruitingPhase 1/2
Phase I/II Study of AD-PluReceptor Plus Tafasitamab-cxix and Lymphodepleting Chemotherapy in Patients With Autoimmune Disorders
Autoimmune Disorders, Systemic Sclerosis
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.
Cristiane Kayser principal investigator
Associate Professor
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Probiotic in people with Systemic Sclerosis and Scleroderma, run by Federal University of São Paulo at 1 site in Brazil.
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 3 inclusion and 2 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 27 Nov 2014. 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 Brazil. 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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 Thais Marighela (55-11-55764239, thais_fm@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in the gastrointestinal symptoms as measured by the "The University of California Los Angeles Scleroderma Clinical Trials Consortium Gastrointestinal Tract 2.0 (GIT 2.0)" Questionnaire (time frame: baseline and eight weeks). 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 NCT02302352, which also lists 1 linked publication.
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 27 Nov 2014.