Back to resultsReducing Innate Inflammation in New Onset Type 1 Diabetes
Primary Purpose
Type 1 Diabetes, type1diabetes, Type 1 Diabetes Mellitus
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Lactiplantibacillus plantarum
Placebo
Sponsored by
About this trial
This is an interventional basic science trial for Type 1 Diabetes focused on measuring New onset, Newly diagnosed, Recent onset, Probiotic, Lactiplantibacillus plantarum, Lp299v
Eligibility Criteria
Inclusion Criteria:
- ≤ 100 days from T1D diagnosis based on ADA criteria
- > 21 days from T1D diagnosis or metabolically stable per study physician assessment
- Males and females 3-45 years of age, inclusive, at time of screening visit
- Peak MMTT stimulated C-peptide ≥ 0.2 nmol/L
- Positive for at least 1 diabetes autoantibody (excluding mIAA in those who have received ≥ 2 weeks of exogenous insulin therapy) either through clinically obtained labs at time of diagnosis or as obtained at the screening visit
- Females of child-bearing potential (defined as any female who has reached menarche (first menses), excluding those who have had a hysterectomy or are post-menopausal and must be willing to use effective birth control (which may include abstinence)) from screening visit until final study visit
- Willing and able to give informed consent or have parent or legal guardian provide informed consent if the subject is < 18 years of age
Exclusion Criteria:
- Probiotic supplement use within the past month
- Antibiotic use within the past month
- Concurrent or recent (within the past 30 days of screening) use of non-insulin therapies aimed to control hyperglycemia
- Females who are pregnant or lactating
- Chronic inflammatory or autoimmune disease with exception of stable thyroid disease
- Uncontrolled celiac disease (i.e., consuming gluten) or actively being evaluated for possible celiac disease (i.e., clinically obtained tissue transglutaminase IgA titers above reference range, being referred to gastroenterology for possible endoscopy, etc.)
- Use of glucocorticoids or other immunosuppressive agents within 30 days of screening MMTT
- Use of medications known to influence glucose tolerance
- Dairy allergy
- Any condition that, in the investigator's opinion, may compromise study participation or may confound the interpretation of the study results.
Sites / Locations
- Medical College of WisconsinRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Treatment Group
Placebo Group
Arm Description
Subjects will be randomized to the treatment or placebo group. The treatment is a capsule taken by mouth once a day for 6 months.
Subjects will be randomized to the treatment or placebo group. The placebo is a capsule taken by mouth once a day for 6 months.
Outcomes
Primary Outcome Measures
Change in composite inflammatory index after probiotic supplementation
Investigators will examine the effect of probiotic supplementation on the endogenous innate inflammatory state in youth newly diagnosed with T1D, as measured by plasma-induced transcription and analyzed using a composite inflammatory index score. The investigators hypothesize that the subjects receiving the probiotic will have less inflammation (as measured by transcriptional analysis) than the participants in the placebo group.
Secondary Outcome Measures
Rate of stimulated C-peptide Area Under the Curve (AUC) decline after probiotic supplementation
Investigators will examine the rate of C-peptide decline, as measured by C-peptide AUC in youth newly diagnosed with T1D. The investigators hypothesize that the subjects receiving the probiotic for 6 months will have a slower rate of decline than the subjects in the placebo group.
Markers of beta cell function
Investigators will examine the effect of probiotic supplementation on beta cell function by measuring proinsulin levels, ratio of proinsulin to C-peptide and islet amyloid polypeptide to pro-islet amyloid polypeptide ratio.
Microbial composition as measured by 16s rRNA sequencing
Investigators will examine the effect of probiotic supplementation using 16s rRNA sequencing to determine the composition of the intestinal microbiota. Investigators hypothesize the composition of the intestinal microbiota will differ before and after treatment with probiotic supplementation.
Markers of systemic microbial antigen exposure
Gut leakiness will be measured by examining the levels of microbial antigens in the plasma before and after treatment and correlating these antigen levels with the changes in the composition of the gut bacteria. It is hypothesized that changes in antigen levels and gut bacteria will only be seen in the participants receiving the probiotic. It is further hypothesized that those with the greatest reduction in antigens will have the most significant changes in gut bacteria composition.
Regulatory T cell abundance and activity by flow cytometry
Investigators will examine the effect of probiotic supplementation on regulatory T cell abundance and activity.
Monocyte abundance and activity by flow cytometry
Investigators will examine the effect of probiotic supplementation on monocyte abundance and activity.
scRNA-seq analyses of peripheral blood mononuclear cells
Investigators will examine the effect of probiotic supplementation on peripheral blood mononuclear cells using single cell RNA sequencing analysis.
Full Information
NCT ID
NCT04335656
First Posted
March 27, 2020
Last Updated
October 18, 2023
Sponsor
Medical College of Wisconsin
1. Study Identification
Unique Protocol Identification Number
NCT04335656
Brief Title
Reducing Innate Inflammation in New Onset Type 1 Diabetes
Official Title
Reducing Innate Inflammation in New Onset Type 1 Diabetes With Lactiplantibacillus Plantarum
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 1, 2021 (Actual)
Primary Completion Date
May 31, 2025 (Anticipated)
Study Completion Date
December 31, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Medical College of Wisconsin
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study aims to determine whether Lactiplantibacillus plantarum 299v (Lp299v) supplementation will reduce systemic inflammation and prolong residual beta cell function in individuals newly diagnosed with Type 1 diabetes. The investigators hypothesize that probiotic-induced alterations in the intestinal microbiota may favorably alter the post-onset disease state.
Detailed Description
For individuals newly diagnosed with Type 1 diabetes, this clinical trial will assess whether probiotic supplementation has efficacy in reducing the endogenous systemic innate inflammatory state known to exist in newly diagnosed Type 1 diabetes and whether this reduction correlates with preservation of endogenous insulin production as measured by stimulated C-peptide during mixed meal tolerance testing (MMTT). The innate inflammatory state will be measured by plasma-induced transcriptional assay and quantified as a composite inflammatory index. Mixed meal tolerance testing is the gold standard measure of endogenous insulin production. During this test, serial blood c-peptide levels are collected over 2 hours in response to challenge with a nutritional drink containing a mix of protein, fat, and carbohydrate and the C-peptide area under the curve is calculated.
Using a randomized, placebo-controlled design, the investigators will measure changes in systemic inflammation (primary outcome) and beta cell function (secondary outcome) after six months of daily treatment with either Lp299v supplementation or placebo. These measures of plasma-induced transcriptional assay and MMTT will be related to markers of beta cell stress, the composition of the gut microbiota, analysis of the plasma metabolome, and levels of microbial antigen exposure.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 1 Diabetes, type1diabetes, Type 1 Diabetes Mellitus
Keywords
New onset, Newly diagnosed, Recent onset, Probiotic, Lactiplantibacillus plantarum, Lp299v
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Double-blind, placebo-controlled, 2:1 randomly assigned
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Treatment Group
Arm Type
Experimental
Arm Description
Subjects will be randomized to the treatment or placebo group. The treatment is a capsule taken by mouth once a day for 6 months.
Arm Title
Placebo Group
Arm Type
Placebo Comparator
Arm Description
Subjects will be randomized to the treatment or placebo group. The placebo is a capsule taken by mouth once a day for 6 months.
Intervention Type
Dietary Supplement
Intervention Name(s)
Lactiplantibacillus plantarum
Other Intervention Name(s)
Lp299v
Intervention Description
Probiotic capsule in powder form, which can be swallowed or opened and contents sprinkled on cold foods or beverages
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo capsule in powder form, which can be swallowed or opened and contents sprinkled on cold foods or beverages
Primary Outcome Measure Information:
Title
Change in composite inflammatory index after probiotic supplementation
Description
Investigators will examine the effect of probiotic supplementation on the endogenous innate inflammatory state in youth newly diagnosed with T1D, as measured by plasma-induced transcription and analyzed using a composite inflammatory index score. The investigators hypothesize that the subjects receiving the probiotic will have less inflammation (as measured by transcriptional analysis) than the participants in the placebo group.
Time Frame
5 years (duration of study)
Secondary Outcome Measure Information:
Title
Rate of stimulated C-peptide Area Under the Curve (AUC) decline after probiotic supplementation
Description
Investigators will examine the rate of C-peptide decline, as measured by C-peptide AUC in youth newly diagnosed with T1D. The investigators hypothesize that the subjects receiving the probiotic for 6 months will have a slower rate of decline than the subjects in the placebo group.
Time Frame
5 years (duration of study)
Title
Markers of beta cell function
Description
Investigators will examine the effect of probiotic supplementation on beta cell function by measuring proinsulin levels, ratio of proinsulin to C-peptide and islet amyloid polypeptide to pro-islet amyloid polypeptide ratio.
Time Frame
5 years (duration of study)
Title
Microbial composition as measured by 16s rRNA sequencing
Description
Investigators will examine the effect of probiotic supplementation using 16s rRNA sequencing to determine the composition of the intestinal microbiota. Investigators hypothesize the composition of the intestinal microbiota will differ before and after treatment with probiotic supplementation.
Time Frame
5 years (duration of study)
Title
Markers of systemic microbial antigen exposure
Description
Gut leakiness will be measured by examining the levels of microbial antigens in the plasma before and after treatment and correlating these antigen levels with the changes in the composition of the gut bacteria. It is hypothesized that changes in antigen levels and gut bacteria will only be seen in the participants receiving the probiotic. It is further hypothesized that those with the greatest reduction in antigens will have the most significant changes in gut bacteria composition.
Time Frame
5 years (duration of study)
Title
Regulatory T cell abundance and activity by flow cytometry
Description
Investigators will examine the effect of probiotic supplementation on regulatory T cell abundance and activity.
Time Frame
5 years (duration of study)
Title
Monocyte abundance and activity by flow cytometry
Description
Investigators will examine the effect of probiotic supplementation on monocyte abundance and activity.
Time Frame
5 years (duration of study)
Title
scRNA-seq analyses of peripheral blood mononuclear cells
Description
Investigators will examine the effect of probiotic supplementation on peripheral blood mononuclear cells using single cell RNA sequencing analysis.
Time Frame
5 years (duration of study)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
3 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
≤ 100 days from T1D diagnosis based on ADA criteria
> 21 days from T1D diagnosis or metabolically stable per study physician assessment
Males and females 3-45 years of age, inclusive, at time of screening visit
Peak MMTT stimulated C-peptide ≥ 0.2 nmol/L
Positive for at least 1 diabetes autoantibody (excluding mIAA in those who have received ≥ 2 weeks of exogenous insulin therapy) either through clinically obtained labs at time of diagnosis or as obtained at the screening visit
Females of child-bearing potential (defined as any female who has reached menarche (first menses), excluding those who have had a hysterectomy or are post-menopausal and must be willing to use effective birth control (which may include abstinence)) from screening visit until final study visit
Willing and able to give informed consent or have parent or legal guardian provide informed consent if the subject is < 18 years of age
Exclusion Criteria:
Probiotic supplement use within the past month
Antibiotic use within the past month
Concurrent or recent (within the past 30 days of screening) use of non-insulin therapies aimed to control hyperglycemia
Females who are pregnant or lactating
Chronic inflammatory or autoimmune disease with exception of stable thyroid disease
Uncontrolled celiac disease (i.e., consuming gluten) or actively being evaluated for possible celiac disease (i.e., clinically obtained tissue transglutaminase IgA titers above reference range, being referred to gastroenterology for possible endoscopy, etc.)
Use of glucocorticoids or other immunosuppressive agents within 30 days of screening MMTT
Use of medications known to influence glucose tolerance
Dairy allergy
Any condition that, in the investigator's opinion, may compromise study participation or may confound the interpretation of the study results.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Susanne Cabrera, MD
Phone
414-955-4903
Email
T1dinfo@mcw.edu
Facility Information:
Facility Name
Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Susanne Cabrera, MD
Phone
414-955-4903
Email
t1dinfo@mcw.edu
12. IPD Sharing Statement
Plan to Share IPD
No
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Reducing Innate Inflammation in New Onset Type 1 Diabetes
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