Clinical trial NCT04335656: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Type 1 Diabetes
type1diabetes
Type 1 Diabetes Mellitus
Keywords: New onset
Newly diagnosed
Recent onset
Probiotic
Lactiplantibacillus plantarum
Lp299v
Lead sponsor: Medical College of Wisconsin
Sponsor class: OTHER
First posted: 2020-04-06
Enrollment: 60
Sex: ALL
Minimum age (years): 3
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-blind, placebo-controlled, 2:1 randomly assigned
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: Inclusion Criteria:

1. ≤ 100 days from T1D diagnosis based on ADA criteria
2. \> 21 days from T1D diagnosis or metabolically stable per study physician assessment
3. Males and females 3-45 years of age, inclusive, at time of screening visit
4. Peak MMTT stimulated C-peptide ≥ 0.2 nmol/L
5. 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
6. 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
7. 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:

1. Probiotic supplement use within the past month
2. Antibiotic use within the past month
3. Concurrent or recent (within the past 30 days of screening) use of non-insulin therapies aimed to control hyperglycemia
4. Females who are pregnant or lactating
5. Chronic inflammatory or autoimmune disease with exception of stable thyroid disease
6. 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.)
7. Use of glucocorticoids or other immunosuppressive agents within 30 days of screening MMTT
8. Use of medications known to influence glucose tolerance
9. Dairy allergy
10. Any condition that, in the investigator's opinion, may compromise study participation or may confound the interpretation of the study results.

Primary outcomes:
measure: Change in composite inflammatory index after probiotic supplementation
timeFrame: 5 years (duration of study)
Secondary outcomes:
measure: Rate of stimulated C-peptide Area Under the Curve (AUC) decline after probiotic supplementation
timeFrame: 5 years (duration of study)
measure: Markers of beta cell function
timeFrame: 5 years (duration of study)
measure: Microbial composition as measured by 16s rRNA sequencing
timeFrame: 5 years (duration of study)
measure: Markers of systemic microbial antigen exposure
timeFrame: 5 years (duration of study)
measure: Regulatory T cell abundance and activity by flow cytometry
timeFrame: 5 years (duration of study)
measure: Monocyte abundance and activity by flow cytometry
timeFrame: 5 years (duration of study)
measure: scRNA-seq analyses of peripheral blood mononuclear cells
timeFrame: 5 years (duration of study)
Other outcomes:
Locations:
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
References: