Modulation of Type 1 Diabetes Susceptibility Through the Use of Probiotics

Modulation of Type 1 Diabetes Susceptibility Through VSL#3 Probiotic-induced Alterations in the Intestinal Microbiota

Investigators aim to further the understanding of environmental factors that underlie the progression to Type 1 diabetes (T1D). Dysbiosis, defined as alterations in intestinal microbiota composition and function, has been hypothesized to increase the risk of developing T1D in those with genetic susceptibility. Dysbiosis may result from modern dietary habits, such as broad consumption of the highly processed Western Diet, or by widespread use of antibiotics. Here, investigators propose to examine the impact of dysbiosis on the endogenous innate inflammation known to exist within families affected by T1D and if probiotic supplementation may beneficially modulate this inflammatory state.

Participants will be asked to take the probiotic VSL#3 daily for six weeks. Stool and blood samples will be analyzed before and after the six week course of probiotics.

Study Overview

• Status: Completed
• Conditions: Type1diabetes; Type1 Diabetes Mellitus
• Intervention / Treatment: Dietary supplement: VSL#3

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Males and females 5-17 years of age
2. Full-sibling of an individual with a clinical diagnosis of Type 1 diabetes
3. Treatment naïve of any immunomodulatory agent
4. Naïve of any probiotic supplement within the past 12 months

Exclusion Criteria:

1. Presence of severe/active disease that interferes with dietary intake
2. Chronic use of medications known to affect gastrointestinal function, such as stool softeners or laxatives
3. Diagnosis of celiac disease and/or following a gluten-free diet
4. Presence of significant and sustained gastrointestinal symptoms within the prior 6 weeks (e.g., severe abdominal pain, worsening constipation, diarrhea, or recurrent nausea +/- vomiting)
5. Chronic inflammatory or autoimmune disease with the exception of well-controlled hypothyroidism or intermittent or mild persistent asthma not requiring the use of daily inhaled steroids
6. Use of any medications that could affect intestinal microbiota within the previous 3 months (e.g., antibiotics, prebiotics, or probiotics)
7. Any condition that, in the investigator's opinion, may compromise study participation or may confound the interpretation of the study results
8. Female participants of child-bearing age must not be pregnant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: VSL#3; Participants will be given the probiotic supplement VSL#3, a commercially available product. VSL#3 is taken by mouth, either once or twice daily, and is dispensed in sachets, each containing 450 billion colony forming units of bacterial strains. Participants will undergo a screening visit. They will be asked to provide a stool sample by the next visit. Within 3 weeks they will return with a stool sample and receive the VSL#3 sachets as well as another stool collection kit. After 6 weeks of taking VSL#3, they will return for their final visit, with their stool sample. Blood will be drawn at the second and third visits.

Dietary supplement: VSL#3; VSL#3 is a commercially available probiotic supplement manufactured and distributed by Alfasigma USA, Inc of Covington, Louisiana, USA. As with other probiotics, VSL#3 is considered a supplement and is not FDA-approved or regulated. VSL#3 contains eight probiotic strains: bifidobacteria (B. longum, B. infantis, and B. breve), lactobacilli (L. acidophilus, L. casei, L. bulgaricus, and L. plantarum) and Strepococcus thermophiles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Alterations in Plasma-Induced Transcriptional Analysis	Examine the probiotic-induced alterations in the plasma-induced transcriptional analysis	2 years (study duration)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intestinal Microbiota	Examine the intestinal microbiota, plasma microbial antigen levels as a marker of gut barrier function	2 years (study duration)

Collaborators and Investigators

• Sponsor: Medical College of Wisconsin

Study record dates

Study Major Dates

• Study Start (Actual): April 23, 2018
• Primary Completion (Actual): December 18, 2018
• Study Completion (Actual): December 31, 2018

Study Registration Dates

• First Submitted: January 31, 2018
• First Submitted That Met QC Criteria: January 31, 2018
• First Posted (Actual): February 6, 2018

Study Record Updates

• Last Update Posted (Actual): November 30, 2021
• Last Update Submitted That Met QC Criteria: November 28, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: Siblings
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: 1171017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No