Prebiotics and Metformin Improve Gut and Hormones in Type 2 Diabetes in Youth (MIGHTY-fiber)

Phase 2

Completed

Conditions: Diabetes

Interventions: Dietary Supplement: Biomebliss
Drug: Metformin
Dietary Supplement: Placebo

Registration Number: NCT04209075

Lead Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Brief Summary: Background:

Metformin is a pill youth with type 2 diabetes take. It can cause side effects like diarrhea and upset stomach. Researchers want to see if a fiber supplement can help decrease these side effects.

Objective:

To see if a prebiotic fiber supplement helps improve the gastrointestinal side effects of people taking metformin and helps with their blood sugars.

Eligibility:

People ages 10-25 with type 2 diabetes who are taking or will take metformin

Design:

Participants will be screened with:

Physical exam

Medical history

Blood and urine tests

Meeting with a nutritionist

Participants will stop taking all diabetes medication for 1 week. They will then take metformin by mouth for 1 week. They will be randomly assigned to take either a fiber supplement or a placebo by mouth during the same week. They will then stop all study treatments for 2-3 weeks. Then they will restart metformin for 1 week. The groups that received the fiber versus the placebo will be reversed. All participants will then continue taking metformin and take the fiber for 1 month.

Participants will have 6 visits over about 2 months. These will include:

Blood and urine tests

Meal tests: A plastic tube will be inserted in the participant s arm vein for blood draws. They will drink a special meal.

Dual-energy x-ray absorptiometry (DXA) scan: Participants will lie on their back while the scan measures their body fat and muscle.

While they are home, participants will:

Fill out daily surveys online

Wear daily activity and blood sugar monitors

Collect their stool

Eat only certain foods for two 1-week periods...

Detailed Description: Metformin is the most widely prescribed anti-diabetes medication in the world and the first-line therapy for treating type 2 diabetes (T2D) in youth and adults. However, metformin s glucose-lowering ability is variable in clinical practice, and efficacy is further limited by poor medication adherence because of metformin-associated adverse effects. Gastrointestinal (GI) symptoms such as bloating, abdominal discomfort, cramping, and diarrhea are the most common side effects associated with metformin use occurring in up to 80% of individuals at drug initiation and up to 30% in individuals on chronic treatment. In youth with type 2 diabetes, the burden of metformin-associated side effects is high because metformin is the only oral FDA-approved for treatment and there are no other oral alternatives. Therefore, identifying ways to mitigate these GI side effects, especially in youth with type 2 diabetes, is of high clinical significance. New data suggest that metformin-induced changes in the gut and/ or the microbiome may be related to both its beneficial (glucose-lowering) and adverse effects. To address this clinical challenge, prebiotic fibers that are non-digestible food ingredients, may help to improve metformin tolerability by increasing beneficial bacteria and stool metabolites, such as short chain fatty acid (SCFA) stool concentrations. This pilot study will test the hypothesis that a prebiotic microbiome modulator (MM) - containing prebiotic fibers and polyphenols - will reduce GI side effects of metformin at time of initiation and change the stool metabolite profile in youth and young adults with T2D treated with metformin, age 10-25 years who are not on insulin therapy. The 9-week study will have 2 phases and 6 outpatient visits at the NIH Clinical Center. Phase 1 is a 5-week randomized double blind cross-over trial with two 1-week intervention periods (metformin + prebiotic and metformin + placebo) during which subjects will eat a standardized diet. Phase 2 will occur immediately following phase 1 in which participants will start an open-label 4-week intervention with metformin and the prebiotic MM.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 6

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Prebiotic then Placebo	Placebo	Participant will take Prebiotic during Period 1 and Placebo during Period 2
Prebiotic then Placebo	Biomebliss	Participant will take Prebiotic during Period 1 and Placebo during Period 2
Placebo then Prebiotic	Biomebliss	Participant will take Placebo during Period 1 and Prebiotic during Period 2
Placebo then Prebiotic	Placebo	Participant will take Placebo during Period 1 and Prebiotic during Period 2
Placebo then Prebiotic	Metformin	Participant will take Placebo during Period 1 and Prebiotic during Period 2
Prebiotic then Placebo	Metformin	Participant will take Prebiotic during Period 1 and Placebo during Period 2

Primary Outcome Measures

Name	Time	Method
Gastrointestinal (GI) Tolerability Score	1 week (assessed daily for 7 days)	A composite tolerability score based on 4 GI side effect profile categories (stool consistency, urgency to evacuate, bloating sensation, and flatulence), assessed by daily survey, will be calculated using a principal components analysis. A scale range of GI tolerability score is (1.14, 3.3). A higher tolerability score indicates a lower side effect profile

Secondary Outcome Measures

Name	Time	Method
Stool Short Chain Fatty Acids (SCFA)	1 week and 4 weeks	Stool SCFA, including propionate and butyrate, will be measured in stool samples. SCFAs are microbial metabolites that are gut mediators of metabolism.