Prebiotics and Metformin Improve Gut and Hormones in Type 2 Diabetes in Youth (MIGHTY-fiber)
Condition: Diabetes
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): Biomebliss; Metformin; Placebo
Intervention type(s): Dietary Supplement; Drug; Dietary Supplement
Intervention description(s): BiomeBliss is a commercially available powder containing prebiotic fiber (inulin and beta glucan), along with blueberry extract providing polyphenols.; Metformin is a commonly used antidiabetic medication, and the only oral medication approved for children and adolescents under 18 years old. Though reasonably effective, gastro-intestinal side effects are common (80% at initiation, and 10-30% after long term use). Metformin dosing at clinically recommended doses will be titrated per protocol during the study.; Placebo Comparator
Intervention MeSH terms: Metformin
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Metformin; Type 2 Diabetes; Youth; Microbiome; Gastrointestinal Side Effects