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

NCT04209075 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 20001820-DK-0018
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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...

Conditions

Diabetes

Keywords

Metformin; Type 2 Diabetes; Youth; Microbiome; Gastrointestinal Side Effects

Outcome Measures

Primary Outcomes (1)

• Gastrointestinal (GI) Tolerability Score

  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

  1 week (assessed daily for 7 days)

Secondary Outcomes (1)

• Stool Short Chain Fatty Acids (SCFA)

  1 week and 4 weeks

Study Arms (2)

Placebo then Prebiotic

EXPERIMENTAL

Participant will take Placebo during Period 1 and Prebiotic during Period 2

Dietary Supplement: Biomebliss; Drug: Metformin; Dietary Supplement: Placebo

Prebiotic then Placebo

EXPERIMENTAL

Participant will take Prebiotic during Period 1 and Placebo during Period 2

Dietary Supplement: Biomebliss; Drug: Metformin; Dietary Supplement: Placebo

Interventions

Biomebliss DIETARY_SUPPLEMENT

BiomeBliss is a commercially available powder containing prebiotic fiber (inulin and beta glucan), along with blueberry extract providing polyphenols.

Placebo then Prebiotic; Prebiotic then Placebo

Metformin DRUG

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 then Prebiotic; Prebiotic then Placebo

Placebo DIETARY_SUPPLEMENT

Placebo Comparator

Placebo then Prebiotic; Prebiotic then Placebo

Eligibility Criteria

• Age: 10 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age 10-25 years
• Pubertal or post-pubertal: Girls - Tanner stage IV-V breast; Boys - Testicular volume \>10cc
• Diagnosis of type 2 diabetes by American Diabetes Association (ADA) guidelines \[36\] or with established diagnosis previously treated with metformin.
• Negative test for diabetes-related autoantibodies (glutamic acid decarboxylase 65 and tyrosine phosphatase-related islet antigen 2 (IA-2)) documented in NIH CRIS chart or via outside laboratory assessment within the last 10 years.
• Hemoglobin A1C \<8% at study initiation

You may not qualify if:

• Pregnancy or breastfeeding
• Allergy to study medications
• Allergy or self-reported intolerance to blueberry, pomegranate, or oats, soy, gluten or dairy products.
• Chronic insulin therapy or insulin use within the last 3 months
• Treatment with other medications which are known to affect the parameters under study, including antibiotics within the last month, immunosuppressants, proton-pump inhibitors, supraphysiologic systemic steroids, probiotic or prebiotic supplements
• Heavy yogurt consumption (2 or more servings of \>=6 oz per day)
• Chronic GI disease, gastric bypass surgery, cancer diagnosis or autoimmune disease
• Metabolic derangement such as metabolic acidosis, severe hyperglycemia (fasting blood glucose \>= 200mg/dL), and/or liver enzymes \> three times the upper limit of normal.
• Any other condition that, in the opinion of the investigators, will increase risk to the subject, or impede the
• accurate collection of study-related data.
• Body weight \>= 450lbs
• Body weight \<=58kg
• Hemoglobin concentration \<10g/dL

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (2)

• Burton JH, Johnson M, Johnson J, Hsia DS, Greenway FL, Heiman ML. Addition of a Gastrointestinal Microbiome Modulator to Metformin Improves Metformin Tolerance and Fasting Glucose Levels. J Diabetes Sci Technol. 2015 Jul;9(4):808-14. doi: 10.1177/1932296815577425. Epub 2015 Mar 23.

  PMID: 25802471 BACKGROUND

• Dixon SA, Mishra S, Dietsche KB, Jain S, Mabundo L, Stagliano M, Krenek A, Courville A, Yang S, Turner SA, Meyers AG, Estrada DE, Yadav H, Chung ST. The effects of prebiotics on gastrointestinal side effects of metformin in youth: A pilot randomized control trial in youth-onset type 2 diabetes. Front Endocrinol (Lausanne). 2023 Feb 23;14:1125187. doi: 10.3389/fendo.2023.1125187. eCollection 2023.

  PMID: 36909343 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Diabetes Mellitus; Diabetes Mellitus, Type 2

Interventions

Metformin

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: Dr. Stephanie Chung
• Organization: NIDDK

Stephanie.Chung@NIH.gov

301-402-2122

Study Officials

• Stephanie T Chung, M.D.

  National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2019
• First Posted: December 23, 2019
• Study Start: March 10, 2020
• Primary Completion: July 15, 2021
• Study Completion: July 15, 2021
• Last Updated: August 30, 2022
• Results First Posted: August 30, 2022

Record last verified: 2021-08

Locations

US (1)