DiabetesPhase 2NCT04209075
Prebiotics and Metformin Improve Gut and Hormones in Type 2 Diabetes in Youth (MIGHTY-fiber)
A Phase 2 study testing Biomebliss and Metformin in people with Diabetes, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 10 to 25 years
- Conditions the study is for
- Diabetes
- What is being tested?
- Biomebliss and Metformin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Mar 2020to 15 Jul 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 10 to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 13Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Prebiotics and Metformin Influences Gut and Hormones in Type 2 Diabetes Youth (MIGHTY)
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.
Read more
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...
Read the 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.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BiomeblissDietary supplement
BiomeBliss is a commercially available powder containing prebiotic fiber (inulin and beta glucan), along with blueberry extract providing polyphenols.
MetforminDrug
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.
PlaceboDietary supplement
Placebo Comparator
| Study group | Role | What they receive |
|---|---|---|
| Placebo then Prebiotic | Experimental | Participant will take Placebo during Period 1 and Prebiotic during Period 2 Receives: Dietary Supplement: Biomebliss; Drug: Metformin; Dietary Supplement: Placebo |
| Prebiotic then Placebo | Experimental | Participant will take Prebiotic during Period 1 and Placebo during Period 2 Receives: Dietary Supplement: Biomebliss; Drug: Metformin; Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 1 week (assessed daily for 7 days)
Secondary outcomes (1)
Stool Short Chain Fatty Acids (SCFA)
Stool SCFA, including propionate and butyrate, will be measured in stool samples. SCFAs are microbial metabolites that are gut mediators of metabolism.
Measured: 1 week and 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2019
- Study start10 Mar 2020
- Primary completion15 Jul 2021
- Study completion15 Jul 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for DiabetesStudies of the same condition, open and under way.
- More trials run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Stephanie T Chung, M.D., Principal investigator, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04209075
- Sponsor's protocol ID
- 200018
- Other IDs
- 20-DK-0018
- Status last verified
- Aug 2021
- First submitted
- 20 Dec 2019
- Last updated
- 30 Aug 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 25802471Dixon 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.
PubMed 36909343
Study at a glance
From the registry record, last updated by the sponsor on 30 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prebiotics and Metformin Influences Gut and Hormones in Type 2 Diabetes Youth (MIGHTY)
- ClinicalTrials.gov ID
- NCT04209075
- Acronym / sponsor ID
- 200018
- Conditions
- Diabetes
- Keywords
- Metformin, Type 2 Diabetes, Youth, Microbiome, Gastrointestinal Side Effects
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)US National Institutes of Health
- Study start
- 10 Mar 2020 (actual)
- Primary completion
- 15 Jul 2021 (actual)
- Study completion
- 15 Jul 2021 (actual)
- First posted
- 23 Dec 2019 (actual)
- Results
- Posted 30 Aug 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo then Prebiotic | Experimental | Dietary Supplement: Biomebliss, Drug: Metformin, Dietary Supplement: PlaceboParticipant will take Placebo during Period 1 and Prebiotic during Period 2 |
| Prebiotic then Placebo | Experimental | Dietary Supplement: Biomebliss, Drug: Metformin, Dietary Supplement: PlaceboParticipant will take Prebiotic during Period 1 and Placebo during Period 2 |
Who may qualify
- Ages
- 10 to 25 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BiomeblissBiomeBliss is a commercially available powder containing prebiotic fiber (inulin and beta glucan), along with blueberry extract providing polyphenols. | Dietary supplement | Placebo then Prebiotic, Prebiotic then Placebo |
| MetforminMetformin 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. | Drug | Placebo then Prebiotic, Prebiotic then Placebo |
| PlaceboPlacebo Comparator | Dietary supplement | Placebo then Prebiotic, Prebiotic then Placebo |
Primary outcome
Gastrointestinal (GI) Tolerability Score
Time frame: 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
1 secondary outcome
Stool Short Chain Fatty Acids (SCFA)
Time frame: 1 week and 4 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Aug 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 25802471Burton 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.
- Derived from this study: PubMed 36909343Dixon 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.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stephanie T Chung, M.D. principal investigator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Biomebliss and Metformin in people with Diabetes, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Aug 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Gastrointestinal (GI) Tolerability Score (time frame: 1 week (assessed daily for 7 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04209075, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Aug 2022.