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NCT Number: NCT01638429

Role of Methane in Glycemic Control

The purpose of this study is to determine how certain types of bacteria in the human gut may affect weight gain, and contribute to the development of diabetes.

The investigators initial studies have shown that gut bacteria that produce methane may directly affect weight gain. These bacteria, called methanogens, produce methane gas as a byproduct, which can be detected through breath testing. Methane can slow the passage of food through the intestines, which would allow extra time for uptake and absorption of nutrients and calories, and might contribute to weight gain. The investigators have also found that people who have increased levels of methane-producing bacteria in their intestines also have higher levels of glucose in their blood. Therefore, control of how the body responds to insulin and uses glucose may be altered in methane-producing individuals.

This research study is designed to test the investigational use of the drugs neomycin and rifaximin that have been approved by the U.S Food and Drug Administration (FDA). While neomycin is FDA-approved for treating skin infections, preparing the bowel for surgery, and hepatic encephalopathy (a condition that occurs when a damaged liver cannot remove the toxins that a healthy liver normally would), and rifaximin is FDA-approved for treating travelers' diarrhea, they are not yet approved to be used together for the treatment of methanogens or obesity.

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Key information

Conditions

Diabetes Body Weight Diabetes Mellitus Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases Nutrition Disorders Nutritional and Metabolic Diseases Obesity Overnutrition Overweight Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Early Phase 1

Primary location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

About this study

Pre-diabetes is defined by impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) and affects more than 40% of US adults. While glycemic dysregulation and insulin resistance are central to the progression from pre-diabetes to diabetes, obesity also plays a key role. Research has begun to define the relationship between gut flora, metabolism and weight gain. Animal studies have linked a specific methanogen, Methanobrevibacter smithii, to weight gain, and in humans we have found that increased methane on breath test is associated both with increased body mass index (BMI) and higher blood glucose levels. We also found that methane gas directly slows gut transit by 59% in an in vivo animal model. We hypothesize that this slowing of transit could result in a greater time to harvest nutrients and absorb calories, representing a potential mechanism for elevated post-prandial glycemic excursions and weight gain. In this study, we will test this hypothesis by determining the effects of enteric methane production on glucose excursions, gut transit and energy utilization in obese or overweight, prediabetic, adult subjects.

We will explore the relationship between methane, M. smithii, obesity and gut transit in human subjects using objective measures of metabolic function, glucose excursions, energy utilization and transit studies, to evaluate whether intestinal methane production is associated with a higher incidence of diabetes risk in an obese study population. We will then repeat testing following a course of antibiotics known to eliminate methanogens. This will potentially provide novel therapies for the pre-diabetic patient, and allow new avenues for research.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 18-65 years old with pre-diabetes (hemoglobin a1c of 5.7-6.4%)
  • BMI > 25.0
  • presence of methane on a breath sample (>3ppm)

Exclusion criteria

Subjects will be excluded from the study if they exhibit any of the following:

  • Diabetes/diabetes medications
  • Prokinetic medication
  • Pregnancy
  • History of bariatric or intestinal surgery (other than cholecystectomy or appendectomy)
  • Unstable thyroid disease
  • An active weight loss treatment/plan
  • Smoking
  • Dietary restrictions (lactose intolerance, vegan etc)
  • Other inability to comply with the study procedures, including known allergy to the study antibiotics (neomycin and rifaximin)
  • Active inflammatory bowel disease (celiac, Crohn's disease, ulcerative colitis)
  • Antibiotic use in the past month
  • Subjects who do not have a microwave (for reheating study meals) and a freezer (for storing leftovers and stool samples) will be excluded from this study.
  • Subjects who have an aspirin sensitivity
  • Proton pump inhibitor medications or antacids
  • History of bezoar
  • Disorders of swallowing
  • Suspected strictures, fistulas or physiological GI obstruction
  • GI surgery within 3 months
  • Severe dysphagia to food or pills
  • Diverticulitis
  • Subjects who use an implanted or portable electromechanical device such as a cardiac pacemaker or infusion pump
  • Subject who have a peanut allergy

Treatment and study plan

Neomycin

Drug

Neomycin: 500mg po bid for 10 days

Rifaximin

Drug

Rifaximin: 550mg po tid for 10 days

Primary outcomes

  1. Number of Subjects Who Eradicated Methane on Breath Test

    Time frame: Baseline and 1-14 days following completion of antibiotic treatment

    Number of subjects who exhibited a decrease in breath methane levels to below detectable (below 3ppm) following antibiotic treatment.

    After baseline (pre-treatment) testing, subjects underwent a 10-day course of antibiotics. Post-treatment breath tests were performed within 2 weeks (14 days) of completing the course of antibiotics.

  2. Stool Methanogen Levels

    Time frame: Baseline and 1-60 days following completion of antibiotic treatment

    Stool methanogen levels were measured in all subjects before and after antibiotic treatment. After baseline (pre-treatment) testing, subjects underwent a 10-day course of antibiotics. Post-treatment stool samples were collected within 31 days (1 month) of completing the course of antibiotics. One subject received an exemption from this requirement and completed testing within 60 days.

    For analysis, subjects were grouped into two groups:

    Group 1 - Methane Eradicators (subjects who eradicated methane on breath test following antibiotic treatment) (N=8) Group 2 - Methane Non-eradicators (subjects who did not eradicate methane on breath test following antibiotic treatment) (N=3)

  3. Stool Total Bacteria Levels

    Time frame: Baseline and 1-60 days following completion of antibiotic treatment

    Stool total bacteria levels were measured in all subjects before and after antibiotic treatment. After baseline (pre-treatment) testing, subjects underwent a 10-day course of antibiotics.Post-treatment stool samples were collected within 31 days (1 month) of completing the course of antibiotics. One subject received an exemption from this requirement and completed testing within 60 days. For analysis, subjects were grouped into two groups:

    Group 1 - Methane Eradicators (subjects who eradicated methane on breath test following antibiotic treatment) (N=8) Group 2 - Methane Non-eradicators (subjects who did not eradicate methane on breath test following antibiotic treatment) (N=3)

  4. Low Density Lipoprotein (LDL) Levels Before and After Antibiotic Therapy

    Time frame: Baseline and 1-60 days following completion of antibiotic treatment

    LDL levels were measured in all subjects before and after antibiotic treatment. After baseline (pre-treatment) testing, subjects underwent a 10-day course of antibiotics. Post-treatment blood samples were collected within 31 days (1 month) of completing the course of antibiotics. One subject received an exemption from this requirement and completed testing within 60 days.

    For analysis, subjects were grouped into two groups:

    Group 1 - Methane Eradicators (subjects who eradicated methane on breath test following antibiotic treatment) (N=8) Group 2 - Methane Non-eradicators (subjects who did not eradicate methane on breath test following antibiotic treatment) (N=3)

  5. Total Cholesterol Levels Before and After Antibiotic Therapy

    Time frame: Baseline and 1-60 days following completion of antibiotic treatment

    Total cholesterol levels were measured in all subjects before and after antibiotic treatment. After baseline (pre-treatment) testing, subjects underwent a 10-day course of antibiotics.Post-treatment blood samples were collected within 31 days (1 month) of completing the course of antibiotics. One subject received an exemption from this requirement and completed testing within 60 days.

    For analysis, subjects were grouped into two groups:

    Group 1 - Methane Eradicators (subjects who eradicated methane on breath test following antibiotic treatment) (N=8) Group 2 - Methane Non-eradicators (subjects who did not eradicate methane on breath test following antibiotic treatment) (N=3)

  6. Average Daily Caloric Loss in Stool

    Time frame: Baseline and 1-60 days following completion of antibiotic treatment

    The daily caloric loss in stool for each subject was calculated by expressing the total number of kcalories lost in stool over a 3-day period as a percentage of the total number of kcalories ingested over the same 3 days (the number of calories ingested = the number available in meals provided less the number remaining in leftovers). Caloric content for meals, leftovers, and stool was determined by bomb calorimetry. This average daily caloric loss for each group was then compared before and after antibiotic therapy.

    Post-treatment caloric harvest studies were performed within 31 days (1 month) of completing the course of antibiotics. One subject received an exemption from this requirement and completed testing within 60 days. For analysis, subjects were grouped into two groups:

    Group 1 - Total study population (methane eradicators and non-eradicators, N=11) Group 2 - Methane eradicators (subjects who eradicated methane on breath test following antibiotic treatment, N=8)

  7. Gastric Emptying

    Time frame: Baseline and 1-60 days following completion of antibiotic treatment

    Gastric Emptying times (minutes) were determined in all subjects before and after antibiotic treatment. After baseline (pre-treatment) testing, subjects underwent a 10-day course of antibiotics. Post-treatment gastric emptying studies were performed within 31 days (1 month) of completing the course of antibiotics. One subject received an exemption from this requirement and completed testing within 60 days. For analysis, subjects were grouped into two groups:

    Group 1 - Total study population (methane eradicators and non-eradicators, N=11) Group 2 - Methane eradicators (subjects who eradicated methane on breath test following antibiotic treatment, N=8)

Secondary outcomes

  1. Bowel Symptoms - Bloating

    Time frame: Baseline and 1-60 days following completion of antibiotic treatment

    Bowel symptom scores on a visual analog scale (VAS) were compared in all subjects before and after antibiotic treatment. Scale values were from 0 to 100, where 0 indicates no symptom and 100 indicates severe symptoms.

    After baseline (pre-treatment) testing, subjects underwent a 10-day course of antibiotics. Post-treatment symptom scores were obtained within 31 days (1 month) of completing the course of antibiotics. One subject received an exemption from this requirement and completed testing within 60 days. For analysis, subjects were grouped into two groups:

    Group 1 - Total study population (methane eradicators and non-eradicators, N=11) Group 2 - Methane eradicators (subjects who eradicated methane on breath test following antibiotic treatment, N=8)

  2. Bowel Symptoms - Abdominal Pain

    Time frame: Baseline and 1-60 days following completion of antibiotic treatment

    Bowel symptom scores on a visual analog scale (VAS) were compared in all subjects before and after antibiotic treatment. Scale values were from 0 to 100, where 0 indicates no symptom and 100 indicates severe symptoms.

    After baseline (pre-treatment) testing, subjects underwent a 10-day course of antibiotics. Post-treatment symptom scores were obtained within 31 days (1 month) of completing the course of antibiotics. One subject received an exemption from this requirement and completed testing within 60 days. For analysis, subjects were grouped into two groups:

    Group 1 - Total study population (methane eradicators and non-eradicators, N=11) Group 2 - Methane eradicators (subjects who eradicated methane on breath test following antibiotic treatment, N=8)

  3. Bowel Symptoms - Constipation

    Time frame: Baseline and 1-60 days following completion of antibiotic treatment

    Bowel symptom scores on a visual analog scale (VAS) were compared in all subjects before and after antibiotic treatment. Scale values were from 0 to 100, where 0 indicates no symptom and 100 indicates severe symptoms.

    After baseline (pre-treatment) testing, subjects underwent a 10-day course of antibiotics. Post-treatment symptom scores were obtained within 31 days (1 month) of completing the course of antibiotics. One subject received an exemption from this requirement and completed testing within 60 days. For analysis, subjects were grouped into two groups:

    Group 1 - Total study population (methane eradicators and non-eradicators, N=11) Group 2 - Methane eradicators (subjects who eradicated methane on breath test following antibiotic treatment, N=8)

  4. Bowel Symptoms - Diarrhea

    Time frame: Baseline and 1-60 days following completion of antibiotic treatment

    Bowel symptom scores on a visual analog scale (VAS) were compared in all subjects before and after antibiotic treatment. Scale values were from 0 to 100, where 0 indicates no symptom and 100 indicates severe symptoms.

    After baseline (pre-treatment) testing, subjects underwent a 10-day course of antibiotics. Post-treatment symptom scores were obtained within 31 days (1 month) of completing the course of antibiotics. One subject received an exemption from this requirement and completed testing within 60 days. For analysis, subjects were grouped into two groups:

    Group 1 - Total study population (methane eradicators and non-eradicators, N=11) Group 2 - Methane eradicators (subjects who eradicated methane on breath test following antibiotic treatment, N=8)

  5. Bowel Symptoms - Straining

    Time frame: Baseline and 1-60 days following completion of antibiotic treatment

    Bowel symptom scores on a visual analog scale (VAS) were compared in all subjects before and after antibiotic treatment. Scale values were from 0 to 100, where 0 indicates no symptom and 100 indicates severe symptoms.

    After baseline (pre-treatment) testing, subjects underwent a 10-day course of antibiotics. Post-treatment symptom scores were obtained within 31 days (1 month) of completing the course of antibiotics. One subject received an exemption from this requirement and completed testing within 60 days. For analysis, subjects were grouped into two groups:

    Group 1 - Total study population (methane eradicators and non-eradicators, N=11) Group 2 - Methane eradicators (subjects who eradicated methane on breath test following antibiotic treatment, N=8)

  6. % Stool Dry Weight

    Time frame: Baseline and 1-60 days following completion of antibiotic treatment

    % stool dry weight [total stool dry weight (g)/total stool fresh weight (g)] was determined in all subjects before and after antibiotic treatment. After baseline (pre-treatment) testing, subjects underwent a 10-day course of antibiotics. Post-treatment stool samples were obtained within 31 days (1 month) of completing the course of antibiotics. One subject received an exemption from this requirement and completed testing within 60 days. For analysis, subjects were grouped into two groups: Group 1 - Total study population (methane eradicators and non-eradicators, N=11) Group 2 - Methane eradicators (subjects who eradicated methane on breath test following antibiotic treatment, N=8)

Sponsors and collaborators

Lead sponsor

Cedars-Sinai Medical Center

Other

Collaborators

  • American Diabetes Association

Registry information

Official study title

Methane Production and Glycemic Regulation in Pre-diabetic Subjects: Role of Methane in Glycemic Control

Important dates

Study start
2012
Primary completion
2014
Study completion
2014
First posted
Jul 11, 2012
Registry last updated
May 2, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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