Role of Methane in Glycemic Control

NCT01638429 | Completed Early Phase 1 Results

• 1 other identifier: 25182
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Diabetes; Obesity

Outcome Measures

Primary Outcomes (7)

• Number of Subjects Who Eradicated Methane on Breath Test

  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.

  Baseline and 1-14 days following completion of antibiotic treatment

• Stool Methanogen Levels

  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)

  Baseline and 1-60 days following completion of antibiotic treatment

• Stool Total Bacteria Levels

  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)

  Baseline and 1-60 days following completion of antibiotic treatment

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

  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)

  Baseline and 1-60 days following completion of antibiotic treatment

• Total Cholesterol Levels Before and After Antibiotic Therapy

  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)

  Baseline and 1-60 days following completion of antibiotic treatment

• Average Daily Caloric Loss in Stool

  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)

  Baseline and 1-60 days following completion of antibiotic treatment

• Gastric Emptying

  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)

  Baseline and 1-60 days following completion of antibiotic treatment

Secondary Outcomes (6)

• Bowel Symptoms - Bloating

  Baseline and 1-60 days following completion of antibiotic treatment

• Bowel Symptoms - Abdominal Pain

  Baseline and 1-60 days following completion of antibiotic treatment

• Bowel Symptoms - Constipation

  Baseline and 1-60 days following completion of antibiotic treatment

• Bowel Symptoms - Diarrhea

  Baseline and 1-60 days following completion of antibiotic treatment

• Bowel Symptoms - Straining

  Baseline and 1-60 days following completion of antibiotic treatment

Study Arms (1)

Obese/overweight, prediabetic methane positive

EXPERIMENTAL

Neomycin Rifaximin

Drug: Neomycin; Drug: Rifaximin

Interventions

Neomycin DRUG

Neomycin: 500mg po bid for 10 days

Obese/overweight, prediabetic methane positive

Rifaximin DRUG

Rifaximin: 550mg po tid for 10 days

Obese/overweight, prediabetic methane positive

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Cedars-Sinai Medical Center: lead
• American Diabetes Association: collaborator

Study Sites (1)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus; Obesity

Interventions

Neomycin; Rifaximin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Aminoglycosides; Glycosides; Carbohydrates; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Dr Ruchi Mathur
• Organization: Cedars-Sinai Medical Center

Ruchi.Mathur@cshs.org

310-423-4774

Study Officials

• Ruchi Mathur, MD

  Cedars-Sinai Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Clinical Diabetes Outpatient Treatment and Education Center

Study Record Dates

• First Submitted: April 30, 2012
• First Posted: July 11, 2012
• Study Start: April 1, 2012
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: May 2, 2019
• Results First Posted: May 2, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)