Trial Outcomes & Findings for Role of Methane in Glycemic Control (NCT NCT01638429)

NCT ID: NCT01638429

Last Updated: 2019-05-02

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: EARLY_PHASE1
• Target enrollment: 11 participants
• Primary outcome timeframe: Baseline and 1-14 days following completion of antibiotic treatment
• Results posted on: 2019-05-02

Participant Flow

Study was open for recruitment from April 12, 2012 - Dec 31, 2013 Setting: Tertiary care center

A total of 12 subjects were consented to participate. 1 subject withdrew prior to completing the study.

Participant milestones

Measure	Obese/Overweight, Prediabetic Methane Positive Subjects Neomycin Rifaximin Neomycin: Neomycin: 500mg po bid for 10 days Rifaximin: Rifaximin: 550mg po tid for 10 days
Overall Study STARTED	12
Overall Study Pre-treatment Testing	11
Overall Study Antibiotic Treatment	11
Overall Study Post-treatment Testing	11
Overall Study COMPLETED	11
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure	Obese/Overweight, Prediabetic Methane Positive Subjects Neomycin Rifaximin Neomycin: Neomycin: 500mg po bid for 10 days Rifaximin: Rifaximin: 550mg po tid for 10 days
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Role of Methane in Glycemic Control

Baseline characteristics by cohort

Measure	Obese/Overweight, Prediabetic Methane Positive Subjects n=11 Participants Neomycin Rifaximin Neomycin: Neomycin: 500mg po bid for 10 days Rifaximin: Rifaximin: 550mg po tid for 10 days
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	11 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	47 years STANDARD_DEVIATION 9 • n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Region of Enrollment United States	11 participants n=5 Participants
Body Mass Index (BMI)	35.17 kg/m^2 STANDARD_DEVIATION 7.71 • n=5 Participants
A1c (%)	5.72 Percent STANDARD_DEVIATION 0.60 • n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Obese/Overweight, Prediabetic Methane Positive n=11 Participants Neomycin Rifaximin Neomycin: Neomycin: 500mg po bid for 10 days Rifaximin: Rifaximin: 550mg po tid for 10 days	Methane Non-Eradicators Subjects who did not eradicate methane on breath test following antibiotic treatment
Number of Subjects Who Eradicated Methane on Breath Test	8 participants	—

PRIMARY outcome

Timeframe: 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)

Outcome measures

Measure	Obese/Overweight, Prediabetic Methane Positive n=8 Participants Neomycin Rifaximin Neomycin: Neomycin: 500mg po bid for 10 days Rifaximin: Rifaximin: 550mg po tid for 10 days	Methane Non-Eradicators n=3 Participants Subjects who did not eradicate methane on breath test following antibiotic treatment
Stool Methanogen Levels Pre-treatment	3.6*10^7 colony forming units Standard Deviation 9.2*10^7	6.86*10^8 colony forming units Standard Deviation 4.9*10^3
Stool Methanogen Levels Post-treatment	1.1*10^5 colony forming units Standard Deviation 1.3*10^5	9.4*10^7 colony forming units Standard Deviation 7.9*10^7

PRIMARY outcome

Timeframe: 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)

Outcome measures

Measure	Obese/Overweight, Prediabetic Methane Positive n=8 Participants Neomycin Rifaximin Neomycin: Neomycin: 500mg po bid for 10 days Rifaximin: Rifaximin: 550mg po tid for 10 days	Methane Non-Eradicators n=3 Participants Subjects who did not eradicate methane on breath test following antibiotic treatment
Stool Total Bacteria Levels Pre-treatment	1.1*10^9 colony forming units Standard Deviation 7.4*10^8	3.7*10^8 colony forming units Standard Deviation 6.4*10^8
Stool Total Bacteria Levels Post-treatment	1.2*10^9 colony forming units Standard Deviation 6.3*10^8	8.5*10^9 colony forming units Standard Deviation 1.4*10^10

PRIMARY outcome

Timeframe: 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)

Outcome measures

Measure	Obese/Overweight, Prediabetic Methane Positive n=8 Participants Neomycin Rifaximin Neomycin: Neomycin: 500mg po bid for 10 days Rifaximin: Rifaximin: 550mg po tid for 10 days	Methane Non-Eradicators n=3 Participants Subjects who did not eradicate methane on breath test following antibiotic treatment
Low Density Lipoprotein (LDL) Levels Before and After Antibiotic Therapy Pre-treatment	116 mg/dL Standard Deviation 42	96 mg/dL Standard Deviation 41
Low Density Lipoprotein (LDL) Levels Before and After Antibiotic Therapy Post-treatment	104 mg/dL Standard Deviation 46	111 mg/dL Standard Deviation 51

PRIMARY outcome

Timeframe: 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)

Outcome measures

Measure	Obese/Overweight, Prediabetic Methane Positive n=8 Participants Neomycin Rifaximin Neomycin: Neomycin: 500mg po bid for 10 days Rifaximin: Rifaximin: 550mg po tid for 10 days	Methane Non-Eradicators n=3 Participants Subjects who did not eradicate methane on breath test following antibiotic treatment
Total Cholesterol Levels Before and After Antibiotic Therapy Pre-treatment	192 mg/dL Standard Deviation 51	173 mg/dL Standard Deviation 41
Total Cholesterol Levels Before and After Antibiotic Therapy Post-treatment	177 mg/dL Standard Deviation 52	188 mg/dL Standard Deviation 49

PRIMARY outcome

Timeframe: 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)

Outcome measures

Measure	Obese/Overweight, Prediabetic Methane Positive n=11 Participants Neomycin Rifaximin Neomycin: Neomycin: 500mg po bid for 10 days Rifaximin: Rifaximin: 550mg po tid for 10 days	Methane Non-Eradicators n=8 Participants Subjects who did not eradicate methane on breath test following antibiotic treatment
Average Daily Caloric Loss in Stool Pre-treatment	8.1 %kcal lost Standard Deviation 2.7	8.3 %kcal lost Standard Deviation 1.8
Average Daily Caloric Loss in Stool Post-treatment	8.3 %kcal lost Standard Deviation 3.8	8.3 %kcal lost Standard Deviation 3.8

PRIMARY outcome

Timeframe: 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)

Outcome measures

Measure	Obese/Overweight, Prediabetic Methane Positive n=11 Participants Neomycin Rifaximin Neomycin: Neomycin: 500mg po bid for 10 days Rifaximin: Rifaximin: 550mg po tid for 10 days	Methane Non-Eradicators n=8 Participants Subjects who did not eradicate methane on breath test following antibiotic treatment
Gastric Emptying Pre-treatment	182.3 minutes Standard Deviation 72.8	174.9 minutes Standard Deviation 71.1
Gastric Emptying Post-treatment	163.5 minutes Standard Deviation 46.8	164.9 minutes Standard Deviation 45.8

SECONDARY outcome

Timeframe: 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)

Outcome measures

Measure	Obese/Overweight, Prediabetic Methane Positive n=11 Participants Neomycin Rifaximin Neomycin: Neomycin: 500mg po bid for 10 days Rifaximin: Rifaximin: 550mg po tid for 10 days	Methane Non-Eradicators n=8 Participants Subjects who did not eradicate methane on breath test following antibiotic treatment
Bowel Symptoms - Bloating Pre-treatment	55.09 0-100mm visual analogue scale Standard Deviation 34.18	66.8 0-100mm visual analogue scale Standard Deviation 32.4
Bowel Symptoms - Bloating Post-treatment	39.91 0-100mm visual analogue scale Standard Deviation 33.27	38.9 0-100mm visual analogue scale Standard Deviation 36.1

SECONDARY outcome

Timeframe: 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)

Outcome measures

Measure	Obese/Overweight, Prediabetic Methane Positive n=11 Participants Neomycin Rifaximin Neomycin: Neomycin: 500mg po bid for 10 days Rifaximin: Rifaximin: 550mg po tid for 10 days	Methane Non-Eradicators n=8 Participants Subjects who did not eradicate methane on breath test following antibiotic treatment
Bowel Symptoms - Abdominal Pain Pre-treatment	23.36 0-100mm visual analogue scale Standard Deviation 27.18	28.6 0-100mm visual analogue scale Standard Deviation 30.3
Bowel Symptoms - Abdominal Pain Post-treatment	18.18 0-100mm visual analogue scale Standard Deviation 29.91	21.6 0-100mm visual analogue scale Standard Deviation 34.7

SECONDARY outcome

Timeframe: 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)

Outcome measures

Measure	Obese/Overweight, Prediabetic Methane Positive n=11 Participants Neomycin Rifaximin Neomycin: Neomycin: 500mg po bid for 10 days Rifaximin: Rifaximin: 550mg po tid for 10 days	Methane Non-Eradicators n=8 Participants Subjects who did not eradicate methane on breath test following antibiotic treatment
Bowel Symptoms - Constipation Pre-treatment	30.18 0-100mm visual analogue scale Standard Deviation 29.75	31.0 0-100mm visual analogue scale Standard Deviation 30.5
Bowel Symptoms - Constipation Post-treatment	20.55 0-100mm visual analogue scale Standard Deviation 33.90	22.3 0-100mm visual analogue scale Standard Deviation 39.6

SECONDARY outcome

Timeframe: 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)

Outcome measures

Measure	Obese/Overweight, Prediabetic Methane Positive n=11 Participants Neomycin Rifaximin Neomycin: Neomycin: 500mg po bid for 10 days Rifaximin: Rifaximin: 550mg po tid for 10 days	Methane Non-Eradicators n=8 Participants Subjects who did not eradicate methane on breath test following antibiotic treatment
Bowel Symptoms - Diarrhea Pre-treatment	23.73 0-100mm visual analogue scale Standard Deviation 30.16	30.5 0-100mm visual analogue scale Standard Deviation 32.9
Bowel Symptoms - Diarrhea Post-treatment	14.64 0-100mm visual analogue scale Standard Deviation 31.01	17.3 0-100mm visual analogue scale Standard Deviation 36.0

SECONDARY outcome

Timeframe: 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)

Outcome measures

Measure	Obese/Overweight, Prediabetic Methane Positive n=11 Participants Neomycin Rifaximin Neomycin: Neomycin: 500mg po bid for 10 days Rifaximin: Rifaximin: 550mg po tid for 10 days	Methane Non-Eradicators n=8 Participants Subjects who did not eradicate methane on breath test following antibiotic treatment
Bowel Symptoms - Straining Pre-treatment	31.64 0-100mm visual analogue scale Standard Deviation 29.25	37.5 0-100mm visual analogue scale Standard Deviation 31.8
Bowel Symptoms - Straining Post-treatment	21.55 0-100mm visual analogue scale Standard Deviation 30.19	18.4 0-100mm visual analogue scale Standard Deviation 34.5

SECONDARY outcome

Timeframe: 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)

Outcome measures

Measure	Obese/Overweight, Prediabetic Methane Positive n=11 Participants Neomycin Rifaximin Neomycin: Neomycin: 500mg po bid for 10 days Rifaximin: Rifaximin: 550mg po tid for 10 days	Methane Non-Eradicators n=8 Participants Subjects who did not eradicate methane on breath test following antibiotic treatment
% Stool Dry Weight Pre-treatment	24.1 % stool dry weight Standard Deviation 5.3	25.1 % stool dry weight Standard Deviation 4.7
% Stool Dry Weight Post-treatment	22.9 % stool dry weight Standard Deviation 4.4	22.6 % stool dry weight Standard Deviation 4.4

Adverse Events

Obese/Overweight, Prediabetic Methane Positive Subjects

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Obese/Overweight, Prediabetic Methane Positive Subjects n=11 participants at risk Neomycin Rifaximin Neomycin: Neomycin: 500mg po bid for 10 days Rifaximin: Rifaximin: 550mg po tid for 10 days
Gastrointestinal disorders Loose stool	18.2% 2/11 • Number of events 2 • 20 months

Additional Information

Dr Ruchi Mathur

Cedars-Sinai Medical Center

Phone: 310-423-4774

Email: Ruchi.Mathur@cshs.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place