Trial Outcomes & Findings for Mechanism of Microbiome-induced Insulin Resistance in Humans (Aim 1) (NCT NCT02124759)

Last Updated: 2021-10-15

Results Overview

Skeletal muscle insulin sensitivity measured after 28 days of low fat diet and drug intervention. The isocaloric low fat diet will provide 55% energy from carbohydrates, 20% from fat and 25% from protein.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

20 participants

Primary outcome timeframe

Day 28

Results posted on

2021-10-15

Participant Flow

Subjects were initially screened by BMI and glucose tolerance via OGTT. Qualified Study participants were then assigned to begin a low or high isocaloric diet and then randomized to one of the 3 arms for 4 weeks. After a 10-12 week washout, subjects are changed over to the other diet and remain in the same arm of the study that they were in previously.

Participant milestones

Participant milestones
Measure	Placebo placebo, maltodextrin, 6 g three times a day during diet This is a control group.	Sevelamer Sevelamer: 1.6 g sevelamer + 4.4 g maltodextrin three times a day during diet	Synbiotic 5g Oligofructose + 4x1010 Bifidobacterium longum CFU 3x daily during diet
Overall Study STARTED	6	7	7
Overall Study Subjects Randomized to Intervention	4	5	4
Overall Study Low Fat Diet	4	4	4
Overall Study High Fat Diet	2	5	4
Overall Study COMPLETED	1	4	3
Overall Study NOT COMPLETED	5	3	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo placebo, maltodextrin, 6 g three times a day during diet This is a control group.	Sevelamer Sevelamer: 1.6 g sevelamer + 4.4 g maltodextrin three times a day during diet	Synbiotic 5g Oligofructose + 4x1010 Bifidobacterium longum CFU 3x daily during diet
Overall Study Withdrawal by Subject	3	1	1
Overall Study Screen Fail	2	2	3

Baseline Characteristics

Mechanism of Microbiome-induced Insulin Resistance in Humans (Aim 1)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=1 Participants placebo, maltodextrin, 6 g three times a day	Sevelamer n=4 Participants Sevelamer: 1.6 g sevelamer + 4.4 g maltodextrin three times a day	Synbiotic n=3 Participants \*synbiotic \[5 g of oligofructose + 1 g Bifidobacterium longum R0175 (4 billion CFU/g)three times a day\]	Total n=8 Participants Total of all reporting groups
Age, Continuous	62 years STANDARD_DEVIATION 0 • n=5 Participants	40.5 years STANDARD_DEVIATION 22.0 • n=7 Participants	59 years STANDARD_DEVIATION 3.8 • n=5 Participants	50.6 years STANDARD_DEVIATION 18.1 • n=4 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	7 Participants n=4 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants
Region of Enrollment United States	1 participants n=5 Participants	4 participants n=7 Participants	3 participants n=5 Participants	8 participants n=4 Participants

PRIMARY outcome

Timeframe: Day 28

Outcome measures

Outcome measures
Measure	Sevelamer n=4 Participants The high fat diet will provide 60% of energy from fat (of which 50% from saturated fat), 15% of energy as CHO and 25% from protein. subjects will be randomized to receive, in a double-blind fashion Sevelamer: 1.6 g sevelamer + 4.4 g maltodextrin three times a day	Synbiotic n=3 Participants The high fat diet will provide 60% of energy from fat (of which 50% from saturated fat), 15% of energy as CHO and 25% from protein. subjects will be randomized to receive, in a double-blind fashion Synbiotic: 5 g of oligofructose + 1 g Bifidobacterium longum R0175 (4 billion colony forming units (CFU)/g) three times a day.	Placebo n=1 Participants placebo, maltodextrin, 6 g three times a day
Insulin Sensitivity Low Fat Diet	8.2 M value (mg/kg/min Standard Deviation 2.4	9.8 M value (mg/kg/min Standard Deviation 0.6	6.5 M value (mg/kg/min Standard Deviation 0

PRIMARY outcome

Timeframe: Day 28

Skeletal muscle insulin sensitivity measured after 28 days of high fat diet. The High Fat diet consists of 60% energy from fat (50% saturated), 15% of energy as carbohydrate and 25% from protein consumed while study intervention is being administered.

Outcome measures

Outcome measures
Measure	Sevelamer n=4 Participants The high fat diet will provide 60% of energy from fat (of which 50% from saturated fat), 15% of energy as CHO and 25% from protein. subjects will be randomized to receive, in a double-blind fashion Sevelamer: 1.6 g sevelamer + 4.4 g maltodextrin three times a day	Synbiotic n=3 Participants The high fat diet will provide 60% of energy from fat (of which 50% from saturated fat), 15% of energy as CHO and 25% from protein. subjects will be randomized to receive, in a double-blind fashion Synbiotic: 5 g of oligofructose + 1 g Bifidobacterium longum R0175 (4 billion colony forming units (CFU)/g) three times a day.	Placebo n=1 Participants placebo, maltodextrin, 6 g three times a day
Insulin Sensitivity High Fat Diet	8.5 M Value (mg/kg/min) Standard Deviation 1.87	8.8 M Value (mg/kg/min) Standard Deviation 1.63	6.8 M Value (mg/kg/min) Standard Deviation 0

SECONDARY outcome

Timeframe: At baseline, on day 3, and 28 of the intervention.

Population: Plasma Endotoxin levels not analyzed after study completed enrollment due to low subject enrollment and limited ability to compare between subjects (max n=3 per group)

Endotoxin is a bacterially derived product that we hypothesized would impact insulin sensitivity through pro inflammatory pathways.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: on Day 24 of the intervention.

Population: Gut permeability not analyzed after study completed enrollment due to low subject enrollment and limited ability to compare between subjects (max n=3 per group)

Gut permeability is measured using a lactulose/mannitol ingestion assay where urine samples are collected to analyse the ratio of excreted lactulose:mannitol.

Outcome measures

Outcome data not reported

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Sevelamer

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Synbiotic

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Placebo n=6 participants at risk Maltodextrin: This is a control group that were fed both low and high fat diets. Maltodextrin, 6 g three times a day	Sevelamer n=7 participants at risk Sevelamer: 1.6 g sevelamer + 4.4 g maltodextrin three times a day that were fed either a low fat or high fat diet, followed by the other type of diet.	Synbiotic n=7 participants at risk Synbiotic: 5 g of oligofructose + 1 g Bifidobacterium longum R0175 (4 billion colony forming units (CFU)/g) three times a day that were fed either a low fat or high fat diet, followed by the other type of diet.
Gastrointestinal disorders Nausea	16.7% 1/6 • Number of events 1 • Adverse Event Data was collected over the course of the study intervention period, beginning with subject's enrollment into study and ending once they completed all visits. This period takes approximately 6 months from screening to completion of all visits. Adverse events were collected per arm of the study, for placebo, sevelamer and synbiotic, rather than by arm and low or high fat diet. Each arm reports adverse events to include the participant assignment to either low or high fat diets.	14.3% 1/7 • Number of events 1 • Adverse Event Data was collected over the course of the study intervention period, beginning with subject's enrollment into study and ending once they completed all visits. This period takes approximately 6 months from screening to completion of all visits. Adverse events were collected per arm of the study, for placebo, sevelamer and synbiotic, rather than by arm and low or high fat diet. Each arm reports adverse events to include the participant assignment to either low or high fat diets.	0.00% 0/7 • Adverse Event Data was collected over the course of the study intervention period, beginning with subject's enrollment into study and ending once they completed all visits. This period takes approximately 6 months from screening to completion of all visits. Adverse events were collected per arm of the study, for placebo, sevelamer and synbiotic, rather than by arm and low or high fat diet. Each arm reports adverse events to include the participant assignment to either low or high fat diets.
Gastrointestinal disorders Diarrhea	16.7% 1/6 • Number of events 3 • Adverse Event Data was collected over the course of the study intervention period, beginning with subject's enrollment into study and ending once they completed all visits. This period takes approximately 6 months from screening to completion of all visits. Adverse events were collected per arm of the study, for placebo, sevelamer and synbiotic, rather than by arm and low or high fat diet. Each arm reports adverse events to include the participant assignment to either low or high fat diets.	0.00% 0/7 • Adverse Event Data was collected over the course of the study intervention period, beginning with subject's enrollment into study and ending once they completed all visits. This period takes approximately 6 months from screening to completion of all visits. Adverse events were collected per arm of the study, for placebo, sevelamer and synbiotic, rather than by arm and low or high fat diet. Each arm reports adverse events to include the participant assignment to either low or high fat diets.	0.00% 0/7 • Adverse Event Data was collected over the course of the study intervention period, beginning with subject's enrollment into study and ending once they completed all visits. This period takes approximately 6 months from screening to completion of all visits. Adverse events were collected per arm of the study, for placebo, sevelamer and synbiotic, rather than by arm and low or high fat diet. Each arm reports adverse events to include the participant assignment to either low or high fat diets.
Nervous system disorders Headache	16.7% 1/6 • Number of events 1 • Adverse Event Data was collected over the course of the study intervention period, beginning with subject's enrollment into study and ending once they completed all visits. This period takes approximately 6 months from screening to completion of all visits. Adverse events were collected per arm of the study, for placebo, sevelamer and synbiotic, rather than by arm and low or high fat diet. Each arm reports adverse events to include the participant assignment to either low or high fat diets.	0.00% 0/7 • Adverse Event Data was collected over the course of the study intervention period, beginning with subject's enrollment into study and ending once they completed all visits. This period takes approximately 6 months from screening to completion of all visits. Adverse events were collected per arm of the study, for placebo, sevelamer and synbiotic, rather than by arm and low or high fat diet. Each arm reports adverse events to include the participant assignment to either low or high fat diets.	0.00% 0/7 • Adverse Event Data was collected over the course of the study intervention period, beginning with subject's enrollment into study and ending once they completed all visits. This period takes approximately 6 months from screening to completion of all visits. Adverse events were collected per arm of the study, for placebo, sevelamer and synbiotic, rather than by arm and low or high fat diet. Each arm reports adverse events to include the participant assignment to either low or high fat diets.
Surgical and medical procedures Hematoma	0.00% 0/6 • Adverse Event Data was collected over the course of the study intervention period, beginning with subject's enrollment into study and ending once they completed all visits. This period takes approximately 6 months from screening to completion of all visits. Adverse events were collected per arm of the study, for placebo, sevelamer and synbiotic, rather than by arm and low or high fat diet. Each arm reports adverse events to include the participant assignment to either low or high fat diets.	0.00% 0/7 • Adverse Event Data was collected over the course of the study intervention period, beginning with subject's enrollment into study and ending once they completed all visits. This period takes approximately 6 months from screening to completion of all visits. Adverse events were collected per arm of the study, for placebo, sevelamer and synbiotic, rather than by arm and low or high fat diet. Each arm reports adverse events to include the participant assignment to either low or high fat diets.	14.3% 1/7 • Number of events 1 • Adverse Event Data was collected over the course of the study intervention period, beginning with subject's enrollment into study and ending once they completed all visits. This period takes approximately 6 months from screening to completion of all visits. Adverse events were collected per arm of the study, for placebo, sevelamer and synbiotic, rather than by arm and low or high fat diet. Each arm reports adverse events to include the participant assignment to either low or high fat diets.
Gastrointestinal disorders Mouth Ulcers	16.7% 1/6 • Number of events 1 • Adverse Event Data was collected over the course of the study intervention period, beginning with subject's enrollment into study and ending once they completed all visits. This period takes approximately 6 months from screening to completion of all visits. Adverse events were collected per arm of the study, for placebo, sevelamer and synbiotic, rather than by arm and low or high fat diet. Each arm reports adverse events to include the participant assignment to either low or high fat diets.	14.3% 1/7 • Number of events 1 • Adverse Event Data was collected over the course of the study intervention period, beginning with subject's enrollment into study and ending once they completed all visits. This period takes approximately 6 months from screening to completion of all visits. Adverse events were collected per arm of the study, for placebo, sevelamer and synbiotic, rather than by arm and low or high fat diet. Each arm reports adverse events to include the participant assignment to either low or high fat diets.	0.00% 0/7 • Adverse Event Data was collected over the course of the study intervention period, beginning with subject's enrollment into study and ending once they completed all visits. This period takes approximately 6 months from screening to completion of all visits. Adverse events were collected per arm of the study, for placebo, sevelamer and synbiotic, rather than by arm and low or high fat diet. Each arm reports adverse events to include the participant assignment to either low or high fat diets.
Ear and labyrinth disorders Ear Itching	16.7% 1/6 • Number of events 1 • Adverse Event Data was collected over the course of the study intervention period, beginning with subject's enrollment into study and ending once they completed all visits. This period takes approximately 6 months from screening to completion of all visits. Adverse events were collected per arm of the study, for placebo, sevelamer and synbiotic, rather than by arm and low or high fat diet. Each arm reports adverse events to include the participant assignment to either low or high fat diets.	0.00% 0/7 • Adverse Event Data was collected over the course of the study intervention period, beginning with subject's enrollment into study and ending once they completed all visits. This period takes approximately 6 months from screening to completion of all visits. Adverse events were collected per arm of the study, for placebo, sevelamer and synbiotic, rather than by arm and low or high fat diet. Each arm reports adverse events to include the participant assignment to either low or high fat diets.	0.00% 0/7 • Adverse Event Data was collected over the course of the study intervention period, beginning with subject's enrollment into study and ending once they completed all visits. This period takes approximately 6 months from screening to completion of all visits. Adverse events were collected per arm of the study, for placebo, sevelamer and synbiotic, rather than by arm and low or high fat diet. Each arm reports adverse events to include the participant assignment to either low or high fat diets.
Gastrointestinal disorders Abdominal Bloating/Flatulence	0.00% 0/6 • Adverse Event Data was collected over the course of the study intervention period, beginning with subject's enrollment into study and ending once they completed all visits. This period takes approximately 6 months from screening to completion of all visits. Adverse events were collected per arm of the study, for placebo, sevelamer and synbiotic, rather than by arm and low or high fat diet. Each arm reports adverse events to include the participant assignment to either low or high fat diets.	14.3% 1/7 • Number of events 1 • Adverse Event Data was collected over the course of the study intervention period, beginning with subject's enrollment into study and ending once they completed all visits. This period takes approximately 6 months from screening to completion of all visits. Adverse events were collected per arm of the study, for placebo, sevelamer and synbiotic, rather than by arm and low or high fat diet. Each arm reports adverse events to include the participant assignment to either low or high fat diets.	14.3% 1/7 • Number of events 2 • Adverse Event Data was collected over the course of the study intervention period, beginning with subject's enrollment into study and ending once they completed all visits. This period takes approximately 6 months from screening to completion of all visits. Adverse events were collected per arm of the study, for placebo, sevelamer and synbiotic, rather than by arm and low or high fat diet. Each arm reports adverse events to include the participant assignment to either low or high fat diets.
Vascular disorders Hypertension	0.00% 0/6 • Adverse Event Data was collected over the course of the study intervention period, beginning with subject's enrollment into study and ending once they completed all visits. This period takes approximately 6 months from screening to completion of all visits. Adverse events were collected per arm of the study, for placebo, sevelamer and synbiotic, rather than by arm and low or high fat diet. Each arm reports adverse events to include the participant assignment to either low or high fat diets.	0.00% 0/7 • Adverse Event Data was collected over the course of the study intervention period, beginning with subject's enrollment into study and ending once they completed all visits. This period takes approximately 6 months from screening to completion of all visits. Adverse events were collected per arm of the study, for placebo, sevelamer and synbiotic, rather than by arm and low or high fat diet. Each arm reports adverse events to include the participant assignment to either low or high fat diets.	14.3% 1/7 • Number of events 1 • Adverse Event Data was collected over the course of the study intervention period, beginning with subject's enrollment into study and ending once they completed all visits. This period takes approximately 6 months from screening to completion of all visits. Adverse events were collected per arm of the study, for placebo, sevelamer and synbiotic, rather than by arm and low or high fat diet. Each arm reports adverse events to include the participant assignment to either low or high fat diets.
Surgical and medical procedures Vasovagal Syncope	0.00% 0/6 • Adverse Event Data was collected over the course of the study intervention period, beginning with subject's enrollment into study and ending once they completed all visits. This period takes approximately 6 months from screening to completion of all visits. Adverse events were collected per arm of the study, for placebo, sevelamer and synbiotic, rather than by arm and low or high fat diet. Each arm reports adverse events to include the participant assignment to either low or high fat diets.	14.3% 1/7 • Number of events 1 • Adverse Event Data was collected over the course of the study intervention period, beginning with subject's enrollment into study and ending once they completed all visits. This period takes approximately 6 months from screening to completion of all visits. Adverse events were collected per arm of the study, for placebo, sevelamer and synbiotic, rather than by arm and low or high fat diet. Each arm reports adverse events to include the participant assignment to either low or high fat diets.	0.00% 0/7 • Adverse Event Data was collected over the course of the study intervention period, beginning with subject's enrollment into study and ending once they completed all visits. This period takes approximately 6 months from screening to completion of all visits. Adverse events were collected per arm of the study, for placebo, sevelamer and synbiotic, rather than by arm and low or high fat diet. Each arm reports adverse events to include the participant assignment to either low or high fat diets.
General disorders Dehydration	16.7% 1/6 • Number of events 1 • Adverse Event Data was collected over the course of the study intervention period, beginning with subject's enrollment into study and ending once they completed all visits. This period takes approximately 6 months from screening to completion of all visits. Adverse events were collected per arm of the study, for placebo, sevelamer and synbiotic, rather than by arm and low or high fat diet. Each arm reports adverse events to include the participant assignment to either low or high fat diets.	0.00% 0/7 • Adverse Event Data was collected over the course of the study intervention period, beginning with subject's enrollment into study and ending once they completed all visits. This period takes approximately 6 months from screening to completion of all visits. Adverse events were collected per arm of the study, for placebo, sevelamer and synbiotic, rather than by arm and low or high fat diet. Each arm reports adverse events to include the participant assignment to either low or high fat diets.	0.00% 0/7 • Adverse Event Data was collected over the course of the study intervention period, beginning with subject's enrollment into study and ending once they completed all visits. This period takes approximately 6 months from screening to completion of all visits. Adverse events were collected per arm of the study, for placebo, sevelamer and synbiotic, rather than by arm and low or high fat diet. Each arm reports adverse events to include the participant assignment to either low or high fat diets.
Gastrointestinal disorders Gum Infection	0.00% 0/6 • Adverse Event Data was collected over the course of the study intervention period, beginning with subject's enrollment into study and ending once they completed all visits. This period takes approximately 6 months from screening to completion of all visits. Adverse events were collected per arm of the study, for placebo, sevelamer and synbiotic, rather than by arm and low or high fat diet. Each arm reports adverse events to include the participant assignment to either low or high fat diets.	0.00% 0/7 • Adverse Event Data was collected over the course of the study intervention period, beginning with subject's enrollment into study and ending once they completed all visits. This period takes approximately 6 months from screening to completion of all visits. Adverse events were collected per arm of the study, for placebo, sevelamer and synbiotic, rather than by arm and low or high fat diet. Each arm reports adverse events to include the participant assignment to either low or high fat diets.	14.3% 1/7 • Number of events 1 • Adverse Event Data was collected over the course of the study intervention period, beginning with subject's enrollment into study and ending once they completed all visits. This period takes approximately 6 months from screening to completion of all visits. Adverse events were collected per arm of the study, for placebo, sevelamer and synbiotic, rather than by arm and low or high fat diet. Each arm reports adverse events to include the participant assignment to either low or high fat diets.

Additional Information

Dr. Nicolas Musi

UTHSC San Antonio

Phone: 630-5001

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place