Insulin SensitivityPhase 2MicroB1NCT02124759

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

A Phase 2 study testing Sevelamer, Synbiotic and Maltodextrin in people with Insulin Sensitivity, run by The University of Texas Health Science Center at San Antonio at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The purpose of this study is to determine insulin sensitivity in individuals that are lean normal glucose tolerant subjects after consumption of a normal low fat diet and after a high fat diet and to explore the effects of high fat consumption on the intestinal microbiome, and metabolic endotoxemia.( Aim 1 of the… Read more about this study

Who is it for?: Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for: Insulin Sensitivity
What is being tested?: Sevelamer, Synbiotic and Maltodextrin
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 20 participants
Where: 1 siteUnited States
Study dates: 2 Apr 2014to 30 Mar 2020
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 18 to 65 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

Both genders. All races and ethnic groups.
Premenopausal women in the follicular phase, non-lactating, and with a negative pregnancy test. Postmenopausal women on stable dose of or not exposed to hormone replacement for ≥6 months.
Hematocrit (HCT)≥ 34%, serum creatinine ≤ 1.4 mg/dl, and normal serum electrolytes, urinalysis, and coagulation tests. Liver function tests (LFTs) up to 2 times normal.
Stable body weight (±2%) for ≥ 3 months
Two or less sessions of strenuous exercise/wk for last 6 months.

Who cannot join

Presence of diabetes or impaired glucose tolerance based on ADA criteria.
Current treatment with drugs known to affect glucose and lipid homeostasis. If the subject has been on a stable dose for the past 3 months, the following agents will be permitted: calcium channel blockers, β-blockers, ACE inhibitors, angiotensin receptor blockers, and statins
History of allergy to sevelamer.
History of Non-steroidal anti-inflammatory drugs or systemic steroid use for more than a week within 3 months.
Current treatment with anticoagulants (warfarin). Aspirin (up to 325 mg) and clopidogrel will be permitted if these can be held for seven days prior to the biopsy in accordance with the primary physician.
Use of agents that affect gut flora (e.g. antibiotics, colestyramine, lactulose, PEG) within 3 months.

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History of heart disease (New York Heart Classification greater than grade II; more than non-specific ST-T wave changes on the ECG), peripheral vascular disease, pulmonary disease, smokers.
Poorly controlled blood pressure (systolic BP>170, diastolic BP>95 mmHg).
Active inflammatory, autoimmune, hepatic, gastrointestinal, malignant, and psychiatric disease.
History of gastrointestinal surgery or gastrointestinal obstruction within two years.

Trial locations and contacts

1 site in 1 country.

United States1 site

Audie L. Murphy VA Hospital, STVHCS
San Antonio, Texas, 78229

Other trials in United States

About this study

Read the detailed description

We will test the hypothesis that a high fat diet given to lean, normal glucose tolerant subjects will impair insulin signaling and sensitivity and modify gut microbiome composition and enhance intestinal permeability, which will increase plasma LPS concentration, induce an inflammatory response in peripheral tissues (skeletal muscle). Also we will test the hypothesis that the inflammatory response and insulin resistance caused by high fat ingestion can be ameliorated by administering

a synbiotic (Bifidobacterium longum R0175 and oligofructose) which protects the intestinal epithelial barrier and decreases intestinal translocation of LPS; and
sevelamer, an agent which sequesters lipopolysaccharide (LPS) in the gastrointestinal tract limiting its translocation into the circulation.

All subjects are fed both a low fat diet (considered a normal diet) and high fat diet, first one and then the other in no particular sequence. After a washout period participants are fed the other type of high or low fat diet, depending on which diet they were first assigned to in order to compare the effects of the intervention on insulin sensitivity during each diet.

Conditions: Insulin Sensitivity
Being tested: Sevelamer, Synbiotic, Maltodextrin, High Fat diet, Low Fat diet
Medical subject headings: Insulin Resistance

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

SevelamerDrug
Also called Renvela
1.6 g sevelamer + 4.4 g maltodextrin three times a day
SynbioticDrug
5 g of oligofructose + 1 g Bifidobacterium longum R0175 (4 billion colony forming units (CFU)/g) three times a day.
MaltodextrinDrug
This is a control group. Maltodextrin, 6 g three times a day
High Fat dietOther
Also called Isocaloric 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.
Low Fat dietOther
Also called Isocaloric low fat (normal) diet
The isocaloric low fat diet will provide 55% energy from carbohydrates, 20% from fat and 25% from protein.

Study groups in NCT02124759
Study group	Role	What they receive
Placebo	Placebo comparator	Placebo: maltodextrin, 6 g three times a day Receives: Drug: Maltodextrin; Other: High Fat diet; Other: Low Fat diet
Sevelamer	Active comparator	Sevelamer: (1.6 g sevelamer + 4.4 g maltodextrin three times a day) Receives: Drug: Sevelamer; Other: High Fat diet; Other: Low Fat diet
Synbiotic	Active comparator	Synbiotic: 5g Oligofructose + 4x1010 Bifidobacterium longum CFU 3x daily during diet Receives: Drug: Synbiotic; Other: High Fat diet; Other: Low Fat diet

What is being measured

The primary outcome is the main question the study is designed to answer.

Insulin Sensitivity Low Fat Diet
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.
Measured: Day 28
Insulin Sensitivity High Fat Diet
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.
Measured: Day 28

Secondary outcomes (2)

Plasma Endotoxin Levels
Endotoxin is a bacterially derived product that we hypothesized would impact insulin sensitivity through pro inflammatory pathways.
Measured: At baseline, on day 3, and 28 of the intervention.
Gut Permeability
Gut permeability is measured using a lactulose/mannitol ingestion assay where urine samples are collected to analyse the ratio of excreted lactulose:mannitol.
Measured: on Day 24 of the intervention.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

2 Apr 201430 Mar 2020

First posted28 Apr 2014 (estimated)
Study start2 Apr 2014
Primary completion23 Feb 2018
Study completion30 Mar 2020

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.
Other trials for Insulin SensitivityStudies of the same condition, open and under way.
More trials run by The University of Texas Health Science Center at San AntonioThe 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: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 20 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02124759
Sponsor's protocol ID: HSC20130459H
Other IDs: IRB #20130458H
Acronym: MicroB1
Status last verified: Sep 2021
First submitted: 24 Apr 2014
Last updated: 15 Oct 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruiting
Effect of Probiotics on Insulin Sensitivity in Overweight and Obese Pregnancy
Obesity & Overweight, Gestational Diabetes Mellitus (GDM)
Not yet recruitingPhase 2
Trial of the Combination of Alpha-Lipoic Acid and Mirabegron in Women and in Men With Obesity
Insulin Resistance, Obesity
Recruiting
Improving Sleep Health and Circadian Timing to Support Cardiometabolic Health in Adolescents
Overweight Adolescents, Sleep
Not yet recruitingObservational study
Clinical Research Trial to Study Insulin Sensitivity Using Automated Glucose Clamp Technology
Obesity Type 2 Diabetes Mellitus, Obese Adults
Not yet recruiting
Effects of Mango on Insulin Sensitivity in Prediabetes
Pre Diabetes

All Insulin Sensitivity trials

Study at a glance

From the registry record, last updated by the sponsor on 15 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Mechanism of Microbiome-induced Insulin Resistance in Humans (Aim 1)
ClinicalTrials.gov ID: NCT02124759
Acronym / sponsor ID: MicroB1 / HSC20130459H
Conditions: Insulin Sensitivity
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 20 participants (actual)
Lead sponsor: The University of Texas Health Science Center at San AntonioUniversity, hospital or other
Collaborators: American Diabetes Association
Study start: 2 Apr 2014 (actual)
Primary completion: 23 Feb 2018 (actual)
Study completion: 30 Mar 2020 (actual)
First posted: 28 Apr 2014 (estimated)
Results: Posted 15 Oct 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

a synbiotic (Bifidobacterium longum R0175 and oligofructose) which protects the intestinal epithelial barrier and decreases intestinal translocation of LPS; and
sevelamer, an agent which sequesters lipopolysaccharide (LPS) in the gastrointestinal tract limiting its translocation into the circulation.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 3

Arm	Type	Receives
Placebo	Placebo comparator	Drug: Maltodextrin, Other: High Fat diet, Other: Low Fat dietPlacebo: maltodextrin, 6 g three times a day
Sevelamer	Active comparator	Drug: Sevelamer, Other: High Fat diet, Other: Low Fat dietSevelamer: (1.6 g sevelamer + 4.4 g maltodextrin three times a day)
Synbiotic	Active comparator	Drug: Synbiotic, Other: High Fat diet, Other: Low Fat dietSynbiotic: 5g Oligofructose + 4x1010 Bifidobacterium longum CFU 3x daily during diet

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Both genders. All races and ethnic groups.
Premenopausal women in the follicular phase, non-lactating, and with a negative pregnancy test. Postmenopausal women on stable dose of or not exposed to hormone replacement for ≥6 months.
Hematocrit (HCT)≥ 34%, serum creatinine ≤ 1.4 mg/dl, and normal serum electrolytes, urinalysis, and coagulation tests. Liver function tests (LFTs) up to 2 times normal.
Stable body weight (±2%) for ≥ 3 months
Two or less sessions of strenuous exercise/wk for last 6 months.

Key exclusion criteria (10 listed)

Presence of diabetes or impaired glucose tolerance based on ADA criteria.
Current treatment with drugs known to affect glucose and lipid homeostasis. If the subject has been on a stable dose for the past 3 months, the following agents will be permitted: calcium channel blockers, β-blockers, ACE inhibitors, angiotensin receptor blockers, and statins
History of allergy to sevelamer.
History of Non-steroidal anti-inflammatory drugs or systemic steroid use for more than a week within 3 months.
Current treatment with anticoagulants (warfarin). Aspirin (up to 325 mg) and clopidogrel will be permitted if these can be held for seven days prior to the biopsy in accordance with the primary physician.

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
SevelamerAlso: Renvela1.6 g sevelamer + 4.4 g maltodextrin three times a day	Drug	Sevelamer
Synbiotic5 g of oligofructose + 1 g Bifidobacterium longum R0175 (4 billion colony forming units (CFU)/g) three times a day.	Drug	Synbiotic
MaltodextrinThis is a control group. Maltodextrin, 6 g three times a day	Drug	Placebo
High Fat dietAlso: Isocaloric high fat dietThe 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.	Other	Placebo, Sevelamer, Synbiotic
Low Fat dietAlso: Isocaloric low fat (normal) dietThe isocaloric low fat diet will provide 55% energy from carbohydrates, 20% from fat and 25% from protein.	Other	Placebo, Sevelamer, Synbiotic

Primary outcome

Insulin Sensitivity Low Fat Diet
Time frame: Day 28
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.
Insulin Sensitivity High Fat Diet
Time frame: 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.

2 secondary outcomes

Plasma Endotoxin Levels
Time frame: At baseline, on day 3, and 28 of the intervention.
Gut Permeability
Time frame: on Day 24 of the intervention.

Results and safety

Results posted to the registry on 15 Oct 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo	6	1
Sevelamer	7	4
Synbiotic	7	3

Primary outcome: Insulin Sensitivity Low Fat Diet

Time frame: Day 28. Mean (Standard Deviation). Unit: M value (mg/kg/min

Measure	Placebo n = 1	Sevelamer n = 4	Synbiotic n = 3
Value	6.5 (0)	8.2 (2.4)	9.8 (0.6)

Primary outcome: Insulin Sensitivity High Fat Diet

Time frame: Day 28. Mean (Standard Deviation). Unit: M Value (mg/kg/min)

Measure	Placebo n = 1	Sevelamer n = 4	Synbiotic n = 3
Value	6.8 (0)	8.5 (1.87)	8.8 (1.63)

Placebo vs Sevelamer vs Synbiotic: p >0.05, t-test, 2 sided

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: 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.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	0 of 6 (0%)	3 of 6 (50%)	0 of 6
Sevelamer	0 of 7 (0%)	3 of 7 (42.9%)	0 of 7
Synbiotic	0 of 7 (0%)	4 of 7 (57.1%)	0 of 7

Limitations and caveats (from the sponsor): Despite continued recruitment efforts, we had difficulty with subjects fully completing the study due to dissatisfaction with the diets. Evaluable subjects completed both low and high fat diet while randomized to one of the three interventions, and only insulin sensitivity was captured for both the low fat and high fat diets due to the low completion numbers.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Insulin Sensitivity

Active, not recruiting
Effect of Probiotics on Insulin Sensitivity in Overweight and Obese Pregnancy
Obesity & Overweight, Gestational Diabetes Mellitus (GDM)
Not yet recruitingPhase 2
Trial of the Combination of Alpha-Lipoic Acid and Mirabegron in Women and in Men With Obesity
Insulin Resistance, Obesity
Recruiting
Improving Sleep Health and Circadian Timing to Support Cardiometabolic Health in Adolescents
Overweight Adolescents, Sleep
Not yet recruitingObservational study
Clinical Research Trial to Study Insulin Sensitivity Using Automated Glucose Clamp Technology
Obesity Type 2 Diabetes Mellitus, Obese Adults
Not yet recruiting
Effects of Mango on Insulin Sensitivity in Prediabetes
Pre Diabetes

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.

Nicolas Musi, MD. principal investigator

The University of Texas Health Science Center at San Antonio

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 Sevelamer, Synbiotic and Maltodextrin in people with Insulin Sensitivity, run by The University of Texas Health Science Center at San Antonio 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 10 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 15 Oct 2021. 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. Some participants in this study may receive a placebo. 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 15 Oct 2021). 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?

Insulin Sensitivity Low Fat Diet (time frame: Day 28). The study lists 2 primary outcomes in all. 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 NCT02124759.

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 15 Oct 2021.