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| Name | Class |
|---|---|
| American Diabetes Association | OTHER |
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The purpose of this study is to determine whether microbiome modulation and an experimental reduction in plasma LPS concentration improve inflammation and insulin action in insulin resistant (obese and T2DM) subjects.
In this Aim we will test the hypothesis that lowering lipopolysaccharide (LPS) concentration in the circulation will improve systemic (muscle) inflammation and glucose metabolism in insulin resistant (obese and T2DM) subjects by protecting the intestinal barrier with a synbiotic (Bifidobacterium longum R0175 and oligofructose) or by sequestering LPS in the gastrointestinal lumen with sevelamer.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Type2 Diabetes Mellitus - Placebo | Placebo Comparator | Type 2 Diabetes Mellitus subjects will receive maltodextrin (placebo) |
|
| Obese with NGT - Placebo | Placebo Comparator | Obese (BMI = 30-37 kg/m2) normal glucose tolerant (NGT) subjects will receive maltodextrin (placebo) |
|
| Lean with NGT -Placebo | Placebo Comparator | Lean (BMI< 26 kg/m2) normal glucose tolerant (NGT) will receive maltodextrin (placebo) |
|
| Type2 Diabetes Mellitus - Synbiotic | Active Comparator | Type 2 Diabetic subjects will receive synbiotic |
|
| Type2 Diabetes Mellitus - Sevelamer | Active Comparator | Type 2 Diabetic subjects will receive sevelamer |
|
| Obese with NGT - Synbiotic | Active Comparator |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Maltodextrin | Drug | Maltodextrin treatment as a placebo group. Maltodextrin, 6 gm three times a day for 4 weeks. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Insulin Sensitivity | Insulin sensitivity in skeletal muscle (M value) as measured by hyperinsulinemic euglycemic clamp study. The clamp study tests the ability of peripheral tissues such as skeletal muscle to uptake glucose in response to a constant insulin stimulus, which give a measure of sensitivity to insulin action. 60 mU/m2*min insulin was infused into subjects for 180 minutes with concomitant adjustment of glucose infusion rate using D20 glucose to maintain a clamped plasma glucose concentration of 100 mg/dL. When the glucose infusion rate equals the rate of glucose uptake and the targeted glucose concentration is achieved, the clamp is at steady-state equilibrium. Steady-state glucose infusion rate at 150min-180mins was used as the measure to calculate the M value. | Change from baseline insulin sensitivity at 28 days of the intervention. |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma Endotoxin Level and Its Panel. | Plasma Lipopolysaccharide (LPS) after intervention period | Change from baseline plasma endotoxin level and its panel during 28 days. |
| Gut Permeability | urine lactulose: mannitol ratio. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Nicolas Musi, MD. | The University of Texas Health Science Center at San Antonio | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Audie L. Murphy VA Hospital, STVHCS | San Antonio | Texas | 78229 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 42141362 | Derived | Baeuerle E, Semwal MK, Nie J, Zhang N, Liang H, Ganapathy V, Sathavarodom N, Fernandez R, Wang CP, Espinoza S, Dong Q, Gao X, Yang Z, Kostic A, Musi N. Effect of Sevelamer and B. longum on Insulin Sensitivity in Participants With Obesity: A Randomized Clinical Trial. Obesity (Silver Spring). 2026 May 15. doi: 10.1002/oby.70224. Online ahead of print. |
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69 participants were screened, 8 were screen failures, so not randomized.
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| ID | Title | Description |
|---|---|---|
| FG000 | Lean With NGT-Placebo | Lean (BMI< 26 kg/m2) normal glucose tolerant Maltodextrin treatment as a placebo group. Maltodextrin, 6 gm three times a day for 4 weeks. |
| FG001 | Lean With NGT-Sevelamer | Lean (BMI< 26 kg/m2) normal glucose tolerant Sevelamer (1.6 g sevelamer + 4.4 g maltodextrin three times a day), for 4 weeks |
| FG002 | Lean With NGT-Synbiotic | Lean (BMI< 26 kg/m2) normal glucose tolerant Synbiotic [5 g of oligofructose + 1 g Bifidobacterium longum R0175 (4 billion colony forming unit (CFU)/g) three times a day) for 4 weeks.](streamdown:incomplete-link) |
| FG003 | Obese With NGT-Placebo | Obese (BMI = 30-37 kg/m2) normal glucose tolerant. Maltodextrin treatment as a placebo group. Maltodextrin, 6 gm three times a day for 4 weeks |
| FG004 | Obese With NGT-Sevelamer | Obese (BMI = 30-37 kg/m2) normal glucose tolerant. Sevelamer (1.6 g sevelamer + 4.4 g maltodextrin three times a day), for 4 weeks |
| FG005 | Obese With NGT-Synbiotic | Obese (BMI = 30-37 kg/m2) normal glucose tolerant. Synbiotic [5 g of oligofructose + 1 g Bifidobacterium longum R0175 (4 billion colony forming unit (CFU)/g) three times a day) for 4 weeks.](streamdown:incomplete-link) |
| FG006 | Type 2 Diabetes -Placebo | Type 2 Diabetics Maltodextrin treatment as a placebo group. Maltodextrin, 6 gm three times a day for 4 weeks. |
| FG007 | Type 2 Diabetes-Sevelamer | Type 2 Diabetics Sevelamer (1.6 g sevelamer + 4.4 g maltodextrin three times a day), for 4 weeks |
| FG008 | Type 2 Diabetes-Synbiotic | Type 2 Diabetics Synbiotic [5 g of oligofructose + 1 g Bifidobacterium longum R0175 (4 billion colony forming unit (CFU)/g) three times a day) for 4 weeks.](streamdown:incomplete-link) |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Low enrollment of Type 2 Diabetics in this study due to exclusionary medication criteria including many common diabetes medications such as metformin which interfere with microbiome content. Subjects were randomized to treatment and no diabetic subjects ended up in the sevelamer treatment group.
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| ID | Title | Description |
|---|---|---|
| BG000 | Lean With NGT-Placebo | Lean (BMI< 26 kg/m2) normal glucose tolerant Maltodextrin treatment as a placebo group. Maltodextrin, 6 gm three times a day for 4 weeks. |
| BG001 | Lean With NGT-Sevelamer |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Insulin Sensitivity | Insulin sensitivity in skeletal muscle (M value) as measured by hyperinsulinemic euglycemic clamp study. The clamp study tests the ability of peripheral tissues such as skeletal muscle to uptake glucose in response to a constant insulin stimulus, which give a measure of sensitivity to insulin action. 60 mU/m2*min insulin was infused into subjects for 180 minutes with concomitant adjustment of glucose infusion rate using D20 glucose to maintain a clamped plasma glucose concentration of 100 mg/dL. When the glucose infusion rate equals the rate of glucose uptake and the targeted glucose concentration is achieved, the clamp is at steady-state equilibrium. Steady-state glucose infusion rate at 150min-180mins was used as the measure to calculate the M value. | Enrollment and completion for Type 2 diabetes mellitus group was low due to exclusionary criteria that prevented most diabetes medications from being used while in the study. Lean with NGT and Obese with NGT groups completed 6 control, 8 sevelamer, 8 synbiotic subjects for Lean group and 10 control, 9 sevelamer and 9 synbiotic for Obese group. | Posted | Mean | Standard Deviation | M Value (mg/kg/min) | Change from baseline insulin sensitivity at 28 days of the intervention. |
Study participants were enrolled in the study for approximately 2-3 months.
Adverse Event data was collected over the course of the subject's participation in the study, often at followup visits as part of biopsy site checks.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Lean With NGT-Placebo | Lean (BMI< 26 kg/m2) normal glucose tolerant Maltodextrin treatment as a placebo group. Maltodextrin, 6 gm three times a day for 4 weeks |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Biopsy Site Pain/soreness | Surgical and medical procedures | Non-systematic Assessment | Biopsies of the vastus lateralis are obtained under local anesthesia at visit 4 and 6, before and after insulin clamp. All events expected given procedure protocol. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Nicolas Musi | San Antonio Geriatric Research, Education, and Clinical Center | (210) 562-6140 | musi@uthscsa.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Mar 12, 2019 | Nov 13, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D007333 | Insulin Resistance |
| ID | Term |
|---|---|
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| C008315 | maltodextrin |
| D058616 | Synbiotics |
| D000069603 | Sevelamer |
| ID | Term |
|---|---|
| D056692 | Prebiotics |
| D019587 | Dietary Supplements |
| D005502 | Food |
| D000066888 | Diet, Food, and Nutrition |
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Obese (BMI = 30-37 kg/m2) normal glucose tolerant subjects (NGT) will receive Synbiotic
|
| Obese with NGT - Sevelamer | Active Comparator | Obese subjects (BMI = 30-37 kg/m2) normal glucose tolerant (NGT) will receive Sevelamer |
|
| Lean with NGT - Synbiotic | Active Comparator | Lean (BMI< 26 kg/m2) normal glucose tolerant (NGT) will receive Synbiotic |
|
| Lean with NGT - Sevelamer | Active Comparator | Lean (BMI< 26 kg/m2) normal glucose tolerant (NGT) will receive Sevelamer |
|
| Synbiotic | Drug | Synbiotic [5 g of oligofructose + 1 g Bifidobacterium longum R0175 (4 billion colony forming unit (CFU)/g) three times a day) for 4 weeks.](streamdown:incomplete-link) |
|
| Sevelamer | Drug | Sevelamer (1.6 g sevelamer + 4.4 g maltodextrin three times a day), for 4 weeks |
|
|
| Change from baseline gut permeability at 24 days of the intervention. |
| Withdrawal by Subject |
|
| Physician Decision |
|
Lean (BMI< 26 kg/m2) normal glucose tolerant Sevelamer (1.6 g sevelamer + 4.4 g maltodextrin three times a day), for 4 weeks
| BG002 | Lean With NGT-Synbiotic | Lean (BMI< 26 kg/m2) normal glucose tolerant Synbiotic [5 g of oligofructose + 1 g Bifidobacterium longum R0175 (4 billion colony forming unit (CFU)/g) three times a day) for 4 weeks.](streamdown:incomplete-link) |
| BG003 | Obese With NGT-Placebo | Obese (BMI = 30-37 kg/m2) normal glucose tolerant. Maltodextrin treatment as a placebo group. Maltodextrin, 6 gm three times a day for 4 weeks. |
| BG004 | Obese With NGT-Sevelamer | Obese (BMI = 30-37 kg/m2) normal glucose tolerant. Sevelamer (1.6 g sevelamer + 4.4 g maltodextrin three times a day), for 4 weeks |
| BG005 | Obese With NGT-Synbiotic | Obese (BMI = 30-37 kg/m2) normal glucose tolerant. Synbiotic [5 g of oligofructose + 1 g Bifidobacterium longum R0175 (4 billion colony forming unit (CFU)/g) three times a day) for 4 weeks.](streamdown:incomplete-link) |
| BG006 | Type 2 Diabetes-Placebo | Type 2 Diabetics Maltodextrin treatment as a placebo group. Maltodextrin, 6 gm three times a day for 4 weeks. |
| BG007 | Type 2 Diabetes-Sevelamer | Type 2 Diabetics Sevelamer (1.6 g sevelamer + 4.4 g maltodextrin three times a day), for 4 weeks |
| BG008 | Type 2 Diabetes-Synbiotic | Type 2 Diabetics Synbiotic [5 g of oligofructose + 1 g Bifidobacterium longum R0175 (4 billion colony forming unit (CFU)/g) three times a day) for 4 weeks.](streamdown:incomplete-link) |
| BG009 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| ID | Title | Description |
|---|---|---|
| OG000 | Lean With NGT-Placebo | Lean (BMI< 26 kg/m2) normal glucose tolerant Maltodextrin treatment as a placebo group. Maltodextrin, 6 gm three times a day for 4 weeks |
| OG001 | Lean With NGT-Sevelamer | Lean (BMI< 26 kg/m2) normal glucose tolerant Sevelamer (1.6 g sevelamer + 4.4 g maltodextrin three times a day), for 4 weeks |
| OG002 | Lean With NGT-Synbiotic | Lean (BMI< 26 kg/m2) normal glucose tolerant Synbiotic [5 g of oligofructose + 1 g Bifidobacterium longum R0175 (4 billion colony forming unit (CFU)/g) three times a day) for 4 weeks.](streamdown:incomplete-link) |
| OG003 | Obese With NGT-Placebo | Obese (BMI = 30-37 kg/m2) normal glucose tolerant. Maltodextrin treatment as a placebo group. Maltodextrin, 6 gm three times a day for 4 weeks. |
| OG004 | Obese With NGT-Sevelamer | Obese (BMI = 30-37 kg/m2) normal glucose tolerant. Sevelamer (1.6 g sevelamer + 4.4 g maltodextrin three times a day), for 4 weeks |
| OG005 | Obese With NGT-Synbiotic | Obese (BMI = 30-37 kg/m2) normal glucose tolerant. Synbiotic [5 g of oligofructose + 1 g Bifidobacterium longum R0175 (4 billion colony forming unit (CFU)/g) three times a day) for 4 weeks.](streamdown:incomplete-link) |
| OG006 | Type 2 Diabetes-Placebo | Type 2 Diabetics Maltodextrin treatment as a placebo group. Maltodextrin, 6 gm three times a day for 4 weeks. |
| OG007 | Type 2 Diabetes-Sevelamer | Type 2 Diabetics Sevelamer (1.6 g sevelamer + 4.4 g maltodextrin three times a day), for 4 weeks |
| OG008 | Type 2 Diabetes-Synbiotic | Type 2 Diabetics Synbiotic [5 g of oligofructose + 1 g Bifidobacterium longum R0175 (4 billion colony forming unit (CFU)/g) three times a day) for 4 weeks.](streamdown:incomplete-link) |
|
|
|
| Secondary | Plasma Endotoxin Level and Its Panel. | Plasma Lipopolysaccharide (LPS) after intervention period | Poor recruitment for type 2 diabetic group means few subjects analyzed. | Posted | Mean | Standard Deviation | Endotoxin units/mL | Change from baseline plasma endotoxin level and its panel during 28 days. |
|
|
|
|
| Secondary | Gut Permeability | urine lactulose: mannitol ratio. | One obese sevelamer subject was not able to complete their baseline Lactulose: Mannitol ratio assay, thus cannot evaluate pre-post effect from their study. | Posted | Mean | Standard Deviation | ratio | Change from baseline gut permeability at 24 days of the intervention. |
|
|
|
|
| 0 |
| 6 |
| 0 |
| 6 |
| 4 |
| 6 |
| EG001 | Lean With NGT-Sevelamer | Lean (BMI< 26 kg/m2) normal glucose tolerant Sevelamer (1.6 g sevelamer + 4.4 g maltodextrin three times a day), for 4 weeks | 0 | 8 | 0 | 8 | 3 | 8 |
| EG002 | Lean With NGT-Synbiotic | Lean (BMI< 26 kg/m2) normal glucose tolerant Synbiotic [5 g of oligofructose + 1 g Bifidobacterium longum R0175 (4 billion colony forming unit (CFU)/g) three times a day) for 4 weeks.](streamdown:incomplete-link) | 0 | 8 | 0 | 8 | 4 | 8 |
| EG003 | Obese With NGT-Placebo | Obese (BMI = 30-37 kg/m2) normal glucose tolerant. Maltodextrin treatment as a placebo group. Maltodextrin, 6 gm three times a day for 4 weeks. | 0 | 10 | 0 | 10 | 6 | 10 |
| EG004 | Obese With NGT-Sevelamer | Obese (BMI = 30-37 kg/m2) normal glucose tolerant. Sevelamer (1.6 g sevelamer + 4.4 g maltodextrin three times a day), for 4 weeks | 0 | 9 | 0 | 9 | 3 | 9 |
| EG005 | Obese With NGT-Synbiotic | Obese (BMI = 30-37 kg/m2) normal glucose tolerant. Synbiotic [5 g of oligofructose + 1 g Bifidobacterium longum R0175 (4 billion colony forming unit (CFU)/g) three times a day) for 4 weeks.](streamdown:incomplete-link) | 0 | 9 | 0 | 9 | 4 | 9 |
| EG006 | Type 2 Diabetes-Placebo | Type 2 Diabetics Maltodextrin treatment as a placebo group. Maltodextrin, 6 gm three times a day for 4 weeks. | 0 | 2 | 0 | 2 | 1 | 2 |
| EG007 | Type 2 Diabetes-Sevelamer | Type 2 Diabetics Sevelamer (1.6 g sevelamer + 4.4 g maltodextrin three times a day), for 4 weeks | 0 | 0 | 0 | 0 | 0 | 0 |
| EG008 | Type 2 Diabetes-Synbiotic | Type 2 Diabetics Synbiotic [5 g of oligofructose + 1 g Bifidobacterium longum R0175 (4 billion colony forming unit (CFU)/g) three times a day) for 4 weeks.](streamdown:incomplete-link) | 0 | 1 | 0 | 1 | 0 | 1 |
|
| Fibromyalgia Exacerbation | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Intermittent edema | Blood and lymphatic system disorders | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Non-systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | Non-systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Abdominal Bloating/Flatulence | Gastrointestinal disorders | Non-systematic Assessment |
|
| Headache/Lightheadedness | Nervous system disorders | Non-systematic Assessment |
|
| Yeast Infection | Renal and urinary disorders | Non-systematic Assessment |
|
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| D010829 |
| Physiological Phenomena |
| D019936 | Probiotics |
| D019602 | Food and Beverages |
| D011073 | Polyamines |
| D000588 | Amines |
| D009930 | Organic Chemicals |
Null hypothesis is that Synbiotic treated Obese subjects with normal glucose tolerance will show no post-treatment change in insulin sensitivity compared to placebo treated subjects. |
| Generalized Estimating Equation |
| >0.05 |
p-value not adjusted for multiple comparison, a priori threshold for significance set at p<0.025 for multiple comparisons. |
| Superiority |
Null hypothesis is that Synbiotic treated Obese subjects with normal glucose tolerance will show no post-treatment change in Lactulose:Mannitol ratio compared to placebo treated subjects. |
| Generalized Estimating Equation |
| >0.05 |
p-value not adjusted for multiple comparison, a priori threshold for significance set at p<0.025 for multiple comparisons. |
| Superiority |