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MicroB2: Mechanism of Microbiome-induced Insulin Resistance in Humans (Aim2)

Sponsor
The University of Texas Health Science Center at San Antonio (Other)
Overall Status
Completed
CT.gov ID
NCT02127125
Collaborator
American Diabetes Association (Other)
69
Enrollment
1
Location
9
Arms
53
Actual Duration (Months)
1.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
69 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
Mechanism of Microbiome-induced Insulin Resistance in Humans (Aim2)
Actual Study Start Date :
Apr 10, 2014
Actual Primary Completion Date :
Sep 1, 2018
Actual Study Completion Date :
Sep 10, 2018

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: Type2 Diabetes Mellitus - Placebo

Type 2 Diabetes Mellitus subjects will receive maltodextrin (placebo)

Drug: Maltodextrin
Maltodextrin treatment as a placebo group. Maltodextrin, 6 gm three times a day for 4 weeks.
Placebo Comparator: Obese with NGT - Placebo

Obese (BMI = 30-37 kg/m2) normal glucose tolerant (NGT) subjects will receive maltodextrin (placebo)

Drug: Maltodextrin
Maltodextrin treatment as a placebo group. Maltodextrin, 6 gm three times a day for 4 weeks.
Placebo Comparator: Lean with NGT -Placebo

Lean (BMI< 26 kg/m2) normal glucose tolerant (NGT) will receive maltodextrin (placebo)

Drug: Maltodextrin
Maltodextrin treatment as a placebo group. Maltodextrin, 6 gm three times a day for 4 weeks.
Active Comparator: Type2 Diabetes Mellitus - Synbiotic

Type 2 Diabetic subjects will receive synbiotic

Drug: Synbiotic
Synbiotic [5 g of oligofructose + 1 g Bifidobacterium longum R0175 (4 billion colony forming unit (CFU)/g) three times a day) for 4 weeks.
Active Comparator: Type2 Diabetes Mellitus - Sevelamer

Type 2 Diabetic subjects will receive sevelamer

Drug: Sevelamer
Sevelamer (1.6 g sevelamer + 4.4 g maltodextrin three times a day), for 4 weeks
Other Names:
  • Renvela

    		•
    Active Comparator: Obese with NGT - Synbiotic

    Obese (BMI = 30-37 kg/m2) normal glucose tolerant subjects (NGT) will receive Synbiotic

    Drug: Synbiotic
    Synbiotic [5 g of oligofructose + 1 g Bifidobacterium longum R0175 (4 billion colony forming unit (CFU)/g) three times a day) for 4 weeks.
    Active Comparator: Obese with NGT - Sevelamer

    Obese subjects (BMI = 30-37 kg/m2) normal glucose tolerant (NGT) will receive Sevelamer

    Drug: Sevelamer
    Sevelamer (1.6 g sevelamer + 4.4 g maltodextrin three times a day), for 4 weeks
    Other Names:
  • Renvela

    		•
    Active Comparator: Lean with NGT - Synbiotic

    Lean (BMI< 26 kg/m2) normal glucose tolerant (NGT) will receive Synbiotic

    Drug: Synbiotic
    Synbiotic [5 g of oligofructose + 1 g Bifidobacterium longum R0175 (4 billion colony forming unit (CFU)/g) three times a day) for 4 weeks.
    Active Comparator: Lean with NGT - Sevelamer

    Lean (BMI< 26 kg/m2) normal glucose tolerant (NGT) will receive Sevelamer

    Drug: Sevelamer
    Sevelamer (1.6 g sevelamer + 4.4 g maltodextrin three times a day), for 4 weeks
    Other Names:
  • Renvela

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Insulin Sensitivity [Change from baseline insulin sensitivity at 28 days of the intervention.]

      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.

    Secondary Outcome Measures

    1. Plasma Endotoxin Level and Its Panel. [Change from baseline plasma endotoxin level and its panel during 28 days.]

      Plasma Lipopolysaccharide (LPS) after intervention period

    2. Gut Permeability [Change from baseline gut permeability at 24 days of the intervention.]

      urine lactulose: mannitol ratio.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:

    • Both genders (50%, male). 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 results of 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.

    Exclusion 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.

    • 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.

    • 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Audie L. Murphy VA Hospital, STVHCS San Antonio Texas United States 78229

    Sponsors and Collaborators

    • The University of Texas Health Science Center at San Antonio
    • American Diabetes Association

    Investigators

    • Principal Investigator: Nicolas Musi, MD., The University of Texas Health Science Center at San Antonio

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    The University of Texas Health Science Center at San Antonio
    ClinicalTrials.gov Identifier:
    NCT02127125
    Other Study ID Numbers:
    • HSC20130458H
    First Posted:
    Apr 30, 2014
    Last Update Posted:
    Sep 11, 2020
    Last Verified:
    Aug 1, 2020
    Additional relevant MeSH terms:
    Insulin Resistance
    Sevelamer

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail 69 participants were screened, 8 were screen failures, so not randomized.
    Arm/Group Title Lean With NGT-Placebo Lean With NGT-Sevelamer Lean With NGT-Synbiotic Obese With NGT-Placebo Obese With NGT-Sevelamer Obese With NGT-Synbiotic Type 2 Diabetes -Placebo Type 2 Diabetes-Sevelamer Type 2 Diabetes-Synbiotic
    Arm/Group Description Lean (BMI< 26 kg/m2) normal glucose tolerant Maltodextrin treatment as a placebo group. Maltodextrin, 6 gm three times a day for 4 weeks. Lean (BMI< 26 kg/m2) normal glucose tolerant Sevelamer (1.6 g sevelamer + 4.4 g maltodextrin three times a day), for 4 weeks 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. 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 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 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. Type 2 Diabetics Maltodextrin treatment as a placebo group. Maltodextrin, 6 gm three times a day for 4 weeks. Type 2 Diabetics Sevelamer (1.6 g sevelamer + 4.4 g maltodextrin three times a day), for 4 weeks 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.
    Period Title: Overall Study
    STARTED 6 8 9 11 12 12 2 0 1
    COMPLETED 6 8 8 10 9 9 2 0 1
    NOT COMPLETED 0 0 1 1 3 3 0 0 0

    Baseline Characteristics

    Arm/Group Title Lean With NGT-Placebo Lean With NGT-Sevelamer Lean With NGT-Synbiotic Obese With NGT-Placebo Obese With NGT-Sevelamer Obese With NGT-Synbiotic Type 2 Diabetes-Placebo Type 2 Diabetes-Sevelamer Type 2 Diabetes-Synbiotic Total
    Arm/Group Description Lean (BMI< 26 kg/m2) normal glucose tolerant Maltodextrin treatment as a placebo group. Maltodextrin, 6 gm three times a day for 4 weeks. Lean (BMI< 26 kg/m2) normal glucose tolerant Sevelamer (1.6 g sevelamer + 4.4 g maltodextrin three times a day), for 4 weeks 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. 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. 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 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. Type 2 Diabetics Maltodextrin treatment as a placebo group. Maltodextrin, 6 gm three times a day for 4 weeks. Type 2 Diabetics Sevelamer (1.6 g sevelamer + 4.4 g maltodextrin three times a day), for 4 weeks 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. Total of all reporting groups
    Overall Participants 6 8 8 10 9 9 2 0 1 53
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    NaN
    0
    0%
    0
    0%
    Between 18 and 65 years
    6
    100%
    7
    87.5%
    8
    100%
    10
    100%
    8
    88.9%
    9
    100%
    2
    100%
    0
    NaN
    1
    100%
    51
    96.2%
    >=65 years
    0
    0%
    1
    12.5%
    0
    0%
    0
    0%
    1
    11.1%
    0
    0%
    0
    0%
    0
    NaN
    0
    0%
    2
    3.8%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    38.8
    (14.3)
    46.9
    (15.7)
    48.8
    (12.7)
    51.6
    (9.5)
    51.7
    (12.4)
    50.3
    (8.4)
    61.0
    (1.4)
    52.0
    (0.0)
    49.2
    (12.1)
    Sex: Female, Male (Count of Participants)
    Female
    4
    66.7%
    5
    62.5%
    6
    75%
    8
    80%
    6
    66.7%
    6
    66.7%
    1
    50%
    0
    NaN
    1
    100%
    37
    69.8%
    Male
    2
    33.3%
    3
    37.5%
    2
    25%
    2
    20%
    3
    33.3%
    3
    33.3%
    1
    50%
    0
    NaN
    0
    0%
    16
    30.2%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    2
    33.3%
    4
    50%
    4
    50%
    6
    60%
    6
    66.7%
    6
    66.7%
    0
    0%
    0
    NaN
    1
    100%
    29
    54.7%
    Not Hispanic or Latino
    4
    66.7%
    4
    50%
    4
    50%
    4
    40%
    3
    33.3%
    3
    33.3%
    2
    100%
    0
    NaN
    0
    0%
    24
    45.3%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    NaN
    0
    0%
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    6
    100%
    8
    100%
    8
    100%
    10
    100%
    9
    100%
    9
    100%
    2
    100%
    1
    Infinity
    53
    5300%

    Outcome Measures

    1. Primary Outcome
    Title Insulin Sensitivity
    Description 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.
    Time Frame Change from baseline insulin sensitivity at 28 days of the intervention.

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Lean With NGT-Placebo Lean With NGT-Sevelamer Lean With NGT-Synbiotic Obese With NGT-Placebo Obese With NGT-Sevelamer Obese With NGT-Synbiotic Type 2 Diabetes-Placebo Type 2 Diabetes-Sevelamer Type 2 Diabetes-Synbiotic
    Arm/Group Description Lean (BMI< 26 kg/m2) normal glucose tolerant Maltodextrin treatment as a placebo group. Maltodextrin, 6 gm three times a day for 4 weeks Lean (BMI< 26 kg/m2) normal glucose tolerant Sevelamer (1.6 g sevelamer + 4.4 g maltodextrin three times a day), for 4 weeks 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. 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. 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 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. Type 2 Diabetics Maltodextrin treatment as a placebo group. Maltodextrin, 6 gm three times a day for 4 weeks. Type 2 Diabetics Sevelamer (1.6 g sevelamer + 4.4 g maltodextrin three times a day), for 4 weeks 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.
    Measure Participants 6 8 8 10 9 9 2 0 1
    Mean (Standard Deviation) [M Value (mg/kg/min)]
    10.16
    (3.78)
    8.45
    (2.25)
    9.47
    (2.59)
    5.96
    (2.24)
    8.14
    (2.138)
    5.45
    (1.88)
    3.81
    (.386)
    1.42
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Obese With NGT-Placebo, Obese With NGT-Sevelamer
    Comments Null hypothesis is that Sevelamer treated Obese subjects with normal glucose tolerance will show no post-treatment change in insulin sensitivity compared to placebo treated subjects.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.025
    Comments p-value not adjusted for multiple comparison, a priori threshold for significance set at p<0.025 for multiple comparisons.
    Method Generalized Estimating Equation
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Obese With NGT-Placebo, Obese With NGT-Synbiotic
    Comments 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.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value >0.05
    Comments p-value not adjusted for multiple comparison, a priori threshold for significance set at p<0.025 for multiple comparisons.
    Method Generalized Estimating Equation
    Comments
    2. Secondary Outcome
    Title Plasma Endotoxin Level and Its Panel.
    Description Plasma Lipopolysaccharide (LPS) after intervention period
    Time Frame Change from baseline plasma endotoxin level and its panel during 28 days.

    Outcome Measure Data

    Analysis Population Description
    Poor recruitment for type 2 diabetic group means few subjects analyzed.
    Arm/Group Title Lean With NGT-Placebo Lean With NGT-Sevelamer Lean With NGT-Synbiotic Obese With NGT-Placebo Obese With NGT-Sevelamer Obese With NGT-Synbiotic Type 2 Diabetes-Placebo Type 2 Diabetes-Sevelamer Type 2 Diabetes-Synbiotic
    Arm/Group Description Lean (BMI< 26 kg/m2) normal glucose tolerant Maltodextrin treatment as a placebo group. Maltodextrin, 6 gm three times a day for 4 weeks Lean (BMI< 26 kg/m2) normal glucose tolerant Sevelamer (1.6 g sevelamer + 4.4 g maltodextrin three times a day), for 4 weeks 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. 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. 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 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. Type 2 Diabetics Maltodextrin treatment as a placebo group. Maltodextrin, 6 gm three times a day for 4 weeks. Type 2 Diabetics Sevelamer (1.6 g sevelamer + 4.4 g maltodextrin three times a day), for 4 weeks 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.
    Measure Participants 6 8 8 10 8 9 1 0 1
    Mean (Standard Deviation) [Endotoxin units/mL]
    0.4452
    (0.1987)
    0.5634
    (0.1713)
    0.6925
    (0.5907)
    0.6230
    (0.1976)
    0.8012
    (0.4187)
    0.7195
    (0.2905)
    0.2961
    0.4062
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Obese With NGT-Placebo, Obese With NGT-Sevelamer
    Comments Null hypothesis is that Sevelamer treated Obese subjects with normal glucose tolerance will show no post-treatment change in insulin sensitivity compared to placebo treated subjects.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value >0.05
    Comments p-value not adjusted for multiple comparison, a priori threshold for significance set at p<0.025 for multiple comparisons.
    Method Generalized Estimating Equation
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Obese With NGT-Placebo, Obese With NGT-Synbiotic
    Comments 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.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value >0.05
    Comments p-value not adjusted for multiple comparison, a priori threshold for significance set at p<0.025 for multiple comparisons.
    Method Generalized Estimating Equation
    Comments
    3. Secondary Outcome
    Title Gut Permeability
    Description urine lactulose: mannitol ratio.
    Time Frame Change from baseline gut permeability at 24 days of the intervention.

    Outcome Measure Data

    Analysis Population Description
    One obese sevelamer subject was not able to complete their baseline Lactulose: Mannitol ratio assay, thus cannot evaluate pre-post effect from their study.
    Arm/Group Title Lean With NGT-Placebo Lean With NGT-Sevelamer Lean With NGT-Synbiotic Obese With NGT-Placebo Obese With NGT-Sevelamer Obese With NGT-Synbiotic Type 2 Diabetes-Placebo Type 2 Diabetes-Sevelamer Type 2 Diabetes-Synbiotic
    Arm/Group Description Lean (BMI< 26 kg/m2) normal glucose tolerant Maltodextrin treatment as a placebo group. Maltodextrin, 6 gm three times a day for 4 weeks Lean (BMI< 26 kg/m2) normal glucose tolerant Sevelamer (1.6 g sevelamer + 4.4 g maltodextrin three times a day), for 4 weeks 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. 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. 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 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. Type 2 Diabetics Maltodextrin treatment as a placebo group. Maltodextrin, 6 gm three times a day for 4 weeks. Type 2 Diabetics Sevelamer (1.6 g sevelamer + 4.4 g maltodextrin three times a day), for 4 weeks 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.
    Measure Participants 6 8 8 10 8 9 2 0 1
    Mean (Standard Deviation) [ratio]
    0.02262
    (0.006856)
    0.02164
    (0.008943)
    0.02349
    (0.008680)
    0.02055
    (0.01018)
    0.01635
    (0.006882)
    0.01952
    (0.004869)
    0.02662
    (0.004186)
    0.01979
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Obese With NGT-Placebo, Obese With NGT-Sevelamer
    Comments Null hypothesis is that Sevelamer treated Obese subjects with normal glucose tolerance will show no post-treatment change in Lactulose:Mannitol ratio compared to placebo treated subjects.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value >0.05
    Comments p-value not adjusted for multiple comparison, a priori threshold for significance set at p<0.025 for multiple comparisons.
    Method Generalized Estimating Equation
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Obese With NGT-Placebo, Obese With NGT-Synbiotic
    Comments 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.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value >0.05
    Comments p-value not adjusted for multiple comparison, a priori threshold for significance set at p<0.025 for multiple comparisons.
    Method Generalized Estimating Equation
    Comments

    Adverse Events

    Time Frame Study participants were enrolled in the study for approximately 2-3 months.
    Adverse Event Reporting Description 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.
    Arm/Group Title Lean With NGT-Placebo Lean With NGT-Sevelamer Lean With NGT-Synbiotic Obese With NGT-Placebo Obese With NGT-Sevelamer Obese With NGT-Synbiotic Type 2 Diabetes-Placebo Type 2 Diabetes-Sevelamer Type 2 Diabetes-Synbiotic
    Arm/Group Description Lean (BMI< 26 kg/m2) normal glucose tolerant Maltodextrin treatment as a placebo group. Maltodextrin, 6 gm three times a day for 4 weeks Lean (BMI< 26 kg/m2) normal glucose tolerant Sevelamer (1.6 g sevelamer + 4.4 g maltodextrin three times a day), for 4 weeks 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. 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. 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 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. Type 2 Diabetics Maltodextrin treatment as a placebo group. Maltodextrin, 6 gm three times a day for 4 weeks. Type 2 Diabetics Sevelamer (1.6 g sevelamer + 4.4 g maltodextrin three times a day), for 4 weeks 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.
    All Cause Mortality
    Lean With NGT-Placebo Lean With NGT-Sevelamer Lean With NGT-Synbiotic Obese With NGT-Placebo Obese With NGT-Sevelamer Obese With NGT-Synbiotic Type 2 Diabetes-Placebo Type 2 Diabetes-Sevelamer Type 2 Diabetes-Synbiotic
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/6 (0%) 0/8 (0%) 0/8 (0%) 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/2 (0%) 0/0 (NaN) 0/1 (0%)
    Serious Adverse Events
    Lean With NGT-Placebo Lean With NGT-Sevelamer Lean With NGT-Synbiotic Obese With NGT-Placebo Obese With NGT-Sevelamer Obese With NGT-Synbiotic Type 2 Diabetes-Placebo Type 2 Diabetes-Sevelamer Type 2 Diabetes-Synbiotic
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/6 (0%) 0/8 (0%) 0/8 (0%) 0/10 (0%) 0/9 (0%) 0/9 (0%) 0/2 (0%) 0/0 (NaN) 0/1 (0%)
    Other (Not Including Serious) Adverse Events
    Lean With NGT-Placebo Lean With NGT-Sevelamer Lean With NGT-Synbiotic Obese With NGT-Placebo Obese With NGT-Sevelamer Obese With NGT-Synbiotic Type 2 Diabetes-Placebo Type 2 Diabetes-Sevelamer Type 2 Diabetes-Synbiotic
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 4/6 (66.7%) 3/8 (37.5%) 4/8 (50%) 6/10 (60%) 3/9 (33.3%) 4/9 (44.4%) 1/2 (50%) 0/0 (NaN) 0/1 (0%)
    Blood and lymphatic system disorders
    Intermittent edema 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/10 (0%) 0 1/9 (11.1%) 1 0/9 (0%) 0 0/2 (0%) 0 0/0 (NaN) 0 0/1 (0%) 0
    Gastrointestinal disorders
    Nausea 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 2/10 (20%) 2 0/9 (0%) 0 0/9 (0%) 0 0/2 (0%) 0 0/0 (NaN) 0 0/1 (0%) 0
    Diarrhea 1/6 (16.7%) 1 1/8 (12.5%) 1 1/8 (12.5%) 1 0/10 (0%) 0 1/9 (11.1%) 1 0/9 (0%) 0 0/2 (0%) 0 0/0 (NaN) 0 0/1 (0%) 0
    Abdominal Bloating/Flatulence 0/6 (0%) 0 0/8 (0%) 0 1/8 (12.5%) 1 2/10 (20%) 2 1/9 (11.1%) 1 1/9 (11.1%) 1 0/2 (0%) 0 0/0 (NaN) 0 0/1 (0%) 0
    Musculoskeletal and connective tissue disorders
    Fibromyalgia Exacerbation 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/10 (0%) 0 1/9 (11.1%) 1 0/9 (0%) 0 0/2 (0%) 0 0/0 (NaN) 0 0/1 (0%) 0
    Nervous system disorders
    Headache/Lightheadedness 2/6 (33.3%) 2 0/8 (0%) 0 0/8 (0%) 0 1/10 (10%) 1 0/9 (0%) 0 1/9 (11.1%) 1 0/2 (0%) 0 0/0 (NaN) 0 0/1 (0%) 0
    Renal and urinary disorders
    Yeast Infection 1/6 (16.7%) 1 0/8 (0%) 0 0/8 (0%) 0 0/10 (0%) 0 0/9 (0%) 0 0/9 (0%) 0 0/2 (0%) 0 0/0 (NaN) 0 0/1 (0%) 0
    Skin and subcutaneous tissue disorders
    Pruritus 0/6 (0%) 0 1/8 (12.5%) 1 0/8 (0%) 0 1/10 (10%) 1 0/9 (0%) 0 0/9 (0%) 0 0/2 (0%) 0 0/0 (NaN) 0 0/1 (0%) 0
    Surgical and medical procedures
    Biopsy Site Pain/soreness 1/6 (16.7%) 1 1/8 (12.5%) 2 3/8 (37.5%) 3 3/10 (30%) 4 1/9 (11.1%) 1 2/9 (22.2%) 2 1/2 (50%) 1 0/0 (NaN) 0 0/1 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr. Nicolas Musi
    Organization San Antonio Geriatric Research, Education, and Clinical Center
    Phone (210) 562-6140
    Email musi@uthscsa.edu
    Responsible Party:
    The University of Texas Health Science Center at San Antonio
    ClinicalTrials.gov Identifier:
    NCT02127125
    Other Study ID Numbers:
    • HSC20130458H
    First Posted:
    Apr 30, 2014
    Last Update Posted:
    Sep 11, 2020
    Last Verified:
    Aug 1, 2020