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Placebo-Controlled Clinical Nutrition Study of the Safety and Metabolic Effects of Two Medical Foods in Type 2 Diabetes

Not Applicable
Completed
Conditions
Type 2 Diabetes Mellitus
Interventions
Other: Placebo
Other: WB-011
Other: WB-010
Registration Number
NCT03893422
Lead Sponsor
Pendulum Therapeutics
Brief Summary

This 16 week placebo-controlled study evaluates the safety and impact of two medical food study products, WBF10 and WBF11, consisting of commensal microbes. The primary endpoints were safety, glucose AUC during meal tolerance test and C reactive protein (CRP)..

Detailed Description

Targeting the microbiome for treating metabolic syndrome has been gaining traction with multiple population studies demonstrating a difference between healthy individuals and patients with metabolic syndrome. Whole Biome has identified and created two medical food formulations (MFFs) aimed at improving metabolic syndrome via two mechanisms of action targeting the microbiome: (1) increasing butyrate production and (2) increasing mucin regulation.

This randomized, parallel-group, placebo-controlled, double-blinded study assesses the safety and metabolic effects of 2 MFFs on glucose control and the generalized inflammatory state associated with Type 2 Diabetes. The microbes have been fully characterized, certified as Generally Recognized As Safe (GRAS) and manufactured to Good Manufacturing Practice (GMP) standards. The target population was patients with Type 2 Diabetes who either had not been treated with antidiabetic agents or treated with metformin +/- a sulfonylurea. Subjects were randomized in a balanced manner to receive capsules containing placebo, WBF10 or WBF11.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
76
Inclusion Criteria
  • Type 2 diabetes treated with diet and exercise alone or in combination with metformin and/or sulfonylurea

  • If treated with metformin and/or sulfonylurea, must have been on a stable dose of the drug(s) for a minimum of 3 months with a stable A1c value

  • If treated with diet and exercise alone, must have one of the following:

    • Documented fasting plasma glucose >126 mg/dL
    • A1c value ≥6.8%
  • If treated with diet and exercise + metformin and/or sulfonylurea, must have a stable A1c between 6.8% and 11.0% for 3 months prior study entry

  • BMI >25 but <45 and weight stable within +/- 5% over past 3 months

  • If female, must meet all the following criteria:

    • Not pregnant or breastfeeding
    • If of childbearing potential (including peri-menopausal women with menstruation during past year) must practice and be willing to continue appropriate birth control during the entire duration of the study
  • Have a home freezer available for immediate freezing of stool samples

  • Able to read, understand, and sign the informed consent form (ICF) and HIPAA authorization when applicable,

  • Able to communicate with the investigator, and understand and comply with protocol requirements

Exclusion Criteria
  • Use of antibiotic, antifungal, antiparasitic, or antiviral therapy within 30 days prior to study entry

  • Planned use or antibiotic, antifungal, antiparasitic, or antiviral treatment during the study period

  • Subjects using a proton pump inhibitor must be on a stable dose that will be maintained throughout the study period

  • Present use of probiotics/nutritional supplements. (Note: Use of replacement doses of Vitamin D, calcium supplements, and a single daily multi-vitamin tablet allowed)

  • Participation in a structured weight-loss program within the past 2 months

  • Change in body weight ≥5% within the past month

  • Excess alcohol consumption; with an alcoholic drink defined as 12 fluid ounces of beer (5% alcohol), 5 fluid ounces of wine (12% alcohol) or 1.5 fluid ounces of 80 proof distilled spirits

    • Women: More than 2 alcoholic drinks/day or more than 7 drinks/week
    • Men: More than 3 alcoholic drinks/day or more than 10 drinks/week
  • Travel outside United States within 30 days of study entry

  • Planned travel outside United States during study period

  • Use of an experimental drug within 30 days prior to study entry

  • Known milk, peanut, tree nut, wheat, soy or shellfish allergy

  • Diagnosis of a sexually transmitted disease including, but not limited to, HIV, syphilis, herpes, gonorrhea, hepatitis A, hepatitis B, and hepatitis C

  • Hospitalization during last 3 months (Same day surgery center procedures allowed)

  • Active GI disease

  • Gastrointestinal tract surgery (appendectomy and cholecystectomy allowed)

  • Cystic fibrosis

  • Any condition deemed by the investigator to disqualify subject

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlacebo3 capsules administered twice daily with morning and evening meal for 12 weeks
WB-011WB-0113 capsules administered twice daily with morning and evening meal for 12 weeks
WB-010WB-0103 capsules administered twice daily with morning and evening meal for 12 weeks
Primary Outcome Measures
NameTimeMethod
CRPFrom Baseline to Week 12

Change in c-reactive protein concentration

3-hour plasma glucose AUCFrom Baseline to Week 12

Change in area under plasma glucose concentration versus time curve (AUC) during standardized 3-hour Meal Tolerance Test

Secondary Outcome Measures
NameTimeMethod
Body Mass Index (BMI)At Baseline

BMI = weight in kg/m2

Waist CircumferenceFrom Baseline to Weeks 2, 4, 8 and 12

Change in Waist Circumference

Fecal Microbiome ProfileFrom Baseline to Week 12

Change in Fecal Microbiome Profile assessed by DNA sequencing

Fasting plasma glucose concentrationFrom Baseline to Weeks 4, 8 and 12

Change in fasting plasma glucose concentration

Incremental glucose AUCFrom Baseline to Week 12

Change in area under plasma glucose concentration versus time curve (AUC) above the fasting plasma glucose level during standardized 3-hour Meal Tolerance Test

Fasting plasma insulin concentrationBaseline to Weeks 4, 8 and 12

Change in fasting plasma insulin concentration

Matsuda indexFrom Baseline to Week 12

Change in Matsuda index

Fasting Lipid PanelFrom Baseline to Week 12

Change in fasting serum concentrations of total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides

Inflammatory markersFrom Baseline to Week 12

Change in concentrations of interleukin-6, interleukin-10, tumor growth factor-α and T-cell growth factor-beta

Adverse EventsFrom Baseline to Week 12

Number of participants with adverse events related to therapy

Laboratory (Chemistry panel + CBC) ValuesFrom Baseline to Week 12

Number of Participants With Abnormal Laboratory Values Related to Therapy

Hospital Anxiety and Depression ScaleFrom Baseline to Week 12

Subjects respond to 14 questions; 7 anxiety focused and 7 depression focused. Responses of "not at all", "not much", "sometimes" and "definitely" are translated to a numerical score of 0 to 4 respectively. For 2 of the depression related questions, the scoring scale is reversed. The individual numerical scores are added to provide an overall score which is interpreted as follows: 0 to 7 graded a non-case, 8 to 10 graded a borderline case and 11+ graded a case. An increase in the overall numerical score from baseline to Week 12 represents worsening and a decrease in the numerical score from baseline to Week 12 represents improvement.

Hemoglobin A1cFrom Baseline to Week 4 and Week 12

Change in A1c

Plasma insulin AUCFrom Baseline to Week 12

Change in area under plasma insulin concentration versus time curve (AUC) during standardized 3-hour Meal Tolerance Test

Homeostatic Model Assessment (HOMA) of Insulin Resistance (IR)From Baseline to Week 12

Change in HOMA-IR

Body weight in kilogramsFrom Baseline to Weeks 2, 4, 8 and 12

Change in body weight in kilograms

Trial Locations

Locations (5)

Coastal Carolina Research Center

🇺🇸

Mount Pleasant, South Carolina, United States

Science 37

🇺🇸

Torrance, California, United States

Orange County Research Center

🇺🇸

Tustin, California, United States

Northside Medical Center

🇺🇸

Youngstown, Ohio, United States

Juno Research, LLC

🇺🇸

Houston, Texas, United States

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