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

Study Overview
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Brief Summary
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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
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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.

Official Title
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An Placebo-Controlled Clinical Nutrition Study to Evaluate the Metabolic Effects of Two Medical Food Products in Subjects With Type 2 Diabetes Treated With Diet and Exercise Alone or in Combination With Metformin ± Sulfonylurea

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Other: WB-010
* Other: WB-011
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Balanced randomization across 3 arms: formulation WB-010, formulation WB-011 and placebo
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: WB-010<br>3 capsules administered twice daily with morning and evening meal for 12 weeks | Other: WB-010<br>* Medical food formulation<br>|
| Experimental: WB-011<br>3 capsules administered twice daily with morning and evening meal for 12 weeks | Other: WB-011<br>* WB-011 medical food product<br>|
| Placebo Comparator: Placebo<br>3 capsules administered twice daily with morning and evening meal for 12 weeks | Other: Placebo<br>* Placebo Capsules identical to those containing WB-010 and WB-011.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3-hour plasma glucose AUC | Change in area under plasma glucose concentration versus time curve (AUC) during standardized 3-hour Meal Tolerance Test | From Baseline to Week 12 | 
| CRP | Change in c-reactive protein concentration | From Baseline to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incremental glucose AUC | Change in area under plasma glucose concentration versus time curve (AUC) above the fasting plasma glucose level during standardized 3-hour Meal Tolerance Test | From Baseline to Week 12 | 
| Hemoglobin A1c | Change in A1c | From Baseline to Week 4 and Week 12 | 
| Fasting plasma glucose concentration | Change in fasting plasma glucose concentration | From Baseline to Weeks 4, 8 and 12 | 
| Fasting plasma insulin concentration | Change in fasting plasma insulin concentration | Baseline to Weeks 4, 8 and 12 | 
| Plasma insulin AUC | Change in area under plasma insulin concentration versus time curve (AUC) during standardized 3-hour Meal Tolerance Test | From Baseline to Week 12 | 
| Homeostatic Model Assessment (HOMA) of Insulin Resistance (IR) | Change in HOMA-IR | From Baseline to Week 12 | 
| Matsuda index | Change in Matsuda index | From Baseline to Week 12 | 
| Fasting Lipid Panel | Change in fasting serum concentrations of total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides | From Baseline to Week 12 | 
| Inflammatory markers | Change in concentrations of interleukin-6, interleukin-10, tumor growth factor-α and T-cell growth factor-beta | From Baseline to Week 12 | 
| Body weight in kilograms | Change in body weight in kilograms | From Baseline to Weeks 2, 4, 8 and 12 | 
| Body Mass Index (BMI) | BMI = weight in kg/m2 | At Baseline | 
| Waist Circumference | Change in Waist Circumference | From Baseline to Weeks 2, 4, 8 and 12 | 
| Fecal Microbiome Profile | Change in Fecal Microbiome Profile assessed by DNA sequencing | From Baseline to Week 12 | 
| Adverse Events | Number of participants with adverse events related to therapy | From Baseline to Week 12 | 
| Laboratory (Chemistry panel + CBC) Values | Number of Participants With Abnormal Laboratory Values Related to Therapy | From Baseline to Week 12 | 
| Hospital Anxiety and Depression Scale | 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. | From Baseline to Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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glucose control, inflammation, safety, microbiome