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

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

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)..

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Other: WB-010; Other: WB-011; Other: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 76
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Torrance, California, United States, 90505
      • Science 37
    • Tustin, California, United States, 92780
      • Orange County Research Center
  • Ohio
    • Youngstown, Ohio, United States, 44505
      • Northside Medical Center
  • South Carolina
    • Mount Pleasant, South Carolina, United States, 29464
      • Coastal Carolina Research Center
  • Texas
    • Houston, Texas, United States, 77074
      • Juno Research, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pendulum Therapeutics
• Investigators: Principal Investigator: Orville G Kolterman, MD, Pendulum Therapeutics

Publications and helpful links

General Publications

• Perraudeau F, McMurdie P, Bullard J, Cheng A, Cutcliffe C, Deo A, Eid J, Gines J, Iyer M, Justice N, Loo WT, Nemchek M, Schicklberger M, Souza M, Stoneburner B, Tyagi S, Kolterman O. Improvements to postprandial glucose control in subjects with type 2 diabetes: a multicenter, double blind, randomized placebo-controlled trial of a novel probiotic formulation. BMJ Open Diabetes Res Care. 2020 Jul;8(1):e001319. doi: 10.1136/bmjdrc-2020-001319.

Study record dates

Study Major Dates

• Study Start (Actual): October 22, 2017
• Primary Completion (Actual): August 16, 2018
• Study Completion (Actual): September 14, 2018

Study Registration Dates

• First Submitted: March 13, 2019
• First Submitted That Met QC Criteria: March 25, 2019
• First Posted (Actual): March 28, 2019

Study Record Updates

• Last Update Posted (Actual): February 27, 2020
• Last Update Submitted That Met QC Criteria: February 25, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: safety; inflammation; glucose control; microbiome
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: WB201-202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No