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

• ClinicalTrials.gov Identifier: NCT03893422
• Recruitment Status: Completed
• First Posted: March 28, 2019
• Last Update Posted: February 27, 2020
• Sponsor: Pendulum Therapeutics
• Information provided by (Responsible Party): Pendulum Therapeutics

Study Description

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)..

Condition or disease	Intervention/treatment	Phase
Type 2 Diabetes Mellitus	Other: WB-010; Other: WB-011; Other: Placebo	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 76 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Balanced randomization across 3 arms: formulation WB-010, formulation WB-011 and placebo
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Study product was provided for each arm in identical capsules
• Primary Purpose: Other
• Official Title: 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
• Actual Study Start Date: October 22, 2017
• Actual Primary Completion Date: August 16, 2018
• Actual Study Completion Date: September 14, 2018

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. 3-hour plasma glucose AUC [ Time Frame: From Baseline to Week 12 ]
   Change in area under plasma glucose concentration versus time curve (AUC) during standardized 3-hour Meal Tolerance Test
2. CRP [ Time Frame: From Baseline to Week 12 ]
   Change in c-reactive protein concentration

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, California

Science 37

Torrance, California, United States, 90505

Orange County Research Center

Tustin, California, United States, 92780

United States, Ohio

Northside Medical Center

Youngstown, Ohio, United States, 44505

United States, South Carolina

Coastal Carolina Research Center

Mount Pleasant, South Carolina, United States, 29464

United States, Texas

Juno Research, LLC

Houston, Texas, United States, 77074

Sponsors and Collaborators

Pendulum Therapeutics

Investigators

• Principal Investigator: Orville G Kolterman, MD; Pendulum Therapeutics

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Pendulum Therapeutics
• ClinicalTrials.gov Identifier: NCT03893422
• Other Study ID Numbers: WB201-202
• First Posted: March 28, 2019
• Last Update Posted: February 27, 2020
• Last Verified: February 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Pendulum Therapeutics:

glucose control; inflammation; safety; microbiome

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases