Effects of Dihydroberberine (DHB) on GLP-1, Glycemic Control, Appetite, and Mood in Adults With Pre-Diabetes

Official title

A Randomized, Double-Blind, Placebo-Controlled Trial on the Effects of Dihydroberberine (DHB) on Glucagon-Like Peptide-1 (GLP-1), Glycemic Control, and Subjective Rating of Appetite and Mood/Energy in Adults With Pre-Diabetes

Overview

The goal of this clinical trial is to learn if Dihydroberberine (DHB) supplementation affects adults with pre-diabetes. The main questions it aims to answer are: Does DHB supplementation increase the concentration of GLP-1 in the blood? Does DHB supplementation affect appetite, mood, and energy levels? Does DHB supplementation affect body weight, blood sugar control and insulin? Researchers will compare DHB supplementation to a placebo (a look-alike substance that contains no drug) to see if DHB has any effect. Participants will: Take DHB or a placebo every day for 6 weeks. Participate in tests to measure GLP-1 levels, blood glucose, insulin and other markers. Have their continuous blood sugar profiles (with CGMs) monitored to see how much time their blood sugar spends in a healthy range. Rate their appetite, mood, and energy levels using a visual analog scale.

Interventions

• Dietary supplement Placebo 400 mg
  Participants will receive 4 placebo capsules daily for 6 weeks. Each capsule contains 100 mg of microcrystalline cellulose, which serves as a inactive control substance.
• Dietary supplement Dihydroberberine（DHB）400 mg
  Participants will receive 4 capsules of DHB (Dihydroberberine) 100 mg each, orally, once daily for 6 weeks. The total daily dose is 400 mg of DHB.

Primary outcome measures

• Change in Postprandial Total GLP-1 Cmax After Single Dose of DHB [Time frame: Visit 3, Day 0 (after single dose administration)]
• Change in GLP-1 Cmax From Baseline to End of Study After 6 Weeks of DHB [Time frame: Baseline to End of Study , approximately Week 6]

Secondary outcome measures (12)

• Change in Postprandial GLP-1 AUC (piAUC0-120min) After Single Dose of DHB [Time frame: 0-120 minutes post-meal at Baseline and Acute Visit 3, Day 0]
• Change in Time to Maximum Concentration (Tmax) of Postprandial GLP-1 After Single Dose of DHB [Time frame: 0-120 minutes post-meal at Baseline and Acute Visit 3, Day 0]
• Change in Fasting Total GLP-1 Levels from Baseline (day -7) to the Acute Visit 3 (day 0) [Time frame: From Baseline (Visit 2, Day -7) to Acute Visit (Visit 3, Day 0)]
• Postprandial Glucose and insulin Responses After Single Dose [Time frame: 0-120 minutes post-meal at Visit 3, Day 0]
• Change in Subjective Appetite Perceptions After Single Dose of DHB [Time frame: 0-120 minutes post-meal at Visit 3, Day 0]
• Time In/Out of Range of 24-Hour Continuous Glucose Monitoring (CGM) Glycemic Health Endpoints [Time frame: 24 hours following product intake (Visit 3, Day 0)]
• Mean Glucose and Variability of 24-Hour Continuous Glucose Monitoring (CGM) Glycemic Health Endpoints [Time frame: 24 hours following product intake (Visit 3, Day 0)]
• Change in Postprandial GLP-1 (piAUC0-120min) After 6 Weeks of Supplementation [Time frame: Baseline (Visit 2, Day -7) to End of Study (Visit 4, Day 42), approximately Week 6]
• Change in Postprandial Total GLP-1 Time to Maximum Concentration (Tmax) from Baseline to Week 6 [Time frame: Baseline (Visit 2, Day -7) to End of Study (Visit 4, Day 42), approximately Week 6]
• Change in Fasting Plasma Total GLP-1 Levels from Baseline to Week 6 [Time frame: Baseline (Visit 2, Day -7) to End of Study (Visit 4, Day 42), approximately Week 6]
• Change in Postprandial Plasma Glucose Maximum Concentration (Cmax) from Baseline After 6 Weeks of Supplementation [Time frame: Baseline (Visit 2, day 0) to End of Study (Visit 4, Day 42), approximately Week 6]
• Change in Postprandial Plasma Glucose Time to Peak Concentration (Tmax) from Baseline After 6 Weeks of Supplementation [Time frame: Baseline (Visit 2, day 0) to End of Study (Visit 4, Day 42), approximately Week 6]

Eligibility criteria

Inclusion criteria

1.35 - 65 years of age (inclusive). 2.BMI 25.0 - 35.0 kg/m2 (inclusive). 3.HbA1c 5.7% - 6.4% (39 - 47 mmol/mol, inclusive) measured at visit 1. 4.Participant has a score of 7 - 10 on the Vein Access Scale Assessment at visit 1.

5.Non-user or former user (daily use; cessation ≥12 months) of tobacco or nicotine products (e.g., cigarette smoking, vaping, chewing tobacco) within 12 months of visit 1, and has no plans to begin use during the study period.

6.Non-habitual users (i.e., daily or almost daily) of marijuana or hemp products, including CBD/THC products, and willing to abstain from use throughout the study period (topical creams/lotions are allowed).

7.Willing to wear a CGM sensor throughout study period and willing to adhere to instructions/ restrictions associated with the proper use and care of the CGM.

8.Willing to use personal smart phone with operating system capable of downloading and operating the Cronometer and Dexcom CGM apps for diet records and blood glucose, respectively.

9.Willing to adhere to all study procedures, including lifestyle considerations, and sign forms providing informed consent to participate in the study and authorization to release relevant protected health information to the Clinical Investigator.

Exclusion criteria

• Extreme Diets: Extreme dietary habits (e.g., ketogenic, vegan/vegetarian) at investigator's discretion.
• Intense Exercise: Moderate-to-intense physical training (≥5 hours/week).
• Weight Instability/Program: Recent weight changes (>4.5 kg≤90 d) or current/planned weight change program.
• Abnormal Labs: Abnormal lab test results of clinical significance at Visit 1 (one re-test allowed).
• Uncontrolled Chronic Illness: Uncontrolled or clinically important pulmonary, cardiac, hepatic, renal, endocrine (T1D/T2D excluded), hematologic, immunologic, neurologic, psychiatric, or biliary disorders.
• Clinically Important GI: Clinically important GI condition interfering with study product (e.g., IBD, celiac, weight loss surgery history).
• Uncontrolled HTN: Uncontrolled hypertension (SBP≥160 mmHg and/or DBP≥100 mmHg).
• Cancer History: History or presence of cancer in the prior 2 years (except non-melanoma skin cancer).
• Active Infection: Signs/symptoms of active infection ≤5 d of Visit 1.
• Anti-Hyperglycemics: Recent use (≤6 mo) of any prescription anti-hyperglycemic medication.
• Other Supplements: Use of dietary supplements (other than approved multivitamin) ≤14 d of Visit 1.
• Alcohol/Substance Abuse: History (≤12 months) of alcohol (>14 drinks/week) or substance abuse.
• Antibiotics: Antibiotic use ≤90 d of Visit 1.
• Regular NSAIDs: Regular use (≥3 days/week≤30 d) of anti-inflammatory medications.
• Steroid Use: Recent use (≤30 d) of oral/injectable steroids, or high-dose topical/inhaled steroids.
• Unregistered Drug: Exposure to any non-registered drug product ≤30 d prior to Visit 1
• Medication Instability: Unstable dose (≤90 d) of any other prescription medications (PRN excluded).
• Psychiatric Hospitalization: Major affective/psychiatric disorder requiring hospitalization ≤12 months prior to Visit 1.
• Recent Trauma/Surgery: Major trauma or any surgical event ≤30 d of Visit 1.
• Recent GI Prep: Endoscopy or colonoscopy preparation ≤90 d prior to Visit 1.
• Planned Surgery: Scheduled or planning elective surgical procedures during the study.
• Female Status: Pregnancy, lactation, planning pregnancy, or unwillingness to use approved contraception.
• Allergies: Known sensitivity or allergy to any study products or foods.
• Investigator Discretion: Any condition that interferes with compliance, confounds results, or presents undue risk.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Other

Study locations

United States · 1 center

• Merieux NutriSciences — Addison

Publications

• Moon JM, Ratliff KM, Hagele AM, Stecker RA, Mumford PW, Kerksick CM. Absorption Kinetics of Berberine and Dihydroberberine and Their Impact on Glycemia: A Randomized, Controlled, Crossover Pilot Trial. Nutrients. 2021 Dec 28;14(1):124. doi: 10.3390/nu14010124. PMID 35010998
• Panigrahi A, Mohanty S. Efficacy and safety of HIMABERB(R) Berberine on glycemic control in patients with prediabetes: double-blind, placebo-controlled, and randomized pilot trial. BMC Endocr Disord. 2023 Sep 7;23(1):190. doi: 10.1186/s12902-023-01442-y. PMID 37679692

Identifiers

NCT: NCT07210684 · STERLING IRB ID: 14195-EAAntoo

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗