NCT07322679 - Dihydroberberine Effects on Body Composition and Metabolic Health in Healthy Adults | Crick

Eligibility

Sex: ALLMin age: 35 YearsMax age: 55 YearsHealthy volunteers:

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Inclusion Criteria: * 35 - 55 years of age (inclusive) at visit 1. * BMI ≥ 27.0 - ≤ 33.0 kg/m2. * Participant has a score of 7 - 10 on the Vein Access Scale Assessment at visit 1. * 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. * 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). * Willing to use personal smart phone with operating system capable of downloading and operating study applications (e.g., FitBit, smart scale, activity watch, etc). * Willing to adhere to all study procedures, including lifestyle considerations (see section 6.3), 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 dietary habits (e.g., ketogenic, very high protein, very high fiber, vegan/vegetarian) at the discretion of the Clinical Investigator. * Individuals undergoing moderate-to-intense activity (e.g., sports/exercise ≥ 5h/wk). * Recent weight changes (\>4.5 kg ≤ 90 d of visit 1), or current/planned engagement in a weight change program (e.g., weight loss or muscle gain) outside of the researcher-instructed, self-directed Lifestyle Intervention throughout the study period. * Abnormal laboratory test results of clinical significance at visit 1, at the discretion of the Clinical Investigator. One re-test will be allowed on a separate day prior to visit 2, for subjects with abnormal laboratory test results. * Uncontrolled and/or clinically important pulmonary (including uncontrolled asthma), cardiac (including, but not limited to, atherosclerotic disease, history of myocardial infarction, peripheral arterial disease, stroke), hepatic, renal, endocrine (including Type 1 and Type 2 diabetes mellitus), hematologic, immunologic, neurologic (such as Alzheimer's or Parkinson's disease), psychiatric (including depression and/or anxiety disorders) or biliary disorders. Conditions that are well-controlled or resolved will be assessed by the Clinical Investigator on a case-by-case basis. * Clinically important GI condition that would potentially interfere with the evaluation of the study product (e.g., inflammatory bowel disease, irritable bowel syndrome, Crohn's disease, celiac disease, history of surgery for weight loss, gastroparesis, and clinically significant lactose or gluten intolerance or other food or ingredient allergies). * Uncontrolled hypertension (systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg. Stable use (no initiation or change in dose ≤ 90 d of visit 1) of FDA-approved medications for hypertension is allowed. * History or presence of cancer in the prior 2 years, except for non-melanoma skin cancer. * Signs or symptoms of an active infection of clinical relevance ≤ 5 d of visit 1. The visit may be rescheduled once all signs and symptoms have resolved (at the discretion of the Clinical Investigator) at least 5 d prior to visit 1. * Recent use (≤ 6 mo of visit 1) of any prescription anti-hyperglycemic/weight loss medication. This includes, but is not limited to: metformin, insulin, DPP-4 inhibitors, SGLT-2 inhibitors, GLP-1 agonist, GIP agonists, Pioglitazone and Sulfonylureas. * Use of any dietary supplement, other than conventional once-daily multivitamin/mineral supplements (within limits of the DRI) ≤ 14 d of visit 1 and throughout the study. * Recent history (≤ 12 months visit 1) of alcohol or substance abuse. Alcohol abuse is defined as \>14 drinks per week (1 drink = 12 oz beer, 5 oz wine, or 1½ oz distilled spirits). * Unstable use (change in dose) of any other prescription medications ≤ 90 d of visit 1, except for medications used PRN (e.g., asthma inhalers, non-drowsy seasonal allergy medications, etc.) * Antibiotic use ≤ 90 d of visit 1 and throughout the study period. * Regular use (≥ 3 days/week ≤ 30 d of visit 1) of anti-inflammatory medications (e.g., NSAIDs) and throughout the study period. * Recent use of oral or injectable steroids, or topical or inhaled steroids (≥ 1500 µg/d) within 30 d of visit 1 and throughout the study period. * Exposure to any non-registered drug product ≤ 30 d prior to visit 1. * Diagnosed with major affective disorder, or other psychiatric disorder, that required hospitalization ≤ 12 months prior to visit 1. * Recent (≤ 90 d of visit 1) endoscopy and/or colonoscopy procedure. * Major trauma or any other surgical event ≤ 30 d of visit 1. * Currently scheduled, or planning to schedule, an elective surgical procedure during the study. * Female who is pregnant, planning to be pregnant during the study period, lactating, or is of childbearing potential and is unwilling to commit to the use of a medically approved form of contraception throughout the study period. Women who become pregnant during the study will be discontinued. General safety related criteria * Known sensitivity, intolerability, or allergy to any of the study products or study foods. * Has a condition the Clinical Investigator believes would interfere with his ability to provide informed consent, and comply with the study protocol, which might confound the interpretation of the study results, or put the participant at undue risk.

Outcomes

Primary Outcomes

Body weight

Body weight will be measured in-clinic at Baseline (Visit 2, Week 0, Day 1) and End of Study (Visit 3, Week 12, Day 84) using a calibrated digital scale under standardized conditions (fasted, light clothing, no shoes).

Time frame: Baseline (Visit 2, Week 0, Day 1) to End of the Study (Visit 3, Week 12, Day 84)

Secondary Outcomes

Plasma Glucose Positive Incremental Area Under the Curve (piAUC)

Positive incremental Area Under the Curve (piAUC0-120min) of plasma glucose following a Mixed-meal Tolerance Test (MTT) after a single dose of study product.

Time frame: Baseline (Visit 2, Day 1): t=0 to t=120 minutes

Plasma Glucose Maximum Concentration (Cmax)

Maximum concentration (Cmax) of plasma glucose following a Mixed-meal Tolerance Test (MTT) after a single dose of study product.

Time frame: Baseline (Visit 2, Day 1): t=0 to t=120 minutes

Plasma Glucose Time to Maximum Concentration (Tmax)

Time to maximum concentration (Tmax) of plasma glucose following a Mixed-meal Tolerance Test (MTT) after a single dose of study product.

Time frame: Baseline (Visit 2, Day 1): t=0 to t=120 minutes

Composite Appetite Score Net Incremental Area Under the Curve (niAUC)

Net incremental Area Under the Curve (niAUC0-120min) for the Composite Appetite Score following a Mixed-meal Tolerance Test (MTT) after a single dose of study product.

Time frame: Baseline (Visit 2, Day 1): t=0 to t=120 minutes

Net Incremental Area Under the Curve (niAUC0-120min) for Individual Appetite Visual Analog Scale (VAS) Ratings

Net incremental area under the curve (niAUC) from 0 to 120 minutes for individual appetite-related sensations measured using a 100-mm Visual Analog Scale (VAS), including Hunger, Desire to Eat, Fullness, and Prospective Food Consumption. The VAS ranges from 0 mm ("not at all") to 100 mm ("extremely"). Higher scores on Hunger, Desire to Eat, and Prospective Food Consumption indicate greater appetite drive and poorer satiety; higher scores on Fullness indicate greater satiety (better outcome).

Time frame: Baseline (Visit 2, Day 1): t=0 to t=120 minutes

Composite Appetite Score Positive Maximum Response

Maximum positive change from fasting baseline in the Composite Appetite Score, calculated as the average of standardized 100-mm Visual Analog Scale (VAS) ratings for Hunger, Desire to Eat, Fullness, and Prospective Food Consumption. The VAS ranges from 0 mm ("not at all") to 100 mm ("extremely"). Higher values for Hunger, Desire to Eat, and Prospective Food Consumption reflect increased appetite, while higher values for Fullness reflect enhanced satiety; the composite score is interpreted based on the net direction of these opposing components (better outcome).

Time frame: Baseline (Visit 2, Day 1): t=0 to t=120 minutes

Individual Appetite Visual Analog Scale (VAS) Ratings Positive Maximum Response

Maximum positive deviation from fasting baseline in individual appetite-related sensations measured using a 100-mm Visual Analog Scale (VAS) for Hunger, Desire to Eat, Fullness, and Prospective Food Consumption. The scale ranges from 0 mm ("not at all") to 100 mm ("extremely"). Higher scores on Hunger, Desire to Eat, and Prospective Food Consumption represent greater appetite and poorer satiety; higher scores on Fullness represent stronger satiety (better outcome) .

Time frame: Baseline (Visit 2, Day 1): t=0 to t=120 minutes

Energy Composite Score Net Incremental Area Under the Curve (niAUC)

Net incremental area under the curve (niAUC) from 0 to 120 minutes for the Energy Composite Score, derived as the mean of three 100-mm Visual Analog Scale (VAS) items: Energy, Vigor, and Pep. Each VAS ranges from 0 mm ("not at all") to 100 mm ("extremely"). Higher scores indicate greater perceived energy levels and are interpreted as a better outcome.

Time frame: Baseline (Visit 2, Day 1): t=0 to t=120 minutes

Energy Composite Score Positive Maximum Response

Maximum positive change from fasting baseline in the Energy Composite Score, calculated as the average of three 100-mm Visual Analog Scale (VAS) ratings: Energy, Vigor, and Pep. The VAS ranges from 0 mm ("not at all") to 100 mm ("extremely"). Higher scores reflect greater increases in subjective energy and are considered a better outcome.

Time frame: Baseline (Visit 2, Day 1): t=0 to t=120 minutes

Fatigue Composite Score Net Incremental Area Under the Curve (niAUC)

Net incremental area under the curve (niAUC) from 0 to 120 minutes for the Fatigue Composite Score, calculated as the mean of three 100-mm Visual Analog Scale (VAS) items: Fatigue, Exhaustion, and Worn-out. Each VAS ranges from 0 mm ("not at all") to 100 mm ("extremely"). Higher scores indicate greater perceived fatigue and are interpreted as a worse outcome.

Time frame: Baseline (Visit 2, Day 1): t=0 to t=120 minutes

Fatigue Composite Score Positive Maximum Response

Maximum positive change from fasting baseline in the Fatigue Composite Score, derived from the average of three 100-mm Visual Analog Scale (VAS) ratings: Fatigue, Exhaustion, and Worn-out. The VAS ranges from 0 mm ("not at all") to 100 mm ("extremely"). Higher scores reflect greater increases in perceived fatigue and are considered a worse outcome.

Time frame: Baseline (Visit 2, Day 1): t=0 to t=120 minutes

Waist Circumference (WC)

Change in in-clinic measured Waist Circumference from Baseline to the End of the Study.

Time frame: Baseline (Visit 2, Week 0, Day 1) to End of the Study (Visit 3, Week 12, Day 84)

Hip Circumference (HC)

Change in in-clinic measured Hip Circumference from Baseline to the End of the Study.

Time frame: Baseline (Visit 2, Week 0, Day 1) to End of the Study (Visit 3, Week 12, Day 84)

Waist-to-Hip Ratio (WHR)

Change in calculated Waist-to-Hip Ratio (WC/HC) from Baseline to the End of the Study.

Time frame: Baseline (Visit 2, Week 0, Day 1) to End of the Study (Visit 3, Week 12, Day 84)

Lean Mass

Change in total and regional (arms, legs, trunk) lean mass, measured via Dual-energy X-ray Absorptiometry (DXA), from Baseline to the End of the Study.

Time frame: Baseline (Visit 2, Week 0, Day 1) to End of the Study (Visit 3, Week 12, Day 84)

Fat Mass

Change in total and regional (arms, legs, trunk) fat mass, measured via DXA, from Baseline to the End of the Study.

Time frame: Baseline (Visit 2, Week 0, Day 1) to End of the Study (Visit 3, Week 12, Day 84)

Fat-Free Mass

Change in total fat-free mass, measured via DXA, from Baseline to the End of the Study.

Time frame: Baseline (Visit 2, Week 0, Day 1) to End of the Study (Visit 3, Week 12, Day 84)

Visceral Adipose Tissue (VAT)

Change in abdominal visceral fat mass and volume, measured via DXA, from Baseline to the End of the Study.

Time frame: Baseline (Visit 2, Week 0, Day 1) to End of the Study (Visit 3, Week 12, Day 84)

Fasting Plasma Glucose

Change in fasting plasma glucose levels from Baseline to the End of the Study.

Time frame: Baseline (Visit 2, Week 0, Day 1) to End of the Study (Visit 3, Week 12, Day 84)

Fasting Plasma Insulin

Change in fasting plasma insulin levels from Baseline to the End of the Study.

Time frame: Baseline (Visit 2, Week 0, Day 1) to End of the Study (Visit 3, Week 12, Day 84)

Glycated Hemoglobin (HbA1c)

Change in Glycated Hemoglobin (HbA1c) levels from Baseline to the End of the Study.

Time frame: Baseline (Visit 2, Week 0, Day 1) to End of the Study (Visit 3, Week 12, Day 84)

Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)

Change in HOMA-IR calculated from fasting glucose and insulin levels from Baseline to the End of the Study.

Time frame: Baseline (Visit 2, Week 0, Day 1) to End of the Study (Visit 3, Week 12, Day 84)

Fasting Plasma Leptin

Change in fasting plasma leptin levels from Baseline to the End of the Study.

Time frame: Baseline (Visit 2, Week 0, Day 1) to End of the Study (Visit 3, Week 12, Day 84)

Postprandial Glucose niAUC (0-120 min)

Change in postprandial glucose niAUC (0-120 min) response to an MTT from Baseline to the End of the Study.

Time frame: Baseline (Visit 2, Week 0, Day 1) to End of the Study (Visit 3, Week 12, Day 84)

Postprandial Glucose Cmax

Change in postprandial glucose Cmax response to an MTT from Baseline to the End of the Study.

Time frame: Baseline (Visit 2, Week 0, Day 1) to End of the Study (Visit 3, Week 12, Day 84)

Postprandial Glucose Tmax

Change in postprandial glucose Tmax response to an MTT from Baseline to the End of the Study.

Time frame: Baseline (Visit 2, Week 0, Day 1) to End of the Study (Visit 3, Week 12, Day 84)

Postprandial Appetite Visual Analog Scale (VAS) Net Incremental Area Under the Curve (niAUC; 0-120 minutes)

Change from baseline to end of study in the net incremental area under the curve (niAUC) over 0 to 120 minutes for postprandial appetite ratings measured using a 100-mm Visual Analog Scale (VAS), including Hunger, Desire to Eat, Fullness, and Prospective Food Consumption. The VAS ranges from 0 mm ("not at all") to 100 mm ("extremely"). Higher scores on Hunger, Desire to Eat, and Prospective Food Consumption indicate greater appetite drive and poorer satiety ; higher scores on Fullness indicate greater satiety (better outcome).

Time frame: Baseline (Visit 2, Week 0, Day 1) to End of the Study (Visit 3, Week 12, Day 84)

Postprandial Appetite Visual Analog Scale (VAS) Positive Maximum Response

Change from baseline to end of study in the positive maximum response (maximum increase from fasting value) of postprandial appetite ratings measured using a 100-mm Visual Analog Scale (VAS), including Hunger, Desire to Eat, Fullness, and Prospective Food Consumption. The VAS ranges from 0 mm ("not at all") to 100 mm ("extremely"). Higher scores on Hunger, Desire to Eat, and Prospective Food Consumption indicate greater appetite drive and poorer satiety; higher scores on Fullness indicate greater satiety (better outcome).

Time frame: Baseline (Visit 2, Week 0, Day 1) to End of the Study (Visit 3, Week 12, Day 84)

Postprandial Energy Visual Analog Scale (VAS) Net Incremental Area Under the Curve (niAUC; 0-120 min)

Change from baseline to end of study in the net incremental area under the curve (niAUC) over 0-120 minutes for postprandial energy-related ratings measured using a 100-mm Visual Analog Scale (VAS), including Energy, Vigor, and Pep. The VAS ranges from 0 mm ("not at all") to 100 mm ("extremely"). Higher niAUC values indicate greater postprandial energy enhancement and are interpreted as a better outcome.

Time frame: Baseline (Visit 2, Week 0, Day 1) to End of the Study (Visit 3, Week 12, Day 84)

Postprandial Energy Visual Analog Scale (VAS) Positive Maximum Response

Change from baseline (Week 0) to end of study (Week 12) in the incremental peak response (defined as the maximum increase from the pre-meal fasting value) for postprandial energy-related ratings. Ratings are assessed using a 100-mm Visual Analog Scale (VAS) for three items: Energy, Vigor, and Pep. The VAS ranges from 0 mm ("not at all") to 100 mm ("extremely"). Higher scores represent a greater maximal increase in perceived energy levels, indicating a better outcome.

Time frame: Baseline (Visit 2, Week 0, Day 1) to End of the Study (Visit 3, Week 12, Day 84)

Profile of Mood States -2 (POMS-2) Total and Component Scores

Change from baseline to end of study in the POMS-2 Total Mood Disturbance (TMD) score and six component subscale scores: Anger-Hostility, Confusion-Bewilderment, Depression-Dejection, Fatigue-Inertia, Tension-Anxiety, and Vigor-Activity. The POMS-2 is a validated 65-item self-report questionnaire rated on a 5-point Likert scale (0 = "Not at all" to 4 = "Extremely"). The TMD score is calculated by summing the scores of the five negative mood subscales and subtracting the Vigor-Activity score. Higher TMD and negative subscale scores reflect greater emotional distress (worse outcome), while higher Vigor-Activity scores reflect increased energy and well-being (better outcome).

Time frame: Baseline (Visit 2, Week 0, Day 1) to End of the Study (Visit 3, Week 12, Day 84)

Dihydroberberine Effects on Body Composition and Metabolic Health in Healthy Adults

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts