Muscle Wasting, Obesity, Obesity & Overweight
Conditions
Keywords
obesity, overweight, muscle, strength, physical performance
Brief summary
The goal of this clinical trial is to learn if BIO101 treatment can improve the muscle strength of participants males and females, aged 18 to 84 years old, suffering from obesity (BMI≥30) or overweight (BMI ≥ 27) with one or more sequelae (e.g., hypertension, dyslipidemia, obstructive sleep apnea or cardiovascular disease, but excluding diabetes), and treated with semaglutide, a GLP1 agonist for 21 weeks. The main questions it aims to answer are: * Is BIO101 administered orally improving muscle strength, as measured with knee extension strength (using isokinetic dynamometry)? * Is BIO101 administration leading to additional medical problems for patients suffering from obesity or overweight with sequelae and treated with semaglutide? After the end of the study (after last patient did the last visit at the clinic), researchers will compare the BIO101-treated arm to the placebo control arm to see if the candidate drug has an effect on muscle strength, physical function, lean body mass and health related quality of life compared to placebo. BIO101 is the candidate drug and placebo is a look-alike substance that does not contain any active drug Participants will be asked to: * Take 2 pills every morning and every evening of BIO101 or placebo orally for 21 weeks. * Simultaneously, take semaglutide for 21 weeks while being on caloric restriction, following the doctor recommendation and approved prescribing information for semaglutide, with dose increasing up to at least a dose level of 1.7 mg and a maximum dose level of 2.4 mg. * Come to investigational site at screening, baseline, week 6, 13, 21 and week 33 (12 weeks after the end of treatment) for checkups and tests. * Answer to phone calls at week 25 and 29 as well (4 and 8 weeks after the end of treatment) on global health status and quality of life.
Interventions
DRUGBIO101
Oral capsules of 175 mg BIO101 containing 20-hydroxyecdysone (20E) at 97% as the active principle
OTHERPlacebo
Oral capsules of Placebo
DRUGSemaglutide
Glucagon-like peptide-1 (GLP-1) receptor agonist
Sponsors
Biophytis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 84 Years
Healthy volunteers
No
Inclusion criteria
* Willing to participate and able to sign an ICF * BMI ≥30 or BMI ≥27 with one or more weight-associated co-morbidities (e.g. hypertension, dyslipidemia, obstructive sleep apnea or cardiovascular disease) * Start of treatment with semaglutide for weight loss at Day 3 after the start of the study treatment * Willing to maintain a diet with an average intake of at least 1 gr/kg body weight protein daily * Willing to maintain sufficient exercise, i.e. at least 150 minutes per week moderate-vigorous exercise * Body weight stable (within a 5 kg range) in the 3 months prior to enrolment * Female participants should be at least 12 months post-menopausal) or surgically sterile OR have a negative urine pregnancy test at screening and be willing to use a contraceptive method from screening to 90 days after last dose. * Based on Semaglutide long half-life, participants should consent to use a contraception method 3 months after administration of the last dose intake of semaglutide.
Exclusion criteria
* Participant not able to take medications by mouth (as capsules) * Use of disallowed concomitant medications or herbal products: Any herbal products containing 20-hydroxyecdysone and derived from Leuzea carthamoides, Cyanotis vaga, or Cyanotis arachnoidea are not allowed and any other anabolic products, GH/IGF-1 products, spironolactone, metformin, chemotherapeutic agents, antidepressants, and systemic glucocorticoids within three months prior to study enrollment or strong inhibitors of the Organic Anion Transporting Polypeptide (OATP1B3) e.g. rifampicin and cyclosporine. Use of muscle strength-supporting food supplements * Any known hypersensitivity to any of the active substances (20E), and its excipients (the study medication) and the active substance and the excipients of semaglutide. * History or present cholelithiasis or cholecystectomy from medical history or sludge or stones observed on gallbladder ultrasound or any other method. * Presence of contra-indications to semaglutide per current semaglutide Prescribing Information / Summary of Product Characteristics * Current diabetes (both insulin dependent and T2DM) * A history of chronic pancreatitis or acute pancreatitis * Previous surgical obesity treatment or planned obesity surgery during the study period * Use of anti-obesity (weight-loss) medication or use of any GLP-1 RA for diabetes within 90 days before enrollment * BMI \>40 * Uncontrolled hypertension (RR above 150/100 mmHg) * NYHA Class III or IV CHF * History of stroke, myocardial infarction, life-threatening arrhythmia, or coronary revascularization within 6 months prior to screening * Clinically significant liver disease, ALT/AST \>5x ULN, or total bilirubin \> 2x ULN, unless the patient has known Gilbert's syndrome * Neuromuscular disorder or CK \>5x ULN * Autoimmune/inflammatory disorders that may cause muscle wasting * Use of antipsychotics, amphetamines, or any other treatments that can affect weight * Clinically significant ECG abnormalities * History of major depressive disorder within the last 2 years * Any lifetime history of suicide attempt * History of any suicidal behavior in the last month * History of other severe psychiatric disorders, e.g., schizophrenia, bipolar disorder * Baseline PHQ-9 score ≥15 or any suicidal ideation of level 4 or level 5 on the Columbia-Suicide Severity Rating Scale * History or current gastroparesis (from medical history) * Patients with obesity due to other endocrinologic disorders * eGFR ≤60 mL/min/1.73 m2, based on Cockcroft \& Gault formula OR Participant requiring renal dialysis * Patients with clinically Recognized Eating Disorders * Patients with clinically significant, uncontrolled hyperthyroidism or hypothyroidism, or those with newly diagnosed thyroid disease within the past 3 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in the knee extension strength at 21 weeks | Baseline and 21 weeks | Knee extension strength will be evaluated by isokinetic dynamometry |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in the knee flexion strength at 21 weeks | Baseline and 21 weeks | Knee flexion strength will be evaluated by isokinetic dynamometry |
| Change from baseline in handgrip strength at 21 weeks | baseline and 21 weeks | Handgrip strength will be measured using a Jamar dynamometer handle. |
| Change from baseline in the 6-minute walking distance test (6MWD) at 21 weeks | Baseline and 21 weeks | The 6MWD test is measuring the distance a participant can cover within the allotted time of 6 minutes. |
| Change from baseline in Stair Climb Power Test (SCPT) at 21 weeks | Baseline and 21 weeks | The SCPT measures time (in seconds) taken to ascend and descend a flight of stairs (10 steps with a 20 cm step heigh). |
| Change from baseline of five times Sit to Stand Test (5xSST) at 21 weeks | Baseline and 21 weeks | Participants are asked to stand up and sit down 5 times, as quickly as possible. The time to complete this task is recorded. |
| Change from baseline in appendicular and total lean body mass and fat mass at 21 weeks | Baseline and 21 weeks | Body composition will be measured by Dual energy X-ray absorptiometry (DXA). |
| Change from baseline in SF-36 questionnaire at 21 weeks | Baseline and 21 weeks | The Short Form-36 (SF-36) questionnaire measures health-related quality of life. |
| Change from Baseline in WQOL-Lite-CT physical function score | Baseline and 21 weeks | The Weight-Related Quality of Life Lite Clinical Trials (WQOL-Lite-CT) instrument is a validated questionnaire designed to assess the quality of life in individuals with obesity. It contains 21 questions and cover 5 domains: physical function, self-esteem, sexual life, public distress, and work. |
| Change from baseline in body weight at 21 weeks | Baseline and 21 weeks | Body weight will be measured and reported in kg. |
| Change from baseline in BMI at 21 weeks | Baseline and 21 weeks | Height will be measured (m) and agregated to body weight (kg) to report BMI in kg/m². |
| Change from baseline in waist circumference at 21 weeks | Baseline and 21 weeks. | Waist circumference will be measured and reported in cm. |
| Change from baseline in hip circumference at 21 weeks | Baseline and 21 weeks. | Hip circumference will be measured and reported in cm. |
| Change from baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at 21 weeks | Baseline ans 21 weeks | HOMA-IR will be derived from fasting plasma glucose level (nmol/L) and fasting plasma insulin level (µU/mL). |
| Change from baseline in glycated hemoglobin (HbA1c) at 21 weeks | Baseline and 21 weeks | HbA1c will be measured from blood sample and expressed in mmol/mol. |
| Change from baseline in low-density lipoprotein (LDL) cholesterol at 21 weeks | Baseline and 21 weeks | LDL cholesterol will be measured in fasting serum and expressed in mmol/L. |
| Change from baseline in High-Dentsity Lipoprotein (HDL) cholesterol at 21 weeks | Baseline and 21 weeks. | HDL cholesterol will be measured in fasting serum and expressed in mmol/L. |
| Change from baseline in triglycerides at 21 weeks | Baseline and 21 weeks. | Triglycerides will be measured in fasting serum and expressed in mmol/l. |
| Change from baseline in systolic and diastolic pressure (SBP and DBP) at 21 weeks | Baseline and 21 weeks. | Blood pressure will be measured using a validated sphygmomanometer; SBP and DBP will be recorded in mmHg. |
Outcome results
None listed