MOTS-c for Improving Insulin Sensitivity in Adults With Prediabetes and Overweight/Obesity
ID: NCT07505745
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This Phase 2a study evaluates whether 12 weeks of treatment with investigational MOTS-c improves insulin sensitivity compared with placebo in adults with prediabetes and overweight/obesity. Participants are randomized 1:1 to MOTS-c or placebo, receive standardized lifestyle counseling, and are followed for safety through Week 16.
Read Full Scientific Objectives & Methods
Mitochondrial-derived peptides (MDPs) are small peptides encoded by mitochondrial DNA that can act as signaling molecules. MOTS-c (mitochondrial open reading frame of the 12S rRNA type-c) has been reported to regulate insulin sensitivity and metabolic homeostasis in preclinical studies, with skeletal muscle identified as a key target tissue and AMPK activation proposed as a downstream mechanism. Based on these findings, this trial is designed to test the hypothesis that MOTS-c can improve insulin sensitivity and cardiometabolic risk markers in humans with early metabolic dysfunction. The study includes a screening period (up to 4 weeks), a 12-week double-blind treatment period, and a 4-week post-treatment safety follow-up. Efficacy is assessed using a 75 g oral glucose tolerance test (OGTT)-derived insulin sensitivity index and standard metabolic endpoints (HbA1c, fasting glucose, lipids, body weight, and waist circumference). Safety assessments include adverse events, vital signs, ECG, and laboratory testing.
Drug: MOTS-c (MDP)
Drug: Placebo
injection
Fixed dose once daily for 12 weeks
Treatment Arms Description
Participants receive investigational MOTS-c plus standardized lifestyle counseling.
Participants receive matching placebo plus standardized lifestyle counseling.
- Age 18 to 65 years at the time of consent.
- Body mass index (BMI) 27.0 to 40.0 kg/m\^2.
- Prediabetes documented at screening by any of the following: (a) HbA1c 5.7% to 6.4%; (b) fasting plasma glucose 100 to 125 mg/dL; or (c) 2-hour plasma glucose 140 to 199 mg/dL during a 75 g OGTT.
- Stable body weight (less than 5% change) for at least 3 months prior to screening.
- Willingness to maintain stable diet and physical activity patterns during the 12-week treatment period.
- For participants of childbearing potential: agreement to use highly effective contraception for the study duration and for a protocol-specified period after last dose.
- Ability to understand and sign informed consent.
- Diabetes mellitus (e.g., HbA1c 6.5% or higher, fasting plasma glucose 126 mg/dL or higher, or 2-hour glucose 200 mg/dL or higher at screening).
- Use of glucose-lowering medications (including metformin, GLP-1 receptor agonists, SGLT2 inhibitors) within 3 months prior to screening.
- History of bariatric surgery or planned weight-loss surgery during the study period.
- Clinically significant cardiovascular disease within 6 months (e.g., myocardial infarction, stroke, unstable angina) or uncontrolled hypertension.
- Estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73 m\^2, clinically significant hepatic disease, or ALT/AST \> 2.5x upper limit of normal at screening.
- Active malignancy requiring treatment (except adequately treated non-melanoma skin cancer).
- Pregnant, breastfeeding, or planning pregnancy during the study period.
- Known hypersensitivity to peptide therapeutics or any component of the investigational product formulation.
- Any condition that, in the investigator's judgment, would interfere with study participation or interpretation of results (e.g., inability to comply with study procedures).
Primary Outcome Measures
- Change from baseline in OGTT-derived insulin sensitivity (Matsuda Index) — Time Frame: 12 Weeks
- Incidence of treatment-emergent adverse events (TEAEs) — Time Frame: 16 weeks
View Secondary Outcome Measures (4)
- Change from baseline in HbA1c. — Time Frame: 12 Weeks
- Change from baseline in fasting glucose — Time Frame: 12 weeks
- Change from baseline in 2-hour plasma glucose during 75 g OGTT. — Time Frame: 12 weeks
- Immunogenicity (anti-drug antibodies, if applicable). — Time Frame: 16 weeks
This trial is recruiting at 1 study facilities worldwide. Click below to see if there is a clinic or hospital in your area:
Show All 1 Facilities & Contact Sites
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View Official Medical/Scientific Title
A Phase 2a, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety, and Pharmacodynamics of MOTS-c (a Mitochondrial-Derived Peptide) in Adults With Prediabetes and Overweight/Obesity