ADI-PEG20, Obesity and Prediabetes
- Registration Number
- NCT05829239
- Lead Sponsor
- Washington University School of Medicine
- Brief Summary
Th purpose of this study is to determine whether ADI-PEG20 (PEGylated arginine deiminase), an arginine catabolizing enzyme preparation, improves insulin sensitivity, mitochondrial respiration, and energy utilization in adolescents with prediabetes.
- Detailed Description
Obesity, insulin resistance, and their complications are major causes of morbidity and mortality in children, adolescents, and adults. Although caloric restriction is an effective treatment, intensive lifestyle changes are rarely durable. The investigators and others have shown that: (i.) fasting incites arginine catabolism, and forced arginine catabolism recapitulates several therapeutic effects of fasting, (ii.) exogenous, forced arginine catabolism improves metabolic health, and (iii.) ADI-PEG20 (PEGylated arginine deiminase) is an arginine catabolizing enzyme preparation that improves insulin sensitivity, mitochondrial respiration, and energy utilization in obese mice. The study will determine whether ADI-PEG20 also exerts beneficial effects on metabolic healthy in people. The investigators will perform a 12-week, randomized, double-blind, placebo-controlled trial in boys and girls with pre-diabetes to evaluate the efficacy of ADI-PEG20 treatment on: 1) body composition; 2) resting energy expenditure; 3) multi-organ insulin sensitivity; 3) β-cell function; and 4) muscle mitochondrial function.
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- 48
- age: ≥18 and ≤22 years;
- BMI 25.0 - 44.9 kg/m2;
- Prediabetes, defined as fasting plasma glucose of ≥100 mg/dL, or HbA1C ≥5.7%, or HOMA-IR ≥2.5.
- HbA1C ≥6.5%;
- Intolerance or allergies to ingredients in ADI-PEG20 or placebo;
- Taking dietary supplements or medications known to affect our study outcomes;
- Evidence of significant organ system dysfunction or diseases,
- Metallic implants, which would preclude MRI
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Will be weekly intramuscularly for 8-week ADI-PEG20 ADI-PEG20 ADI-PEG20 (ADI-PEG20 is arginine deiminase (ADI) conjugated to polyethylene glycol (PEG) of 20,000 molecular weight) will be weekly intramuscularly at a dose of 18 mg/m2 body surface area/week for 8-week.
- Primary Outcome Measures
Name Time Method Change in insulin sensitivity Baseline and 8 weeks of ADI-PEG20 or placebo Insulin sensitivity will be assessed by using the hyperinsulinemic-euglycemic clamp procedure
- Secondary Outcome Measures
Name Time Method Change in oral glucose tolerance Baseline and 8 weeks of ADI-PEG20 or placebo Oral glucose tolerance will be assessed by measuring plasma glucose concentrations before and after ingesting 75 grams glucose
Change in β-cell function Baseline and 8 weeks of ADI-PEG20 or placebo β-cell function will be assessed from a modified oral glucose tolerance test
Change in resting energy expenditure Baseline and 8 weeks of ADI-PEG20 or placebo Resting energy expenditure (in kcal/min) will be assessed by using indirect calorimetry
Change in muscle mitochondrial respiration Baseline and 8 weeks of ADI-PEG20 or placebo Muscle mitochondrial respiration (in pmol O2/mg tissue) will be assessed by using high resolution respirometry, conducted on permeabilized muscle fibers obtained by muscle biopsy.
Change in intrahepatic triglyceride content Baseline and 8 weeks of ADI-PEG20 or placebo Intrahepatic triglyceride content will be assessed by magnetic resonance imagining (MRI)
Trial Locations
- Locations (1)
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States