ADI-PEG20, Obesity and Prediabetes

A Randomized Trial Using ADI-PEG20 to Improve Insulin- and Energy Homeostasis in Adolescents With Obesity

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.

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.

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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