ADI-PEG20, Obesity and Prediabetes

The Washington University

Status and phase: Withdrawn; Phase 2

Conditions: Obesity; PreDiabetes

Treatments: Biological: ADI-PEG20; Other: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT05829239

202304058

Details and patient eligibility

About

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.

Full 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.

Sex: All

Ages: 18 to 22 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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0 participants in 2 patient groups, including a placebo group

ADI-PEG20

Experimental group

Description:

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.

Treatment:

Biological: ADI-PEG20

Placebo

Placebo Comparator group

Description:

Will be weekly intramuscularly for 8-week

Treatment:

Other: Placebo