ADI-PEG20, Obesity and Prediabetes

Washington University School of Medicine

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Conditions

Obesity PreDiabetes

Interventions

ADI-PEG20BIOLOGICAL

Intramuscular injection weekly for 8 weeks

PlaceboOTHER

Intramuscular injection weekly for 8 weeks

Eligibility

Sex: ALLMin age: 18 YearsMax age: 22 Years

Medical Language ↔ Plain English

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

Locations (1)

Washington University School of Medicine

St Louis, Missouri, United States

Outcomes

Primary Outcomes

Change in insulin sensitivity

Insulin sensitivity will be assessed by using the hyperinsulinemic-euglycemic clamp procedure

Time frame: Baseline and 8 weeks of ADI-PEG20 or placebo

Secondary Outcomes

Change in oral glucose tolerance

Oral glucose tolerance will be assessed by measuring plasma glucose concentrations before and after ingesting 75 grams glucose

Time frame: Baseline and 4 weeks of ADI-PEG20 or placebo

Change in oral glucose tolerance

Oral glucose tolerance will be assessed by measuring plasma glucose concentrations before and after ingesting 75 grams glucose

Time frame: Baseline and 8 weeks of ADI-PEG20 or placebo

Change in β-cell function

β-cell function will be assessed from a modified oral glucose tolerance test

Time frame: Baseline and 4 weeks of ADI-PEG20 or placebo

Change in β-cell function

β-cell function will be assessed from a modified oral glucose tolerance test

Time frame: Baseline and 8 weeks of ADI-PEG20 or placebo

Change in resting energy expenditure

Resting energy expenditure (in kcal/min) will be assessed by using indirect calorimetry

Time frame: Baseline and 8 weeks of ADI-PEG20 or placebo

Change in muscle mitochondrial respiration

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.

Data from ClinicalTrials.gov

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