Clinical trial NCT05829239: ADI-PEG20, Obesity and Prediabetes
Official title: A Randomized Trial Using ADI-PEG20 to Improve Insulin- and Energy Homeostasis in Adolescents With Obesity
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Obesity
PreDiabetes
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: Children's Discovery Institute
name: Polaris Pharmaceuticals, Inc.
First posted: 2023-04-25
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 22
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Single-center, randomized, double-blind, placebo-controlled study
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in insulin sensitivity
timeFrame: Baseline and 8 weeks of ADI-PEG20 or placebo
Secondary outcomes:
measure: Change in oral glucose tolerance
timeFrame: Baseline and 4 weeks of ADI-PEG20 or placebo
measure: Change in oral glucose tolerance
timeFrame: Baseline and 8 weeks of ADI-PEG20 or placebo
measure: Change in β-cell function
timeFrame: Baseline and 4 weeks of ADI-PEG20 or placebo
measure: Change in β-cell function
timeFrame: Baseline and 8 weeks of ADI-PEG20 or placebo
measure: Change in resting energy expenditure
timeFrame: Baseline and 8 weeks of ADI-PEG20 or placebo
measure: Change in muscle mitochondrial respiration
timeFrame: Baseline and 8 weeks of ADI-PEG20 or placebo
measure: Change in intrahepatic triglyceride content
timeFrame: Baseline and 8 weeks of ADI-PEG20 or placebo
Other outcomes:
measure: Change in the transcriptome in muscle
timeFrame: Baseline and 8 weeks of ADI-PEG20 or placebo
measure: Change in the transcriptome in adipose tissue
timeFrame: Baseline and 8 weeks of ADI-PEG20 or placebo
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Samuel Klein, MD
role: PRINCIPAL_INVESTIGATOR
References: