ADI-PEG20, Obesity and Prediabetes

Obesity Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05829239
• Other study ID #: 202304058
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: July 2024
• Est. completion date: May 2026

Study information

• Verified date: April 2024
• Source: Washington University School of Medicine
• Contact: Nikki Plassmeyer, MA, RDN, LD
• Phone: 314-362-0590
• Email: nikkip[@]wustl.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Not yet recruiting
• Enrollment: 48
• Est. completion date: May 2026
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 22 Years

Eligibility

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

Related Conditions & MeSH terms

• Glucose Intolerance
• Obesity
• PreDiabetes
• Prediabetic State

Intervention

Biological:
• ADI-PEG20
Intramuscular injection weekly for 8 weeks

Other:
• Placebo
Intramuscular injection weekly for 8 weeks

Locations

Country	Name	City	State
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (3)

Lead Sponsor	Collaborator
Washington University School of Medicine	Children's Discovery Institute, Polaris Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in the transcriptome in muscle	The transcriptome will be evaluated by using RNA sequencing techniques	Baseline and 8 weeks of ADI-PEG20 or placebo
Other	Change in the transcriptome in adipose tissue	The transcriptome will be evaluated by using RNA sequencing techniques	Baseline and 8 weeks of ADI-PEG20 or placebo
Primary	Change in insulin sensitivity	Insulin sensitivity will be assessed by using the hyperinsulinemic-euglycemic clamp procedure	Baseline and 8 weeks of ADI-PEG20 or placebo
Secondary	Change in oral glucose tolerance	Oral glucose tolerance will be assessed by measuring plasma glucose concentrations before and after ingesting 75 grams glucose	Baseline and 4 weeks of ADI-PEG20 or placebo
Secondary	Change in oral glucose tolerance	Oral glucose tolerance will be assessed by measuring plasma glucose concentrations before and after ingesting 75 grams glucose	Baseline and 8 weeks of ADI-PEG20 or placebo
Secondary	Change in ß-cell function	ß-cell function will be assessed from a modified oral glucose tolerance test	Baseline and 4 weeks of ADI-PEG20 or placebo
Secondary	Change in ß-cell function	ß-cell function will be assessed from a modified oral glucose tolerance test	Baseline and 8 weeks of ADI-PEG20 or placebo
Secondary	Change in resting energy expenditure	Resting energy expenditure (in kcal/min) will be assessed by using indirect calorimetry	Baseline and 8 weeks of ADI-PEG20 or placebo
Secondary	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.	Baseline and 8 weeks of ADI-PEG20 or placebo
Secondary	Change in intrahepatic triglyceride content	Intrahepatic triglyceride content will be assessed by magnetic resonance imagining (MRI)	Baseline and 8 weeks of ADI-PEG20 or placebo