ObesityPhase 2NCT05829239
ADI-PEG20, Obesity and Prediabetes
A Phase 2 study testing ADI-PEG20 in people with Obesity and PreDiabetes, run by Washington University School of Medicine at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 22 years
- Conditions the study is for
- Obesity, PreDiabetes
- What is being tested?
- ADI-PEG20
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Apr 2024to 1 May 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 22 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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 locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: 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.
Read the 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.
- Conditions
- Obesity, PreDiabetes
- Being tested
- ADI-PEG20, Placebo
- Medical subject headings
- Obesity, Prediabetic State
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ADI-PEG20Biological
Intramuscular injection weekly for 8 weeks
PlaceboOther
Intramuscular injection weekly for 8 weeks
| Study group | Role | What they receive |
|---|---|---|
| ADI-PEG20 | Experimental | 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. Receives: Biological: ADI-PEG20 |
| Placebo | Placebo comparator | Will be weekly intramuscularly for 8-week Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in insulin sensitivity
Insulin sensitivity will be assessed by using the hyperinsulinemic-euglycemic clamp procedure
Measured: Baseline and 8 weeks of ADI-PEG20 or placebo
Secondary outcomes (7)
Change in oral glucose tolerance
Oral glucose tolerance will be assessed by measuring plasma glucose concentrations before and after ingesting 75 grams glucose
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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.
Measured: Baseline and 8 weeks of ADI-PEG20 or placebo
Change in intrahepatic triglyceride content
Intrahepatic triglyceride content will be assessed by magnetic resonance imagining (MRI)
Measured: Baseline and 8 weeks of ADI-PEG20 or placebo
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Apr 2023
- Study start1 Apr 2024
- Primary completion1 Apr 2024
- Study completion1 May 2024
Why it stopped: Unable to obtain study drug to be able to perform the study
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ObesityStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Single-center, randomized, double-blind, placebo-controlled study
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Children's Discovery Institute, Polaris Pharmaceuticals, Inc.
- Responsible party
- Sponsor
- Investigators
- Samuel Klein, MD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05829239
- Sponsor's protocol ID
- 202304058
- Status last verified
- Nov 2024
- First submitted
- 11 Nov 2022
- Last updated
- 7 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Trial Using ADI-PEG20 to Improve Insulin- and Energy Homeostasis in Adolescents With Obesity
- ClinicalTrials.gov ID
- NCT05829239
- Acronym / sponsor ID
- 202304058
- Conditions
- Obesity, PreDiabetes
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Unable to obtain study drug to be able to perform the study
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- Children's Discovery Institute, Polaris Pharmaceuticals, Inc.
- Study start
- 1 Apr 2024 (actual)
- Primary completion
- 1 Apr 2024 (actual)
- Study completion
- 1 May 2024 (actual)
- First posted
- 25 Apr 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Single-center, randomized, double-blind, placebo-controlled study
| Arm | Type | Receives |
|---|---|---|
| ADI-PEG20 | Experimental | Biological: ADI-PEG20ADI-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. |
| Placebo | Placebo comparator | Other: PlaceboWill be weekly intramuscularly for 8-week |
Who may qualify
- Ages
- 18 to 22 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ADI-PEG20Intramuscular injection weekly for 8 weeks | Biological | ADI-PEG20 |
| PlaceboIntramuscular injection weekly for 8 weeks | Other | Placebo |
Primary outcome
Change in insulin sensitivity
Time frame: Baseline and 8 weeks of ADI-PEG20 or placebo
Insulin sensitivity will be assessed by using the hyperinsulinemic-euglycemic clamp procedure
7 secondary outcomes
Change in oral glucose tolerance
Time frame: Baseline and 4 weeks of ADI-PEG20 or placebo
Change in oral glucose tolerance
Time frame: Baseline and 8 weeks of ADI-PEG20 or placebo
Change in β-cell function
Time frame: Baseline and 4 weeks of ADI-PEG20 or placebo
Change in β-cell function
Time frame: Baseline and 8 weeks of ADI-PEG20 or placebo
Change in resting energy expenditure
Time frame: Baseline and 8 weeks of ADI-PEG20 or placebo
Change in muscle mitochondrial respiration
Time frame: Baseline and 8 weeks of ADI-PEG20 or placebo
Change in intrahepatic triglyceride content
Time frame: Baseline and 8 weeks of ADI-PEG20 or placebo
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Nov 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Samuel Klein, MD principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ADI-PEG20 in people with Obesity and PreDiabetes, run by Washington University School of Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 7 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in insulin sensitivity (time frame: Baseline and 8 weeks of ADI-PEG20 or placebo). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Nov 2024.