NCT03919617

Metabolic Pathways of GRA in Patients With Type 1 Diabetes

The Effects of a Glucagon Receptor Antagonist (GRA) on Non-Glucose Metabolic Pathways in Patients With Type 1 Diabetes (Pilot Study)

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 4 (actual)
• Sponsor: University of California, San Diego · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

A pilot study for individuals with Type 1 Diabetes who are willing to add a GRA (Glucagon Receptor Antagonist) to their current Diabetes treatment regimen. There will be 10 study visits over the course of approximately 8 weeks, with 4 weeks of once weekly, subcutaneous GRA (REMD-477) injection. Testing includes 2 MRI scans, 2 glucose challenges, and 2 insulin withdrawal challenges along with physical assessments and vitals.

Detailed description

This single-center, open label, multi-dose study is designed to elicit pilot data for a larger project. To accomplish the specific aims proposed, a single clinical trial will be conducted in which a maximum of 10 subjects with T1D, who are otherwise healthy, will be treated with REMD-477 for 4 weeks at a dose of 70mg (administered subcutaneously each week) with assessments done pre- and post-therapy. There is no comparator, nor is there any placebo in the study. In addition, there is no randomization, all subjects will receive the same 4 weeks of 70mg, once weekly dose of REMD-477. There will be 10 study visits as outlined below: 1. Screening - Complete medical history and physical exam, review of current medications, height/weight, vital signs, and fasting laboratory (blood and urine) tests. 2. Visit 1 - Participants that meet screening criteria will be provided deuterated (heavy) water to consume overnight. Participants will ingest heavy water (2H2O) overnight in three equal doses (total 3ml/kg/body water). Participants will also undergo an MRI to evaluate hepatic (liver) fat content as well as total body composition. 3. Visit 2 - Following Visit 1, participants will return to the clinic the next morning in the fasting state (8 hours) and after completing the heavy water consumption. Blood samples will be drawn for baseline amino acid levels as well as samples of serum, plasma, PBMCs, and extracted RNA stored for future metabolomics and genetic testing. Indirect calorimetry (IDC) will be performed to provide baseline resting energy expenditure (REE). Upon completion of IDC, participants will be given a 0.15 u/kg dose of rapid acting insulin and 15 minutes afterwards will ingest a 75g glucose and 25g fructose drink. Participants will then have samples collected over 6 hours to quantify isotope enrichment in plasma water as well as triglyceride isolated from VLDL. Repeat IDC will be performed 2 hours after consumption of the drink. 4. Visit 3 - Insulin withdrawal challenge and injection #1 of REMD-477. Participants will suspend insulin delivery and remove insulin pump. Blood sugars and ketones will be monitored for up to 6 hours. 5. Visit 4 - Injection #2 of REMD-477. 6. Visit 5 - Injection #3 of REMD-477. 7. Visit 6 - Injection #4 of REMD-477. 8. Visit 7 - Provide heavy water and complete MRI scan #2. 9. Visit 8 - Repeat all Visit 2 procedures. 10. Visit 9 - Repeat all Visit 3 procedures. 11. Visit 10 - Safety follow-up visit that includes physical exam, vitals, blood and urine sample collection.

Conditions

• Type 1 Diabetes Mellitus

Interventions

Type	Name	Description
DRUG	REMD-477	4-Week, open-label, once weekly subcutaneous injection with 70mg REMD-477.

Timeline

• Start date: 2019-07-01
• Primary completion: 2021-07-31
• Completion: 2022-05-31
• First posted: 2019-04-18
• Last updated: 2022-07-15

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study