Effects of GRA in Patients With Type 1

Type 1 Diabetes Clinical Trial

Official title: The Effects of Glucagon Antagonism on Insulin Sensitivity, Cardiovascular Risk, and Ketogenesis in Type 1 Diabetes

Status Active, not recruiting

Clinical Trial Summary

This study will examine the effects a Glucagon Receptor Antagonist (GRA), has on Insulin Sensitivity, Cardiovascular risks (CVD), and Ketone body formation in participants with Type 1 diabetes. The participants will complete blood tests, tests to measure energy expenditure, CVD risks, and insulin resistance. These tests will be performed prior to start of treatment and again after 12-weeks of treatment with the GRA (called REMD-477).

Clinical Trial Description

This single-center, double-blind, placebo-controlled, multi-dose study is designed to evaluate the effects of glucagon antagonism on insulin sensitivity, cardiovascular risk and ketogenesis in individuals with Type 1 Diabetes. To accomplish the specific aims proposed, a single clinical trial will be conducted in which a maximum of 30 subjects with T1D, who are otherwise healthy, will be treated with REMD-477 or matching placebo for up to 12 weeks at a dose of 70mg (administered subcutaneously each week) with assessments done pre- and post-therapy. Subjects will be randomized on a 1:1 basis to either the REMD-477 group or placebo group and all subjects will remain on their standard of care insulin therapy throughout the study. There will be 19 study visits as outlined below:

1. Screening - Complete consenting process, complete medical history and physical exam, review of current medications, collect height/weight, vital signs, and fasting laboratory (blood and urine) tests.

2. Baseline Visit 1 - Participants that meet screening criteria will complete cardiovascular tests including flow mediated dilation and EndoPat, complete vital signs, weight and laboratory tests for safety and CVD markers.

3. Baseline Visit 2 - Participants will complete a 2-Step Hyperinsulinemic/Euglycemic clamp with tracer, Indirect Calorimetry, muscle and adipose tissue biopsies.

4. Baseline Visit 3 - Insulin withdrawal challenge and injection #1 of REMD-477 or placebo. Participants will suspend insulin delivery and remove insulin pump. Blood sugars and ketones will be monitored for up to 8 hours.

5. Visit 4 - Injection #2 of REMD-477 or placebo and blood collection for safety labs.

6. Visit 5 - Injection #3 of REMD-477 or placebo.

7. Visit 6 - Injection #4 of REMD-477 or placebo and blood collection for safety labs.

8. Visit 7 - Injection #5 of REMD-477 or placebo.

9. Visit 8 - Injection #6 of REMD-477 or placebo and blood collection for safety labs.

10. Visit 9 - Injection #7 of REMD-477 or placebo.

11. Visit 10 - Injection #8 of REMD-477 or placebo and blood collection for safety labs.

12. Visit 11 - Injection #9 of REMD-477 or placebo.

13. Visit 12 - Injection #10 of REMD-477 or placebo and blood collection for safety labs.

14. Visit 13 - Injection #11 of REMD-477 or placebo.

15. Visit 14 - Injection #12 of REMD-477 or placebo and blood collection for safety labs.

16. Visit 15 - Repeat cardiovascular tests including flow mediated dilation and EndoPat, complete vital signs, weight and laboratory tests for safety and CVD markers.

17. Visit 16 - Repeat 2-Step Hyperinsulinemic/Euglycemic clamp with tracer, Indirect Calorimetry, muscle and adipose tissue biopsies.

18. Visit 17 - Repeat Insulin withdrawal challenge. Participants will suspend insulin delivery and remove insulin pump. Blood sugars and ketones will be monitored for up to 8 hours.

19. Visit 18 - Safety follow-up visit that includes physical exam, vitals, blood and urine sample collection. ;

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 1
• Type 1 Diabetes

• NCT number: NCT04779645
• Study type: Interventional
• Source: University of California, San Diego
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: July 31, 2021
• Completion date: March 31, 2025