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).
The Effects of Glucagon Antagonism on Insulin Sensitivity, Cardiovascular Risk, and Ketogenesis in Type 1 Diabetes
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.
Type 1 Diabetes, Type 1 Diabetes Mellitus, Volagidemab, REMD-477
You can join if…
Open to people ages 18-65
- Men and women between the ages of 18 and 65 years old, inclusive, at the time of screening;
- Females of non-child bearing potential must be ≥ 1 year post-menopausal or documented as being surgically sterile. Females of child bearing potential must agree to use two methods of contraception during the entire study and for an additional 3 months after the end of dosing with the investigational product;
- Male subjects must be willing to use clinically acceptable method of contraception during the entire study and for an additional 6 months after the end of the treatment period;
- Diagnosed with Type 1 diabetes based on clinical history or as defined by the current American Diabetes Association (ADA) criteria for > 5 years;
- Treatment with a stable insulin regimen for at least 8 weeks before screening with continuous subcutaneous insulin infusion (CSII) via an insulin pump;
- Currently using a Continuous Glucose Monitoring (CGM) system;
- HbA1c ≤ 8.5 % at screening;
- A minimum weight of 50kg;
- eGFR ≥ 60 mL/min/1.73m²
- . Able to provide written informed consent approved by an Institutional Review Board (IRB).
You CAN'T join if...
- History or evidence of clinically-significant disorder or condition that, in the opinion of the Investigator, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion;
- History of pancreatitis, medullary thyroid carcinoma and/or liver disease;
- Clinically significant diagnosis of anemia;
- Body Mass Index (BMI) < 18.5 kg/m2 and/or weight less than 50kg;
- Whole blood donation of 1 pint (500 mL) within 8 weeks prior to Screening. Donations of plasma, packed RBCs, platelets or quantities less than 500 mL are allowed at investigator discretion;
- Current or recent (within 1 month of screening) use of diabetes medications other than insulin;
- Women who are pregnant or lactating/breastfeeding;
- Unable or unwilling to follow the study protocol or who are non-compliant with screening appointments or study visits;
- Any other condition(s) that might reduce the chance of obtaining study data, or that might cause safety concerns, or that might compromise the ability to give truly informed consent.
- UC San Diego Altman Clinical & Translational Research Institute
accepting new patients
La Jolla California 92037 United States
Lead Scientist at UCSD
- Jeremy Pettus, MD
Associate Professor Of Clinical, Medicine, Vc-health Sciences-schools. Authored (or co-authored) 57 research publications
- accepting new patients
- Start Date
- Completion Date
- University of California, San Diego
- Phase 2 research study
- Study Type
- Expecting 30 study participants
- Last Updated
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