Metabolic Pathways of GRA in Patients With Type 1 Diabetes
Condition: Type 1 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Study type: Interventional
Phase: Phase 1/Phase 2

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.
    

Intervention name(s): REMD-477
Intervention type(s): Drug
Intervention description(s): 4-Week, open-label, once weekly subcutaneous injection with 70mg REMD-477.
Intervention MeSH terms: Volagidemab
Intervention model: Single Group Assignment
Intervention model description: Single-center, open label, multi-dose study.
Masking: None (Open Label)
Primary purpose: Basic Science