Combination GRA and SGLT-2i Treatment in Type 1 Diabetes
Condition: Type 1 Diabetes
MeSH terms: 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 an SGLT-2i
      (Sodium-Glucose Cotransporter-2 Inhibitor) in combination with placebo or a GRA (Glucagon
      Receptor Antagonist) to their current diabetes treatment regimen. There will be 15 study
      visits over approximately 14 weeks in this cross-over study design. Treatment "A" consists of
      an SGLT-2i + GRA for 4 weeks and treatment "B" consists of an SGLT-2i + placebo for 4 weeks.
      All participants will complete both treatment "A" and treatment "B" with a 6-week washout
      period in between the treatments. Testing includes 3 insulin withdraw challenges, 3 muscle
      biopsies, 3 fat biopsies, 3 vascular ultrasounds along with blood collection and vitals.
    

Detailed description: 
      This is a single-center, randomized, double-blind, cross-over, multi-dose study 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 12 subjects with T1D, who are
      otherwise healthy, will be treated with an oral SGLT-2i (Sodium-Glucose Cotransporter-2
      Inhibitor), 10mg dapagliflozin taken daily in combination with a GRA (Glucagon Receptor
      Antagonist), 70mg REMD-477 subcutaneous injection once a week or placebo (subcutaneous
      injection to match the volume of REMD-477) once a week. There will be two treatments:
      Treatment "A" consists of an SGLT-2i + GRA for 4 weeks and Treatment "B" consists of an
      SGLT-2i + placebo for 4 weeks. Participants will be randomly assigned to either start with
      Treatment A or Treatment B for the first 4 weeks of treatment. After completing the first
      treatment group, participants will be washed off all study drug for 6 weeks. After the
      washout period, participants will complete 4 weeks of dosing with the opposite treatment they
      received during the first 4 weeks.

      There will be 15 study visits as outlined below:

        1. Screening - Complete medical history, physical exam, review current medications,
           height/weight, vital signs, ECG and fasting laboratory (blood and urine) tests.

        2. Baseline 1 - Complete vitals, weight, physical exam, fasting blood collection, download
           CGM data, collect insulin usage, complete measurements of blood vessels using EndoPat
           and ultrasound, complete diabetes questionnaires, and complete fat and muscle biopsies.

        3. Baseline 2 - Complete vitals, weight, fasting blood collection, insulin withdraw
           procedure and start first dose of study medications.

        4. Visit 4 - Complete vitals, weight, dose 2 of REMD-477/Placebo, review CGM data and
           insulin dosing.

        5. Visit 5 - Complete vitals, weight, dose 3 of REMD-477/Placebo, review CGM data and
           insulin dosing.

        6. Visit 6 - Complete vitals, weight, dose 4 of REMD-477/Placebo, review CGM data and
           insulin dosing.

        7. Repeat Measures 1 - Complete vitals, weight, physical exam, fasting blood collection,
           download CGM data, collect insulin usage, complete measurements of blood vessels using
           EndoPat and ultrasound, complete diabetes questionnaires, and complete fat and muscle
           biopsies.

        8. Repeat Measures 2 - Complete vitals, weight, fasting blood collection, insulin withdraw
           procedure and begin wash-out of study medications.

        9. Crossover Visit - Update medical history, complete physical exam, review of current
           medications, weight, vital signs, fasting laboratory (blood and urine) tests, collect
           insulin usage, download CGM data and start opposite doses of medication.

       10. Visit 10 - Complete vitals, weight, dose 2 of REMD-477/Placebo, review CGM data and
           insulin dosing.

       11. Visit 11 - Complete vitals, weight, dose 3 of REMD-477/Placebo, review CGM data and
           insulin dosing.

       12. Visit 12 - Complete vitals, weight, dose 4 of REMD-477/Placebo, review CGM data and
           insulin dosing.

       13. Final Measures 1 - Complete vitals, weight, physical exam, fasting blood collection,
           download CGM data, collect insulin usage, complete measurements of blood vessels using
           EndoPat and ultrasound, complete diabetes questionnaires, and complete fat and muscle
           biopsies.

       14. Final Measures 2 - Complete vitals, weight, fasting blood collection, insulin withdraw
           procedure and review CGM data/insulin dosing for return to pre-baseline diabetes
           treatment.

       15. Safety Follow-up - Complete vitals, physical exam, weight, and review CGM data/insulin
           dosing to verify diabetes treatment is stable.
    

Intervention name(s): Dapagliflozin 10 MG [Farxiga]; REMD-477; Placebo
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 4-Week, double-blind, once daily oral 10mg dapagliflozin; 4-Week, double-blind, once weekly subcutaneous injection with 35mg REMD-477 in 1mL solution.; 4-Week, double-blind, once weekly subcutaneous injection with placebo in 1mL solution.
Intervention MeSH terms: Dapagliflozin; Volagidemab
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Single-center, randomized, double-blind, cross-over, multi-dose study.
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Basic Science