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Type 1 DiabetesPhase 1/2NCT04545411

Combination GRA and SGLT-2i Treatment in Type 1 Diabetes

A Phase 1/2 study testing Dapagliflozin 10 MG [Farxiga] and REMD-477 in people with Type 1 Diabetes, run by University of California, San Diego at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Type 1 Diabetes
What is being tested?
Dapagliflozin 10 MG [Farxiga] and REMD-477
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
12 participants
Where
1 siteUnited States
Study dates
22 Feb 2021to 31 Oct 2022
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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 (< 1u/kg per day) 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
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  • HbA1c ≤ 9 % 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).

Who cannot join

  • History of T2DM, maturity onset diabetes of the young (MODY), pancreatic surgery or chronic pancreatitis
  • Pancreas, pancreatic islet cells or renal transplant recipient
  • T1DM treatment with any other antihyperglycemic drug (e.g. metformin, alpha- glucosidase inhibitors, SGLT-2 inhibitors, pramlintide, inhaled insulin, pre-mixed insulins, etc.) within 30 days of run-in (visit 2)
  • Occurrence of severe hypoglycemia involving coma and/or seizure that required hospitalization or hypoglycemia-related treatment by an emergency physician or paramedic within 3 months prior to Visit 1 or Visit 2
  • Occurrence of DKA within 3 months prior to Visit 1 or Visit 2
  • Occurrence of symptomatic hypotension within 3 months prior to Visit 1 (Screen) or Visit 2
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  • Occurrence of multiple genital mycotic infections within 6 months prior to Visit 1 (Screen) or Visit 2
  • Acute coronary syndrome (non-STEMI, STEMI and unstable angina pectoris), stroke or transient ischemic attack (TIA) within 3 months prior to Visit 1 or Visit 2
  • Indication of liver disease, defined by serum levels of either alanine transaminase (ALT), aspartate transaminase (AST), or alkaline phosphatase above 3 x upper limit of normal (ULN) at Visit 1
  • Current signs and symptoms of anemia accompanied by a hemoglobin laboratory value at or below 10.0 g/dL at screening.
  • Active eating disorders such as bulimia or anorexia nervosa
  • 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;
  • Treatment with systemic corticosteroids within 30 days of run-in (visit 2), or planned initiation of such therapy at Visit 1 or Visit 2. Inhaled or topical use of corticosteroids (e.g. for asthma/chronic obstructive pulmonary disease) is acceptable.
  • Medical history of bladder cancer or treatment for any cancer in the last five years prior to Visit 1. Resected basal cell carcinoma considered cured is exempted.
  • Women who are pregnant, nursing, or who plan to become pregnant while in the trial
  • Intake of an investigational drug in another trial within 30 days prior to Visit 1
  • Patient not able to understand and comply with study requirements, based on Investigator's judgment
  • Any other clinical condition that, based on Investigator's judgment, would jeopardize patient safety during trial participation or would affect the study outcome (e.g. immunocompromised patients who might be at higher risk of developing genital or mycotic infections, patients with chronic viral infections etc.)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • UC San Diego Altman Clinical & Translational Research Institute

    La Jolla, California, 92037

Other trials in United States

About this study

Official title: Effect of Glucagon Receptor Antagonism on Ketogenesis in SGLT-2i Treated Subjects With T1D

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.

Read the 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.
Conditions
Type 1 Diabetes
Being tested
Dapagliflozin 10 MG [Farxiga], REMD-477, Placebo
Medical subject headings
Diabetes Mellitus, Type 1

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Dapagliflozin 10 MG [Farxiga]Drug

    4-Week, double-blind, once daily oral 10mg dapagliflozin

  • REMD-477Drug

    4-Week, double-blind, once weekly subcutaneous injection with 35mg REMD-477 in 1mL solution.

  • PlaceboDrug

    4-Week, double-blind, once weekly subcutaneous injection with placebo in 1mL solution.

Study groups in NCT04545411
Study groupRoleWhat they receive
Treatment AActive comparatorDaily, Oral,10mg dapagliflozin in combination with Weekly, Subcutaneous, 35mg in 1mL solution REMD-477
Receives: Drug: Dapagliflozin 10 MG [Farxiga]; Drug: REMD-477
Treatment BPlacebo comparatorDaily, Oral,10mg dapagliflozin in combination with Weekly, Subcutaneous, 1mL solution Placebo
Receives: Drug: Dapagliflozin 10 MG [Farxiga]; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in Beta-hydroxybutyrate (BHB) Level

    The change from baseline in peak BHB production as measured by the insulin withdrawal challenge.

    Measured: 4-Weeks

  2. Change in Glycemic Control

    The change from baseline glycemic control as measured by a 2-week average of CGM "time-in-range".

    Measured: 4-Weeks

  3. Change in Glycemic Control

    The change from baseline glycemic control as measured by HbA1c.

    Measured: 4-Weeks

  4. Change in Vascular Endothelial Function

    The change from baseline in vascular endothelial function as measured by flow mediated dilation (brachial artery diameter).

    Measured: 4-Weeks

  5. Change in Vascular Endothelial Function

    The change from baseline in vascular endothelial function as measured by reactive hyperemia-peripheral arterial tonometry (reactive hyperemia index).

    Measured: 4-Weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Sep 2020
  2. Study start22 Feb 2021
  3. Primary completion28 Feb 2022
  4. Study completion31 Oct 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Crossover
Model description
Single-center, randomized, double-blind, cross-over, multi-dose study.
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04545411
Sponsor's protocol ID
UC-MEDJP-03
Status last verified
Jan 2023
First submitted
28 Aug 2020
Last updated
23 Jan 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Dapagliflozin 10 MG [Farxiga] and REMD-477 in people with Type 1 Diabetes, run by University of California, San Diego at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Beta-hydroxybutyrate (BHB) Level (time frame: 4-Weeks). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04545411.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2023.

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