The Effects of a GRA on Non-Glucose Metabolic Pathways in Patients With Type 1 Diabetes (Pilot Study)
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|ClinicalTrials.gov Identifier: NCT03919617|
Recruitment Status : Not yet recruiting
First Posted : April 18, 2019
Last Update Posted : April 18, 2019
|Condition or disease||Intervention/treatment||Phase|
|Type 1 Diabetes Mellitus||Drug: REMD-477||Phase 1 Phase 2|
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:
- Screening - Complete medical history and physical exam, review of current medications, height/weight, vital signs, and fasting laboratory (blood and urine) tests.
- 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.
- 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.
- 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.
- Visit 4 - Injection #2 of REMD-477.
- Visit 5 - Injection #3 of REMD-477.
- Visit 6 - Injection #4 of REMD-477.
- Visit 7 - Provide heavy water and complete MRI scan #2.
- Visit 8 - Repeat all Visit 2 procedures.
- Visit 9 - Repeat all Visit 3 procedures.
- Visit 10 - Safety follow-up visit that includes physical exam, vitals, blood and urine sample collection.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||10 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Single-center, open label, multi-dose study.|
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|Official Title:||The Effects of a Glucagon Receptor Antagonist (GRA) on Non-Glucose Metabolic Pathways in Patients With Type 1 Diabetes (Pilot Study)|
|Estimated Study Start Date :||April 26, 2019|
|Estimated Primary Completion Date :||December 1, 2019|
|Estimated Study Completion Date :||December 31, 2019|
|Experimental: Open-Label REMD-477||
4-Week, open-label, once weekly subcutaneous injection with 70mg REMD-477.
- Beta-hydoxybutyrate (BHB) Level Reduction [ Time Frame: 4-Weeks ]Participants treated with GRA therapy will have a clinically meaningful 20% reduction in peak BHB production as measured by the insulin withdrawal challenge.
- Rate of De Novo Lipogenesis (DNL) [ Time Frame: 4-Weeks ]Disrupted glucagon signaling by GRA will increase rates of DNL by 20% as measured by the glucose challenge and deuterated water ingestion.
- Rate of Hepatic Steatosis [ Time Frame: 4-Weeks ]Disrupted glucagon signaling by GRA will not induce changes in hepatic steatosis as measured by the glucose challenge and deuterated water ingestion.
- Rate of Resting Energy Expenditure (REE) [ Time Frame: 4-Weeks ]Disrupted glucagon signaling by GRA will reduce REE by 15% as measured by the glucose challenge and deuterated water ingestion.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03919617
|Contact: Todd Mayemail@example.com|