Glucagon for Glucose Metabolism

Not yet recruiting at 1 trial location

Overseen By Andrea Hansis-Diarte, MPh

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: The University of Texas Health Science Center at San Antonio

Disqualifiers: Diabetes, Pregnancy, GI obstruction, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how glucagon, a hormone that raises blood sugar, affects glucose metabolism in individuals who have undergone bariatric surgery and those who have not. Participants will receive an investigational drug, REMD-477, a glucagon blocker, to assess its impact on blood sugar levels. The trial consists of two parts: one involves a glucagon infusion, and the other tests the drug with a meal. Suitable candidates include those who had gastric bypass or sleeve gastrectomy over a year ago and do not have diabetes. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

Is there any evidence suggesting that REMD-477 is likely to be safe for humans?

Research has shown that REMD-477, a drug under study, demonstrated promising safety results in earlier tests. In studies involving individuals with type 1 diabetes, no serious side effects were reported, indicating the drug was generally well-tolerated. Another study involving individuals with type 2 diabetes found that the treatment not only improved blood sugar levels but was also well-received by patients.

These findings suggest that REMD-477 might be a safe option for managing blood sugar, although further research is needed to confirm this in larger groups. It is important to note that REMD-477 is still under study and has not yet received FDA approval. However, the initial safety data appears encouraging for those considering participation in a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about REMD-477 because it offers a novel approach to managing glucose metabolism by targeting the glucagon receptor. Unlike traditional treatments for glucose regulation, which often focus on insulin modulation, REMD-477 works by inhibiting the effects of glucagon, a hormone that raises blood sugar levels. This unique mechanism could provide better control of blood glucose levels, especially in conditions where glucagon plays a significant role, such as diabetes. Additionally, the treatment's potential for a more precise control of blood sugar levels without the need for constant monitoring could simplify management and improve quality of life for patients.

What evidence suggests that REMD-477 might be an effective treatment for glucose metabolism?

Research shows that REMD-477, a monoclonal antibody, can help manage blood sugar levels by blocking glucagon, a hormone that usually raises blood sugar levels. In this trial, participants will join two different study arms. One arm involves a pancreatic clamp study to compare the effect of glucagon infusion on glucose metabolism. The other arm conducts a mixed meal test with a glucagon receptor antagonist. Previous studies have shown that a single dose of REMD-477 reduced the need for insulin and improved blood sugar control without increasing the risk of low blood sugar. Another study found that similar treatments lowered blood sugar in both healthy individuals and those with type 2 diabetes. This suggests that REMD-477 could effectively manage blood sugar levels. ^{2 3 5 6 7}

Who Is on the Research Team?

Marzieh Salehi, MD, MS

Principal Investigator

The University of Texas Health Science Center at San Antonio

Are You a Good Fit for This Trial?

This trial is for non-diabetic individuals, with or without bariatric surgery. It aims to understand how glucagon affects glucose metabolism. Participants must meet certain health criteria not specified here.

Inclusion Criteria

Provision of signed and dated informed consent form from participant

HbA1c ≤6%

Willing to adhere to the study intervention regimen

Exclusion Criteria

Pregnancy/lactation

Hgb <11

History of allergy to the administered drugs

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Metabolic Studies - Aim 1

Participants undergo glucose clamp study with and without glucagon infusion

Up to 3-6 months

Metabolic Studies - Aim 2

Participants undergo 2-day meal studies with and without a single dose administration of investigational drug, REMD 477

Up to 3-6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including blood draw for liver enzymes

8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• REMD-477

Trial Overview The study tests the effects of REMD-477, a drug that blocks glucagon signals, against a placebo. Additionally, it compares natural glucagon infusion with saline (a saltwater solution) to see how each influences glucose levels.

How Is the Trial Designed?

Group I: Pancreatic clamp (hypoglycemia and hyperglycemic) with and without glucagon infusion Experimental Treatment 1 Intervention

A cross-over study to compare the effect of glucagon infusion on glucose metabolism measured during clamp studies

Group II: Mixed Meal study with and without glucagon receptor antagonist Experimental Treatment 1 Intervention

Mixed meal test conducted with a sequential design of receiving a single dose subcutaneous injection of glucagon receptor antagonist or placebo.

Who Is Running the Clinical Trial?

The University of Texas Health Science Center at San Antonio

Lead Sponsor

Trials

486

Recruited

92,500+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6181222/

Effect of a Glucagon Receptor Antibody (REMD-477) in ... We found a single dose of REMD-477 decreased insulin requirements and improved glycemic control, without an increase in hypoglycemia or adverse ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT07212868

The Role of Glucagon in Glucose Metabolism in Humans ... The goal of this study is to understand the role of glucagon signal on glucose metabolism in individuals with and without bariatric surgery. The ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2589004219301671

Antagonistic Glucagon Receptor Antibody Promotes α-Cell ... Short-term administration of the glucagon receptor antagonist LY2409021 lowers blood glucose in healthy people and in those with type 2 diabetes.

4. diabetesjournals.org diabetesjournals.org/care/article/39/7/1241/37350/Evaluation-of-Efficacy-and-Safety-of-the-Glucagon

Evaluation of Efficacy and Safety of the Glucagon Receptor ... In patients with type 2 diabetes, glucagon receptor antagonist treatment significantly lowered HbA1c and glucose levels with good overall ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9872851/

Glucagon receptor antagonist volagidemab in type 1 diabetes A phase 2 study testing glucagon receptor antagonist volagidemab as an adjunct to insulin therapy in patients was found to be safe and tolerable ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/29283470/

Effect of a glucagon receptor antibody (REMD-477) in type 1 ... No serious adverse events were reported. Glucagon receptor antagonism decreases insulin requirements and improves glycaemic control in patients with type 1 ...

7. cell.com cell.com/cell-reports/fulltext/S2211-1247(18)30114-1

Glucagon Receptor Antagonism Improves Glucose ... As expected, REMD 2.59 suppresses hepatic glucose production and improves glycemia. Surprisingly, it also enhances insulin action in both liver ...