The Role of Glucagon in Glucose Metabolism in Humans With and Without Bariatric Surgery

The University of Texas System (UT)

Status and phase: Not yet enrolling; Phase 1

Conditions: Non-Diabetic

Treatments: Drug: REMD-477 versus Placebo; Other: Exogenous glucagon versus saline infusion

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT07212868

STUDY00001597

R01DK141843 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

The goal of this study is to understand the role of glucagon signal on glucose metabolism in individuals with and without bariatric surgery. The study is involved with measuring glucose metabolism with glucagon infusion and glucagon receptor blockade. We use an investigational drug called REMD 477. "Investigational" means that the has not yet been approved by the U.S. Food & Drug Administration (FDA). REMD-477 is a monoclonal antibody (an antibody made by cloning a unique white blood cell) that blocks the effect of glucagon.

Full description

Participants will be screened, and if eligible will be enrolled for metabolic studies for two separate aims. In aim 1, they undergo glucose clamp study with and without glucagon infusion.

In aim 2, they undergo 2-day meal studies with and without a single dose administration of investigational drug, REMD 477 using a small needle subcutaneously. During these studies glycemic profile will be evaluated using CGM (Continuous glucose monitoring). Participants will also have a blood draw for liver enzymes8 weeks after the administration of REMD 477.

Participants will spend up to 3- 6 months participating in any pair study.

Enrollment: 150 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Provision of signed and dated informed consent form from participant.
2. Male or female, ≤65 and ≥18 years old
3. Subjects with history of gastric bypass surgery and sleeve gastrectomy more than a year since surgery and non-surgical subjects without history of gastrointestinal (GI) surgery
4. HbA1c ≤6%
5. Willing to adhere to the study intervention regimen
6. Female subjects of childbearing potential must have a negative pregnancy test at screening and all the study visits, and must not be lactating
7. Females of childbearing potential who are sexually active with a nonsterilized male partner must use at least one highly effective method of contraception from screening and must agree to continue using such precautions during the study.It is strongly recommended for the male partner of a female subject to also use male condom plus spermicide throughout this period. Cessation of contraception after this point should be discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception.

Exclusion criteria

1. Diabetes
2. Pregnancy/lactation
3. Hgb <11
4. Current GI obstruction or chronic diarrhea
5. Subjects who are not within the age range of 18- 65 years.
6. Evidence of active cardiorespiratory, hepatic, gastrointestinal or renal disease.
7. History of allergy to the administered drugs.
8. History of, or any existing condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product, put the subject at risk, influence the subject's ability to participate or affect the interpretation of the results of the study and/or any subject unable or unwilling to follow study procedures.
9. Substance dependence or history of alcohol abuse and/or excess alcohol intake
10. Patients on ketogenic diet
11. Prisoners or institutionalized individuals
12. AST (SGOT) > 3 times upper limit of normal
13. ALT (SGPT) > 3 times upper limit of normal
14. History of clinical hypoglycemia documents based on Whipples' triad (ONLY for Aim 2)

Trial design

Primary purpose: Other

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: Single Blind

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150 participants in 2 patient groups

Mixed Meal study with and without glucagon receptor antagonist

Experimental group

Description:

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

Treatment:

Drug: REMD-477 versus Placebo

Pancreatic clamp (hypoglycemia and hyperglycemic) with and without glucagon infusion

Other group

Description:

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

Treatment:

Other: Exogenous glucagon versus saline infusion