The Role of Glucagon in Glucose Metabolism in Humans With and Without Bariatric Surgery
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: REMD-477 versus Placebo, Exogenous glucagon versus saline infusion.
- Who it may be relevant to
- Registry conditions: Non-Diabetic. Basic parameters: 18 years — 65 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Overview
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.
Detailed 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.
Interventions
- Drug REMD-477 versus Placebo
Placebo versus glucagon receptor antagonist using a human monoclonal antibody with a high level of antagonistic effect against human glucagon receptor. - Other Exogenous glucagon versus saline infusion
The effect of increased glucagon concentrations in plasma on glucose metabolism during glucose clamp will be studied.
Primary outcome measures
- Glycemc response to meal ingestion [Time frame: 0 to 240 minutes]
- Endogenous glucose production (EGP) during clamp studies [Time frame: 0 to 240 minutes]
Secondary outcome measures (3)
- Prandial glucose kinetics [Time frame: Baseline to 240 minutes]
- Plasma GLP-1, GIP, insulin and glucagon concentrations [Time frame: 0 to 240 minutes]
- Glucose clearance and insulin and glucagon concentrations during clamp studies [Time frame: 0 to 240 minutes]
Eligibility criteria
Inclusion criteria
- Provision of signed and dated informed consent form from participant.
- Male or female, ≤65 and ≥18 years old
- 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
- HbA1c ≤6%
- Willing to adhere to the study intervention regimen
- Female subjects of childbearing potential must have a negative pregnancy test at screening and all the study visits, and must not be lactating
- 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
- Diabetes
- Pregnancy/lactation
- Hgb <11
- Current GI obstruction or chronic diarrhea
- Subjects who are not within the age range of 18- 65 years.
- Evidence of active cardiorespiratory, hepatic, gastrointestinal or renal disease.
- History of allergy to the administered drugs.
- 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.
- Substance dependence or history of alcohol abuse and/or excess alcohol intake
- Patients on ketogenic diet
- Prisoners or institutionalized individuals
- AST (SGOT) > 3 times upper limit of normal
- ALT (SGPT) > 3 times upper limit of normal
- History of clinical hypoglycemia documents based on Whipples' triad (ONLY for Aim 2)
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: Yes
Study design
- Allocation
- Non-randomized
- Model
- Sequential
- Masking
- Single blind
- Primary purpose
- Other
Study locations
United States · 2 centers
- Texas Diabetes Institute - University Health System — San Antonio
- University of Texas San Antonio — San Antonio
Identifiers
NCT: NCT07212868 · STUDY00001597 · R01DK141843