Non-Diabetic
Conditions
Keywords
glucagon, glucose metabolism, bariatric surgery
Brief summary
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
DRUGREMD-477 versus Placebo
Placebo versus glucagon receptor antagonist using a human monoclonal antibody with a high level of antagonistic effect against human glucagon receptor.
OTHERExogenous glucagon versus saline infusion
The effect of increased glucagon concentrations in plasma on glucose metabolism during glucose clamp will be studied.
Sponsors
The University of Texas Health Science Center at San Antonio
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
SINGLE (Subject)
Masking description
Masking for participants
Intervention model description
Placebo controlled physiologic study
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Glycemc response to meal ingestion | 0 to 240 minutes | Changes in glucose response to meal ingestion occurred by administration of glucagon receptor antagonist (GRA). |
| Endogenous glucose production (EGP) during clamp studies | 0 to 240 minutes | Changes in EGP (measured by tracer technique) with and without glucagon infusion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Prandial glucose kinetics | Baseline to 240 minutes | Glucose flux with and without GRA administration |
| Plasma GLP-1, GIP, insulin and glucagon concentrations | 0 to 240 minutes | Changes in these outcomes following meal ingestion with and without GRA administration |
| Glucose clearance and insulin and glucagon concentrations during clamp studies | 0 to 240 minutes | Outcomes with and without glucagon infusion |
Countries
United States
Contacts
CONTACTMarzieh Salehi, MD, MS
CONTACTAndrea Hansis-Diarte, MPh
PRINCIPAL_INVESTIGATORMarzieh Salehi, MD, MS
The University of Texas Health Science Center at San Antonio
Outcome results
None listed