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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат 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.
• Другое Exogenous glucagon versus saline infusion
  The effect of increased glucagon concentrations in plasma on glucose metabolism during glucose clamp will be studied.

Первичные конечные точки

• Glycemc response to meal ingestion [Срок оценки: 0 to 240 minutes]
• Endogenous glucose production (EGP) during clamp studies [Срок оценки: 0 to 240 minutes]

Вторичные конечные точки (3)

• Prandial glucose kinetics [Срок оценки: Baseline to 240 minutes]
• Plasma GLP-1, GIP, insulin and glucagon concentrations [Срок оценки: 0 to 240 minutes]
• Glucose clearance and insulin and glucagon concentrations during clamp studies [Срок оценки: 0 to 240 minutes]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Простое слепое

Основная цель

Другое

Центры проведения

США · 2 центра

• Texas Diabetes Institute - University Health System — San Antonio
• University of Texas San Antonio — San Antonio

Идентификаторы

NCT: NCT07212868 · STUDY00001597 · R01DK141843

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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