The Effects of Bethanechol on Glucose Homeostasis

The Effects of Bethanechol, a Muscarinic Agonist, on Plasma Insulin, Glucagon, and Glucose Levels in Humans With and Without Type 2 Diabetes Mellitus

Sponsors

Lead Sponsor: Washington University School of Medicine

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

Source Washington University School of Medicine
Brief Summary

Xenin-25 and glucose-dependent insulinotropic polypeptide (GIP) are hormones produced in the intestine that are released into the blood immediately after ingestion of a meal. Together, these 2 hormones increase insulin release and reduce blood glucose levels. Xenin-25 works by increasing acetylcholine release in pancreatic islets. This study will determine if a Bethanechol, a drug that is similar to acetylcholine, also increases insulin release and reduces blood glucose levels after ingestion of a mixed meal.

Detailed Description

Each eligible participant will be administered an oral glucose tolerance test (OGTT) so he/she can be assigned to the group with normal glucose tolerance (NGT), impaired glucose tolerance (IGT) which is between normal and diabetic, or type 2 diabetes mellitus (T2DM). Each study subject will then be administered a meal tolerance test (MTT) on 4 separate occasions. For the MTT, a liquid meal (Boost Plus) will be ingested following an overnight fast. A placebo or Bethanechol (25 mg, 50 mg, or 100 mg) will taken by mouth 1 hour before ingestion of the meal. Blood samples will be collected before and during the MTT for the measurement of glucose, insulin, C-peptide, and glucagon levels.

Overall Status Completed
Start Date 2011-08-15
Completion Date 2014-07-07
Primary Completion Date 2014-07-07
Phase Phase 1
Study Type Interventional
Primary Outcome
Measure Time Frame
The effects of Bethanechol on insulin secretion rates 3 years
Enrollment 50
Condition
Intervention

Intervention Type: Drug

Intervention Name: Placebo

Description: A placebo will be taken by mouth 1 hour before ingestion of a mixed meal.

Intervention Type: Drug

Intervention Name: Bethanechol (25 mg)

Description: 25 mg of Bethanechol will be taken by mouth 1 hour before ingestion of a mixed meal

Intervention Type: Drug

Intervention Name: Bethanechol (50 mg)

Description: 50 mg of Bethanechol will be taken by mouth 1 hour before ingestion of a mixed meal

Intervention Type: Drug

Intervention Name: Bethanechol (100 mg)

Description: 100 mg of Bethanechol will be taken by mouth 1 hour before ingestion of a mixed meal

Eligibility

Criteria:

Inclusion Criteria: - Ages 18-65. No minors will be studied. - Individuals must be able to consent for their own participation (no mental impairment affecting cognition or willingness to follow study instructions). - Healthy volunteers with no clinical evidence of T2DM (see below). - Otherwise healthy volunteers that have impaired glucose tolerance (see below). - Otherwise healthy volunteers with Diet Controlled T2DM (see below). - Otherwise healthy volunteers with T2DM that take oral agents only and if the subject's pre-existing oral anti-diabetic agents can be safely discontinued for 48 hours prior to Oral Glucose Tolerance Test. - Otherwise healthy volunteers with T2DM who do not use insulin for blood glucose control. - Persons with HbA1c ≤ 9%. - Women of childbearing potential must be currently taking/using a method of birth control that is acceptable to the investigators. A pregnancy test will be done at the beginning of each visit. Any woman with a positive pregnancy test will be removed from the study. Exclusion Criteria: - <18years of age or >65 years of age - Lacks cognitive ability to sign the consent &/or follow the study directions for themselves - Women unwilling to comply with using an acceptable method of contraception during the course of the study, or who are currently breast-feeding. - Any subject whose screening HbA1c is >9.0% - Type 2 diabetes requiring the use of supplemental insulin @ home - Volunteers with a history of Acute Pancreatitis - Volunteer with a history of Chronic Pancreatitis and/or risk factors for chronic pancreatitis including hypertriglyceridemia (triglycerides >400mg/ml) hypercalcemia (blood calcium level >11.md/dl) and/or the presence of gallstones. - Volunteers with a history of gastrointestinal disorders, particularly related to gastric motility/emptying such as gastric bypass, documented gastro-paresis in diabetic volunteers. - Volunteers with a history of cancer. Exception: skin cancer. - Diabetics that have the potential to have a low blood sugar without them being aware that their blood sugar is low (hypoglycemia unawareness). - Known heart, kidney. liver or pancreatic disease requiring medications. - Unwillingness to allow blood glucose level adjustment (if needed) with IV insulin. - Subjects with hyperthyroidism, coronary artery disease, peptic ulcer, asthma, chronic bronchitis, or COPD.

Gender:

All

Minimum Age:

18 Years

Maximum Age:

65 Years

Healthy Volunteers:

Accepts Healthy Volunteers

Overall Official
Location
Facility: Washington University School of Medicine
Location Countries

United States

Verification Date

2018-05-01

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 3
Arm Group

Label: Normal Glucose Tolerance

Type: Experimental

Description: Healthy individuals exhibiting plasma glucose levels less than 140mg/dl two hours after ingestion of 75-g of glucose.

Label: Impaired Glucose Tolerance

Type: Experimental

Description: Healthy individuals exhibiting plasma glucose levels between 140 and 199 mg/dl two hours after ingestion of 75-g of glucose.

Label: Type 2 Diabetes Mellitus

Type: Experimental

Description: Healthy individuals exhibiting plasma glucose levels greater than 150 mg/dL under fasting conditions OR greater than 199 mg/dl two hours after ingestion of 75-g of glucose.

Study Design Info

Allocation: Non-Randomized

Intervention Model: Crossover Assignment

Primary Purpose: Basic Science

Masking: Single (Participant)

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