The Effects of Bethanechol on Glucose Homeostasis

Phase 1

Completed

• Conditions: Type 2 Diabetes Mellitus
• Interventions: Drug: Placebo; Drug: Bethanechol (25 mg); Drug: Bethanechol (50 mg); Drug: Bethanechol (100 mg)

• Registration Number: NCT01434901
• Lead Sponsor: 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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2011-08-10
• Study Start: 2011-08-15
• Study First Submitted QC: 2011-09-14
• Study First Posted: 2011-09-15
• Primary Completion: 2014-07-07
• Study Completion: 2014-07-07
• Status Verified: 2018-05
• Last Update Submitted: 2018-05-07
• Last Update Posted: 2018-05-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 50

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Impaired Glucose Tolerance	Bethanechol (50 mg)	Healthy individuals exhibiting plasma glucose levels between 140 and 199 mg/dl two hours after ingestion of 75-g of glucose.
Type 2 Diabetes Mellitus	Bethanechol (50 mg)	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.
Impaired Glucose Tolerance	Bethanechol (100 mg)	Healthy individuals exhibiting plasma glucose levels between 140 and 199 mg/dl two hours after ingestion of 75-g of glucose.
Normal Glucose Tolerance	Placebo	Healthy individuals exhibiting plasma glucose levels less than 140mg/dl two hours after ingestion of 75-g of glucose.
Normal Glucose Tolerance	Bethanechol (25 mg)	Healthy individuals exhibiting plasma glucose levels less than 140mg/dl two hours after ingestion of 75-g of glucose.
Normal Glucose Tolerance	Bethanechol (50 mg)	Healthy individuals exhibiting plasma glucose levels less than 140mg/dl two hours after ingestion of 75-g of glucose.
Normal Glucose Tolerance	Bethanechol (100 mg)	Healthy individuals exhibiting plasma glucose levels less than 140mg/dl two hours after ingestion of 75-g of glucose.
Impaired Glucose Tolerance	Placebo	Healthy individuals exhibiting plasma glucose levels between 140 and 199 mg/dl two hours after ingestion of 75-g of glucose.
Impaired Glucose Tolerance	Bethanechol (25 mg)	Healthy individuals exhibiting plasma glucose levels between 140 and 199 mg/dl two hours after ingestion of 75-g of glucose.
Type 2 Diabetes Mellitus	Placebo	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.
Type 2 Diabetes Mellitus	Bethanechol (25 mg)	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.
Type 2 Diabetes Mellitus	Bethanechol (100 mg)	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.

Primary Outcome Measures

Name	Time	Method
The effects of Bethanechol on insulin secretion rates	3 years	Insulin secretion rates (pmoles/min) will be calculated by deconvolution of plasma C-peptide levels. The investigators will then determine if post-prandial insulin secretion rates are greater following administration of Bethanechol compared to placebo.

Trial Locations

Locations (1)

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States