The Effects of Bethanechol on Glucose Homeostasis

May 7, 2018 updated by: Washington University School of Medicine

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

50

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Missouri
      • Saint Louis, Missouri, United States, 63131
        • Washington University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Normal Glucose Tolerance
Healthy individuals exhibiting plasma glucose levels less than 140mg/dl two hours after ingestion of 75-g of glucose.
Drug: Placebo
A placebo will be taken by mouth 1 hour before ingestion of a mixed meal.
Drug: Bethanechol (25 mg)
25 mg of Bethanechol will be taken by mouth 1 hour before ingestion of a mixed meal
Drug: Bethanechol (50 mg)
50 mg of Bethanechol will be taken by mouth 1 hour before ingestion of a mixed meal
Drug: Bethanechol (100 mg)
100 mg of Bethanechol will be taken by mouth 1 hour before ingestion of a mixed meal
Experimental: Impaired Glucose Tolerance
Healthy individuals exhibiting plasma glucose levels between 140 and 199 mg/dl two hours after ingestion of 75-g of glucose.
Drug: Placebo
A placebo will be taken by mouth 1 hour before ingestion of a mixed meal.
Drug: Bethanechol (25 mg)
25 mg of Bethanechol will be taken by mouth 1 hour before ingestion of a mixed meal
Drug: Bethanechol (50 mg)
50 mg of Bethanechol will be taken by mouth 1 hour before ingestion of a mixed meal
Drug: Bethanechol (100 mg)
100 mg of Bethanechol will be taken by mouth 1 hour before ingestion of a mixed meal
Experimental: Type 2 Diabetes Mellitus
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.
Drug: Placebo
A placebo will be taken by mouth 1 hour before ingestion of a mixed meal.
Drug: Bethanechol (25 mg)
25 mg of Bethanechol will be taken by mouth 1 hour before ingestion of a mixed meal
Drug: Bethanechol (50 mg)
50 mg of Bethanechol will be taken by mouth 1 hour before ingestion of a mixed meal
Drug: Bethanechol (100 mg)
100 mg of Bethanechol will be taken by mouth 1 hour before ingestion of a mixed meal

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The effects of Bethanechol on insulin secretion rates
Time Frame: 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.
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Washington University School of Medicine

Collaborators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 15, 2011

Primary Completion (Actual)

July 7, 2014

Study Completion (Actual)

July 7, 2014

Study Registration Dates

First Submitted

August 10, 2011

First Submitted That Met QC Criteria

September 14, 2011

First Posted (Estimate)

September 15, 2011

Study Record Updates

Last Update Posted (Actual)

May 8, 2018

Last Update Submitted That Met QC Criteria

May 7, 2018

Last Verified

May 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 08-0861C
  • 1R01DK088126-01 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Type 2 Diabetes Mellitus

Clinical Trials on Placebo

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Georgia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe