The Effects of Bethanechol on Glucose Homeostasis

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT01434901
First received: August 10, 2011
Last updated: July 21, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Placebo
Drug: Bethanechol (25 mg)
Drug: Bethanechol (50 mg)
Drug: Bethanechol (100 mg)
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Subject)
Primary Purpose: Basic Science
Official Title: The Effects of Bethanechol, a Muscarinic Agonist, on Plasma Insulin, Glucagon, and Glucose Levels in Humans With and Without Type 2 Diabetes Mellitus

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • The effects of Bethanechol on insulin secretion rates [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 40
Study Start Date: May 2011
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01434901

Locations
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63131
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: Burton M Wice, PhD Washington University School of Medicine
Principal Investigator: Dominic Reeds, MD Washington University School of Medicine
  More Information

No publications provided

Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT01434901     History of Changes
Other Study ID Numbers: 08-0861C, 1R01DK088126-01
Study First Received: August 10, 2011
Last Updated: July 21, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Washington University School of Medicine:
Diabetes
Blood Sugar
Xenin-25
GIP
Muscarinic

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Bethanechol
Muscarinic Agonists
Parasympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 27, 2014