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The Effects of Bethanechol on Glucose Homeostasis

Primary Purpose

Type 2 Diabetes Mellitus

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Placebo
Bethanechol (25 mg)
Bethanechol (50 mg)
Bethanechol (100 mg)
Sponsored by
Washington University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Type 2 Diabetes Mellitus focused on measuring Diabetes, Blood Sugar, Xenin-25, GIP, Muscarinic

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • Washington University School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Normal Glucose Tolerance

Impaired Glucose Tolerance

Type 2 Diabetes Mellitus

Arm Description

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

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

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.

Outcomes

Primary Outcome Measures

The effects of Bethanechol on insulin secretion rates
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.

Secondary Outcome Measures

Full Information

First Posted
August 10, 2011
Last Updated
May 7, 2018
Sponsor
Washington University School of Medicine
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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1. Study Identification

Unique Protocol Identification Number
NCT01434901
Brief Title
The Effects of Bethanechol on Glucose Homeostasis
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2018
Overall Recruitment Status
Completed
Study Start Date
August 15, 2011 (Actual)
Primary Completion Date
July 7, 2014 (Actual)
Study Completion Date
July 7, 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Washington University School of Medicine
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes Mellitus
Keywords
Diabetes, Blood Sugar, Xenin-25, GIP, Muscarinic

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
Participant
Allocation
Non-Randomized
Enrollment
50 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Normal Glucose Tolerance
Arm Type
Experimental
Arm Description
Healthy individuals exhibiting plasma glucose levels less than 140mg/dl two hours after ingestion of 75-g of glucose.
Arm Title
Impaired Glucose Tolerance
Arm Type
Experimental
Arm Description
Healthy individuals exhibiting plasma glucose levels between 140 and 199 mg/dl two hours after ingestion of 75-g of glucose.
Arm Title
Type 2 Diabetes Mellitus
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
A placebo will be taken by mouth 1 hour before ingestion of a mixed meal.
Intervention Type
Drug
Intervention Name(s)
Bethanechol (25 mg)
Intervention Description
25 mg of Bethanechol will be taken by mouth 1 hour before ingestion of a mixed meal
Intervention Type
Drug
Intervention Name(s)
Bethanechol (50 mg)
Intervention Description
50 mg of Bethanechol will be taken by mouth 1 hour before ingestion of a mixed meal
Intervention Type
Drug
Intervention Name(s)
Bethanechol (100 mg)
Intervention Description
100 mg of Bethanechol will be taken by mouth 1 hour before ingestion of a mixed meal
Primary Outcome Measure Information:
Title
The effects of Bethanechol on insulin secretion rates
Description
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.
Time Frame
3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Burton M Wice, PhD
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Dominic Reeds, MD
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63131
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
27304975
Citation
Chowdhury S, Wang S, Dunai J, Kilpatrick R, Oestricker LZ, Wallendorf MJ, Patterson BW, Reeds DN, Wice BM. Hormonal Responses to Cholinergic Input Are Different in Humans with and without Type 2 Diabetes Mellitus. PLoS One. 2016 Jun 15;11(6):e0156852. doi: 10.1371/journal.pone.0156852. eCollection 2016.
Results Reference
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The Effects of Bethanechol on Glucose Homeostasis

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