Clinical trial NCT01434901: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type 2 Diabetes Mellitus
Keywords: Diabetes
Blood Sugar
Xenin-25
GIP
Muscarinic
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2011-09-15
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

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.

Primary outcomes:
measure: The effects of Bethanechol on insulin secretion rates
timeFrame: 3 years
Secondary outcomes:
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Burton M Wice, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Washington University School of Medicine
name: Dominic Reeds, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.