NCT01434901

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
50

participants targeted

Target at P50-P75 for phase_1 type-2-diabetes-mellitus

Timeline
Completed

Started Aug 2011

Longer than P75 for phase_1 type-2-diabetes-mellitus

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 10, 2011

Completed
5 days until next milestone

Study Start

First participant enrolled

August 15, 2011

Completed
1 month until next milestone

First Posted

Study publicly available on registry

September 15, 2011

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 7, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 7, 2014

Completed
Last Updated

May 8, 2018

Status Verified

May 1, 2018

Enrollment Period

2.9 years

First QC Date

August 10, 2011

Last Update Submit

May 7, 2018

Conditions

Type 2 Diabetes Mellitus

Keywords

DiabetesBlood SugarXenin-25GIPMuscarinic

Outcome Measures

Primary Outcomes (1)

  • 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.

    3 years

Study Arms (3)

Normal Glucose Tolerance

EXPERIMENTAL

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

Drug: PlaceboDrug: Bethanechol (25 mg)Drug: Bethanechol (50 mg)Drug: Bethanechol (100 mg)

Impaired Glucose Tolerance

EXPERIMENTAL

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

Drug: PlaceboDrug: Bethanechol (25 mg)Drug: Bethanechol (50 mg)Drug: Bethanechol (100 mg)

Type 2 Diabetes Mellitus

EXPERIMENTAL

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: PlaceboDrug: Bethanechol (25 mg)Drug: Bethanechol (50 mg)Drug: Bethanechol (100 mg)

Interventions

PlaceboDRUG

A placebo will be taken by mouth 1 hour before ingestion of a mixed meal.

Impaired Glucose ToleranceNormal Glucose ToleranceType 2 Diabetes Mellitus
Bethanechol (25 mg)DRUG

25 mg of Bethanechol will be taken by mouth 1 hour before ingestion of a mixed meal

Impaired Glucose ToleranceNormal Glucose ToleranceType 2 Diabetes Mellitus
Bethanechol (50 mg)DRUG

50 mg of Bethanechol will be taken by mouth 1 hour before ingestion of a mixed meal

Impaired Glucose ToleranceNormal Glucose ToleranceType 2 Diabetes Mellitus
Bethanechol (100 mg)DRUG

100 mg of Bethanechol will be taken by mouth 1 hour before ingestion of a mixed meal

Impaired Glucose ToleranceNormal Glucose ToleranceType 2 Diabetes Mellitus

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • \<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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63131, United States

Location

Related Publications (1)

  • 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.

    PMID: 27304975RESULT

MeSH Terms

Conditions

Diabetes Mellitus, Type 2Diabetes Mellitus

Interventions

Bethanechol

Condition Hierarchy (Ancestors)

Glucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System Diseases

Intervention Hierarchy (Ancestors)

Bethanechol CompoundsTrimethyl Ammonium CompoundsQuaternary Ammonium CompoundsAminesOrganic ChemicalsCarbamatesAcids, AcyclicCarboxylic AcidsOnium Compounds

Study Officials

  • Burton M Wice, PhD

    Washington University School of Medicine

    PRINCIPAL INVESTIGATOR

  • Dominic Reeds, MD

    Washington University School of Medicine

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
SINGLE
Who Masked
PARTICIPANT
Purpose
BASIC SCIENCE
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 10, 2011

First Posted

September 15, 2011

Study Start

August 15, 2011

Primary Completion

July 7, 2014

Study Completion

July 7, 2014

Last Updated

May 8, 2018

Record last verified: 2018-05

Locations

US(1)