Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01951729
Other study ID # 08-0861E
Secondary ID
Status Completed
Phase Phase 1
First received
Last updated
Start date March 13, 2013
Est. completion date May 2015

Study information

Verified date May 2018
Source Washington University School of Medicine
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

Glucose-dependent insulinotropic polypeptide (GIP) is a hormone produced in the intestine. It is released immediately after meal ingestion and increases insulin release. This, in turn, helps reduce blood glucose levels. This circuit does not work properly in humans with type 2 diabetes mellitus (T2DM).

We have previously shown that a peptide called xenin-25 can amplify the effects of GIP on insulin secretion in humans. However, xenin-25 no longer does this when humans develop T2DM. Thus, it is important to understand how xenin-25 works in humans without T2DM so we know why it does not work in humans with T2DM.

Acetylcholine is molecule produced by specific types of nerves. The effects of acetylcholine can be blocked by a drug called atropine. We have previously shown in mice that atropine prevents the ability of xenin-25 to increase the effects of GIP on insulin release. The purpose of this clinical trial is to determine if atropine also blocks the effects of xenin-25 in humans without T2DM. If it does, then impaired acetylcholine signaling may be one of the reasons humans develop T2DM and it could be possible to develop drugs that bypass this defect and increase insulin release in humans with T2DM.


Description:

Glucose-dependent insulinotropic polypeptide (GIP) is a hormone produced in the intestine. It is released immediately after meal ingestion and increases insulin release. This, in turn, helps reduce blood glucose levels. This circuit does not work properly in humans with type 2 diabetes mellitus (T2DM).

We have previously shown that a peptide called xenin-25 can amplify the effects of GIP on insulin secretion in humans. However, xenin-25 no longer does this when humans develop T2DM. Thus, it is important to understand how xenin-25 works in humans without T2DM so we know why it does not work in humans with T2DM.

Acetylcholine is molecule produced by specific types of nerves. The effects of acetylcholine can be blocked by a drug called atropine. We have previously shown in mice that atropine prevents the ability of xenin-25 to increase the effects of GIP on insulin release. The purpose of this clinical trial is to determine if atropine also blocks the effects of xenin-25 in humans without T2DM. If it does, then impaired acetylcholine signaling may be one of the reasons humans develop T2DM and it may be possible to develop drugs that bypass this defect and increase insulin release in humans with T2DM.

To conduct this study, we will enroll humans with pre-diabetes since they respond very well to xenin-25. Potential subjects will first be checked to see if they do have pre-diabetes and also to verify that they can safely participate in the study. Once enrolled, subjects will come for 8 different visits, each separated by about 3 weeks. On each visit, the subject will be given an intravenous infusion of glucose such that blood glucose levels slowly increase over a 4 hour period. On separate occasions, the participant will also receive an infusion GIP alone, xenin-25 alone, GIP plus xenin-25, or placebo. Each of these 4 infusions will be conducted with and without an infusion of atropine (thus- the 8 visits). Blood glucose and insulin levels, as well as a host of other hormones, will be measured during each of the study visits. A comparison of the results will tell us if the effects of xenin-25 on insulin release are mediated by acetylcholine in humans.


Recruitment information / eligibility

Status Completed
Enrollment 15
Est. completion date May 2015
Est. primary completion date May 2015
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 18 Years to 65 Years
Eligibility Inclusion Criteria:

- Individuals must be able to consent for their own participation (no mental impairment affecting cognition or willingness to follow study instructions).

- Otherwise healthy volunteers that have borderline diabetes or impaired glucose tolerance.

- Women of childbearing potential must be currently taking/using an acceptable method of birth control. 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.

- Willingness to complete all required visits.

Exclusion Criteria:

- Lacks cognitive ability to sign the consent or follow the study directions.

- Women unwilling to use an acceptable method of contraception during the course of the study, or who are currently breast-feeding.

- Volunteers with a history of Acute Pancreatitis.

- Volunteers with a history of cancer (except for skin cancer).

- Volunteer with a history of Chronic Pancreatitis and/or risk factors for chronic pancreatitis including hypertriglyceridemia, hypercalcemia and/or the presence of gallstones.

- Volunteers with a history of gastrointestinal disorders, particularly related to gastric motility/emptying such as gastric bypass

- Subjects taking medications known to affect glucose tolerance.

- Anemia

- Significant systemic illness including heart, kidney, inflammatory, liver, or malignant disease requiring medications.

- Narrow-angle glaucoma

- Obstructive uropathy including benign prostatic hypertrophy, pyloric stenosis, myasthenia gravis

- Asthma

- hyperthyroidism

- angina and cardiac arrhythmias including heart block

- Subjects unwilling to allow the use of human albumin in the preparation of the peptides.

- Unwillingness to allow blood glucose level adjustment (if needed) with IV insulin

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Control
Starting at 0 minutes, glucose infusion rates will be increased to 1, 2, 3, 4, 6, and 8 mg/kg/min every 40 minutes. The study is finished at 240 minutes. Starting at 0 minutes, an intravenous infusion of saline containing 1% human albumin will continue for 240 minutes.
Xenin-25 without atropine
Starting at 0 minutes, glucose infusion rates will be increased to 1, 2, 3, 4, 6, and 8 mg/kg/min every 40 minutes. The study is finished at 240 minutes. Following a priming dose from 0-10 minutes, xenin-25 (in saline containing 1% human albumin) will be administered at a constant dose of 4 pmoles/kg/min until 240 minutes.
GIP without atropine
Starting at 0 minutes, glucose infusion rates will be increased to 1, 2, 3, 4, 6, and 8 mg/kg/min every 40 minutes. The study is finished at 240 minutes. Following a priming dose from 0-10 minutes, GIP (in saline containing 1% human albumin) will be administered at a dose of 4 pmoles/kg/min until 240 minutes.
Placebo with atropine
Starting at 0 minutes, glucose infusion rates will be increased to 1, 2, 3, 4, 6, and 8 mg/kg/min every 40 minutes. The study is finished at 240 minutes. Following a priming dose from -30 to -28 minutes, atropine will be administered at a constant dose of 0.3 mg/m2/hour until 240 minutes.
Xenin-25 with atropine
Starting at 0 minutes, glucose infusion rates will be increased to 1, 2, 3, 4, 6, and 8 mg/kg/min every 40 minutes. The study is finished at 240 minutes. Following a priming dose from 0-10 minutes, xenin-25 (in saline containing 1% human albumin) will be administered at a dose of 4 pmoles/kg/min until 240 minutes. Following a priming dose from -30 to -28 minutes, atropine will be administered at a constant dose of 0.3 mg/m2/hour until 240 minutes.
GIP with atropine
Starting at 0 minutes, glucose infusion rates will be increased to 1, 2, 3, 4, 6, and 8 mg/kg/min every 40 minutes. The study is finished at 240 minutes. Following a priming dose from 0-10 minutes, GIP (iin saline containing 1% human albumin) will be administered at a dose of 4 pmoles/kg/min until 240 minutes. Following a priming dose from -30 to -28 minutes, atropine will be administered at a constant dose of 0.3 mg/m2/hour until 240 minutes.
GIP plus Xenin-25 without atropine
Starting at 0 minutes, glucose infusion rates will be increased to 1, 2, 3, 4, 6, and 8 mg/kg/min every 40 minutes. The study is finished at 240 minutes. Following a priming dose from 0-10 minutes, GIP and xenin-25 will each be administered at a dose of 4 pmoles/kg/min until 240 minutes.
GIP plus Xenin-25 with atropine
Starting at 0 minutes, glucose infusion rates will be increased to 1, 2, 3, 4, 6, and 8 mg/kg/min every 40 minutes. The study is finished at 240 minutes. Following a priming dose from 0-10 minutes, GIP and xenin-25 will each be administered at a dose of 4 pmoles/kg/min until 240 minutes. Following a priming dose from -30 to -28 minutes, atropine will be administered at a constant dose of 0.3 mg/m2/hour until 240 minutes.

Locations

Country Name City State
United States Washington University School of Medicine Saint Louis Missouri

Sponsors (2)

Lead Sponsor Collaborator
Washington University School of Medicine American Diabetes Association

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Other Plasma GIP levels during each treatment 3 years
Other Plasma xenin-25 levels during each treatment. 3 years
Primary Insulin secretion rates during each treatment. 3 years
Secondary Plasma glucose levels during each treatment. 3 years
Secondary Plasma glucagon levels during each treatment. 3 years
Secondary Plasma pancreatic polypeptide levels during each treatment. 3 years
See also
  Status Clinical Trial Phase
Completed NCT04082585 - Total Health Improvement Program Research Project
Enrolling by invitation NCT05367024 - Broccoli Effect on Glycated Haemoglobin (HbA1c) N/A
Completed NCT02933424 - Project Plant Protein: the P3 Study in Humans N/A
Withdrawn NCT02400450 - Designer Functional Foods on Parameters of Metabolic and Vascular in Prediabetes N/A
Completed NCT02656212 - Early Phase Pre-Clinical and Initial Clinical Research on Epicatechin (Part 2) Phase 1
Completed NCT02330276 - Early Phase Pre-Clinical and Initial Clinical Research on Epicatechin Phase 1
Completed NCT01488279 - Effect of Sitagliptin on Short-Term Metabolic Dysregulation of Oral Glucocorticoid Therapy N/A
Completed NCT00831129 - A Study for Pre-diabetic Patients With Cholesterol Lowering Drugs Phase 2/Phase 3
Completed NCT00536250 - Study to Investigate the Pathophysiology of Type 2 Diabetes in Youth N/A
Recruiting NCT05563090 - Investigating the Syndrome Differentiation of Diabetic and Pre-diabetic Using Digitalized TCM Diagnostic Tools
Active, not recruiting NCT04991142 - Models of Nutrition From Continuous Glucose Monitors
Completed NCT02759055 - Pre-Diabetes Cardiovascular (CV) Care (Pre-Diabetes Wizard) N/A
Completed NCT00775684 - Effect of Exenatide, Sitagliptin or Glimepiride on Functional ß -Cell Mass N/A
Completed NCT03695913 - Continuous Glucose Monitoring (CGM) With a Low Carbohydrate Diet to Reduce Weight in Patients With Pre-Diabetes N/A
Completed NCT04051008 - CTSI Pilot: Improving Adherence to Diabetic Diet N/A
Recruiting NCT04897945 - A Shared Decision Making Intervention for Diabetes Prevention in Women With a History of Gestational Diabetes Mellitus N/A
Not yet recruiting NCT04442451 - Mechanisms of Fatigability With Diabetes N/A
Not yet recruiting NCT05925933 - High Protein Diet on Transcriptomic, Metabolomics, Hepatic and Pancreatic Fat Anatomy and Physiology in Asian Indians With Pre-diabetes N/A
Active, not recruiting NCT05654051 - The SLIM LIVER Study Phase 2
Completed NCT02919397 - Motivational Instant Messaging and E-diabetes Prevention Programme for High Risk of Type 2 Diabetes N/A