GIP: Glucose-dependent Insulinotropic Peptide

Type 2 Diabetes Clinical Trial

Official title:

Effect of GIP / GIP Analog in Type 2 Diabetes After a Meal

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00239707
• Other study ID #: AG0056
• Status: Completed
• Phase: Phase 1
• First received: October 13, 2005
• Last updated: November 27, 2013
• Start date: February 2003
• Est. completion date: December 2006

Study information

• Verified date: November 2013
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to test the safety of glucose-dependent insulinotropic peptide (GIP)/GIP Analog on people with Type 2 Diabetes.

Description:

The small bowel makes a hormone called glucose-dependent insulinotropic peptide (GIP). It is released into the blood stream and goes to the pancreas. It works there with nutrients, especially glucose, in the digested food so that insulin is released in sufficient amounts from the pancreas. The insulin causes the nutrients from the food to be stored in the liver, fat and muscle until they are needed to provide energy. GIP also slows emptying of food from the stomach, which decreases the rate with which fats in food are broken down and stored. Once it is released into the blood, GIP is quickly broken down and becomes inactive. Individuals with type 2 diabetes do not make enough GIP and pharmacological doses of naturally occurring GIP do not increase insulin secretion in patients with type 2 diabetes. This study is testing a modified GIP (it had one amino acid difference from naturally occurring human GIP) that is not broken down as quickly in individuals with type 2 diabetes, to determine if it will improve insulin secretion, after eating, in patients with type 2 diabetes. The study will also compare its effects to that of naturally occurring, human GIP. Both human GIP and the modified GIP (GIP analog) are manufactured by peptide synthesis techniques (not extracted from human gut and not recombinant technology).

A screening visit will be performed including blood work, EKG and physical exam. If eligible, patients would be scheduled for three infusion visits 2 months apart, where they will receive a normal saline infusion on the first visit and GIP or GIP analog on the remaining visits. The infusion visits will begin approximately 6:45 a.m. and patients will have frequent blood sampling through an intravenous line over a period of 7 hours. An additional intravenous line will be placed for the infusion of either the normal saline, GIP or GIP analog over a period of 3 hours. Patients will be given a breakfast meal consisting of 550 calories (one egg, piece of toast with margarine, corn flakes 2% milk and a banana). They will be given 2 Extra-Strength Tylenol to determine time frame that food is emptied from stomach by measuring Tylenol levels in the blood. At the end of each study visit, patients will be given lunch, intravenous lines will be discontinued and they will be discharged to home.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: December 2006
• Est. primary completion date: December 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 18 years of age and older

• Healthy Type 2 Diabetics

• Agree to stay off glucosidases for 3 days prior to infusion visits (Examples:

Precose, Glyset)

• Agree to stay off Sulfonylureas 5 days prior to infusion visits (Examples: Glucotrol, Amaryl, glyburide, metformin

• Able to ingest 1000 mg Tylenol on study visits

• Able to consume study breakfast consisting of scrambled egg, white toast with margarine, corn flakes, 2% milk, banana at each infusion visit

• Female participants must have Hct > 36

• Male participant must have Hct > 38

• No kidney or liver disease per history and evidenced by blood and urine tests

• Physical Exam and EKG that do not contraindicate patient to be in the study

Exclusion Criteria:

• Taking the following medications: Insulin, or Thiazolidinediones, i.e. Avandia, Actos

• Pregnancy

• Steroid use within the past 3 months

• Recent infection, fever or chills

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

Drug:
• GIP
One-time 20 ng/kg/min infusion over 3 hours
• Modified GIP
One-time infusion over 3 hours; dose to maintain desired biological effect of below 140 mg/dl
• Normal Saline
one-time infusion over 3 hours

Locations

Country	Name	City	State
United States	National Institute on Aging, Clinical Research Branch	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Institute on Aging (NIA)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Elahi D, Andersen DK, Brown JC, Debas HT, Hershcopf RJ, Raizes GS, Tobin JD, Andres R. Pancreatic alpha- and beta-cell responses to GIP infusion in normal man. Am J Physiol. 1979 Aug;237(2):E185-91. — View Citation

Elahi D, McAloon-Dyke M, Fukagawa NK, Meneilly GS, Sclater AL, Minaker KL, Habener JF, Andersen DK. The insulinotropic actions of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (7-37) in normal and diabetic subjects. Regul Pept. 1994 Apr 14;51(1):63-74. — View Citation

Nauck MA, Heimesaat MM, Orskov C, Holst JJ, Ebert R, Creutzfeldt W. Preserved incretin activity of glucagon-like peptide 1 [7-36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus. J Clin Invest. 1993 Jan;91(1):301-7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	GIP, glucose, insulin measured frequently during infusions		baseline, 2 months, and 4 months	No
Secondary	GLP-1, ghrelin measured frequently during infusions		baseline, 2 months, and 4 months	No