GIP: Glucose-dependent Insulinotropic Peptide

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

Detailed Description
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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.

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

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: GIP
* Drug: Modified GIP
* Drug: Normal Saline


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Infusion 1<br>Normal Saline | Drug: GIP<br>* One-time 20 ng/kg/min infusion over 3 hours<br>* Other names: Glucose dependent insulinotropic peptide;|
| Placebo Comparator: Infusion 2<br>GIP or modified GIP | Drug: Modified GIP<br>* One-time infusion over 3 hours; dose to maintain desired biological effect of below 140 mg/dl<br>* Other names: GIP analog;|
| Placebo Comparator: Infusion 3<br>GIP or modified GIP, opposite of Infusion 2 | Drug: Normal Saline<br>* one-time infusion over 3 hours<br>* Other names: Saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GIP, glucose, insulin measured frequently during infusions |  | baseline, 2 months, and 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GLP-1, ghrelin measured frequently during infusions |  | baseline, 2 months, and 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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insulin sensitivity, blood sugar