Acute Metabolic Effects of LAF 237 in Type 2 Diabetics
|First Received Date ICMJE||September 28, 2005|
|Last Updated Date||January 3, 2006|
|Start Date ICMJE||November 2004|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
||Rate of appearance of endogenous glucose|
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||Complete list of historical versions of study NCT00230464 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Acute Metabolic Effects of LAF 237 in Type 2 Diabetics|
|Official Title ICMJE||A Double-Blind, Placebo-Controlled, Randomized, Crossover Study to Explore the Acute Effects of LAF 237 on the Rate of Appearance and Disappearance of Glucose During the Overnight Post-Absorptive Period in Type 2 Diabetics|
Incretin hormones (GIP and GLP-1) stimulate insulin release in a glucose dependant manner, hence are necessary for maintenance of normal glucose tolerance. Both GIP and GLP-1 are degraded and inactivated by DPP-4.
LAF 237 is an inhibitor of DPP-4 that has been shown to increase meal-stimulated levels of intact GLP-1 in animals and patients with T2DM..
The purpose of the current study is to explore the acute effects of LAF237 on the rate of appearance and disappearance of glucose in type 2 diabetics. Secondary objectives include the effect on FPG, insulin secretion rates, glucagon and FFA levels, and rate of glucose entry from the GI tract.
Study Design Double blind, placebo-controlled, randomized, two –period crossover study. Sixteen (16) both sexes diabetic patients will be enrolled and randomized to receive one of two treatment sequences (LAF-placebo or placebo-LAF).
At screening, patients will begin a weight maintaining diet containing 50% carbohydrates, 30% protein and 20% fat.
Within 7 days from screening patients will be scheduled for treatment 1. Patients will begin a 10-hour overnight fast on Day -1 at ~21h00. Patients will be admitted to GCRC next day. Fasting plasma glucose sample will be drawn and following this the patient will be served a standard breakfast containing 1/5 of their caloric allotment (50% carbohydrates, 30% protein and 20% fat). At noon patient will be fed a standard lunch containing 2/5 of their caloric allotment (50% carbohydrates, 30% protein and 20% fat). At 14h30 (-210) an infusion of 3-3H glucose will be started and continued until 08h00 next day (20 µCi x FPG/100 continuous, 0.20/min). At 17h30 (-30) patients will ingest 100 mg of LAF237 or placebo with 200 ml of water. At 18h00 (time zero) patients will be served a dinner (2/5 of their caloric allotment). The carbohydrates (glucose) in the meal will be labeled with 75 µCi of [1-14C]-glucose.
At -60, -50, -40, -35, -30, -20, -10, -5, and 0 minutes before dinner plasma samples for determination of glucose, insulin, C-peptide, glucagons, GLP-1, GIP, FFA, lactate, and amino acid concentrations and 3-3H glucose radioactivity will be drawn. Following dinner, further blood samples will be drawn every 15 minutes for 3.5 hours (18h00-21h30) and every 30 minutes for the next 10.5 hours (22h00-08h00 Day 2). Post dinner samples will be analyzed for the above parameter as well as for 14C glucose radioactivity. At 08h00 on Day 2, both catheters will be removed and the patients will be fed breakfast and then released from the site.
In addition to blood samples, urine from dinner time until 08h00 on Day 2 will be collected.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 3|
|Study Design ICMJE||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Primary Purpose: Treatment
|Condition ICMJE||Type 2 Diabetes Mellitus|
|Intervention ICMJE||Drug: LAF 237|
|Study Arm (s)||Not Provided|
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Completion Date||September 2005|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages||18 Years to 75 Years|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Location Countries ICMJE||United States|
|NCT Number ICMJE||NCT00230464|
|Other Study ID Numbers ICMJE||CLAF237A2346|
|Has Data Monitoring Committee||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||The University of Texas Health Science Center at San Antonio|
|Information Provided By||The University of Texas Health Science Center at San Antonio|
|Verification Date||September 2005|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP