The Impact of Actos Treatment of Diabetes on Glucose Transporters in Muscle

Study Overview
=================
Brief Summary
-----------------
Subjects with type 2 diabetes will be treated with Actos or placebo for eight weeks and needle biopsies of muscle will quantify changes in any of seven different glucose transport proteins in muscle.

Detailed Description
-----------------
Twelve subjects with type 2 diabetes, with fair control on oral medication, will be recruited to participate in a randomized, double-blind, placebo-controlled study of the impact on muscle glucose transporter expression of the addition of the insulin-sensitizing agent, pioglitizone (Takeda Pharmaceuticals). Therapy with the active drug will be at 30 mg daily. The other oral medications will be adjusted downward if hypoglycemia occurs. Glycemic control will be monitored by at least twice daily home blood glucose monitoring, weekly telephone contacts, and follow-up visits to the ETSU/VAMC Clinical Research Unit (CRU) every two weeks. During the eight weeks of therapy, subjects will be instructed to maintain their weight and keep their dietary and exercise regimens unchanged. Muscle biopsies will be obtained before and at the end of eight weeks of therapy. Specimens will be assayed for GLUT1, GLUT3, GLUT4, GLUT5, GLUT8, GLUT11, and GLUT12 mRNA and protein content and the subcellular distribution of these proteins as described below. Peroxisome proliferator-activated receptor gamma (PPARgamma), a member of the ligand-activated nuclear hormone receptor superfamily (14), will be quantified in these specimens by immunoblot as described below. This study design involving a randomized, double-blinded, placebo-controlled treatment regimen is needed to control for confounding variables causing changes in glucose transporter expression that may be erroneously attributed to the drug. These potential variables include close contact with the diabetes management team resulting in improved compliance with diet, exercise, medication, and monitoring and thus better glycemic control, weight loss, or improved fitness.

Official Title
-----------------
The Impact of Actos Treatment of Diabetes on Glucose Transporters in Muscle

Conditions
-----------------
Diabetes Type 2

Intervention / Treatment
-----------------
* Drug: Pioglitazone
* Drug: placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: diabetes, type 2 HbA1c less than 8.5 Exclusion Criteria: insulin therapy renal insufficiency clinically apparent coronary disease

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Actos<br>Actos 30 mg daily | Drug: Pioglitazone<br>* pioglitazone 30 mg daily, pill, eight weeks, placebo randomly assigned<br>* Other names: Actos or placebo;|
| Placebo Comparator: placebo<br>double blind placebo controlled | Drug: placebo<br>* placebo assigned randomly, double blind<br>* Other names: sugar pill;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in muscle glucose transporter expression | immunoblots pre and post, placebo and Actos | post eight weeks treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
muscle, glucose transporters, GLUT4, GLUT5, Actos