Clinical trial NCT01799850: The Impact of Actos Treatment of Diabetes on Glucose Transporters in Muscle
Official title: The Impact of Actos Treatment of Diabetes on Glucose Transporters in Muscle
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetes Type 2
Keywords: muscle
glucose transporters
GLUT4
GLUT5
Actos
Lead sponsor: East Tennessee State University
Sponsor class: OTHER
Collaborators: name: Takeda Pharmaceuticals North America, Inc.
First posted: 2013-02-27
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* diabetes, type 2
* HbA1c less than 8.5

Exclusion Criteria:

* insulin therapy
* renal insufficiency
* clinically apparent coronary disease

Primary outcomes:
measure: change in muscle glucose transporter expression
timeFrame: post eight weeks treatment
Secondary outcomes:
Other outcomes:
Locations:
city: Johnson City
country: United States
facility: ETSU Quillen College of Medicine
state: Tennessee
Study officials:
affiliation: ETSU Quillen College of Medicine
name: Charles A Stuart, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Stuart CA, Howell ME, Yin D. Overexpression of GLUT5 in diabetic muscle is reversed by pioglitazone. Diabetes Care. 2007 Apr;30(4):925-31. doi: 10.2337/dc06-1788. Epub 2007 Jan 24.