"TAKE TIME" Pioglitazone Reverses Defects in Mitochondrial Biogenesis in Patients With T2DM
This study is designed to look at the effect of Pioglitazone treatment on the body's ability to burn food in order to produce energy.
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||Pioglitazone Reverses Defects in Mitochondrial Biogenesis in Patients With T2DM|
- Change in skeletal muscle mitochondrial number (electron microscopy + qPCR of mtDNA) and mitochondrial gene expression in T2DM patients treated with pioglitazone (vs. placebo) [ Time Frame: baseline and after intervention ] [ Designated as safety issue: No ]
- insulin sensitivity for insulin suppression of free fatty acid and glucose disposal [ Time Frame: baseline and after intervention ] [ Designated as safety issue: No ]
- electron transport chain activity; mitochondrial content by MRS (ATP max) [ Time Frame: baseline and after intervention ] [ Designated as safety issue: No ]
- intra hepatic and intra myocellular lipid by MRS; mitochondrial content by MRS (ATP max) post weight loss period [ Time Frame: baseline ,after treatment and after weight loss ] [ Designated as safety issue: No ]
|Study Start Date:||November 2006|
|Study Completion Date:||December 2007|
|Primary Completion Date:||December 2007 (Final data collection date for primary outcome measure)|
|No Intervention: 1|
During the double-blind, 12 weeks treatment period, subjects will self-administer study medication (pioglitazone or equivalent volume of placebo) 30 mg/day each morning. The dose of pioglitazone will be increased to 45 mg/day after 4 weeks if the fasting plasma glucose is higher than 100mg/dl or the HbA1C is higher than 7%. This dose has proven tolerability, safety and efficacy for type 2 diabetes and has previously been used at the Pennington Center in studies on pioglitazone.
Other Name: TZD
Skeletal muscle mitochondrial defects are a sine qua non of insulin resistance in patients with T2DM. Pioglitazone decreases free fatty acid levels and restores mitochondria number in adipose tissue whereas high fat diet and lipid infusion decreases genes involved in mitochondrial biogenesis. Increased lipid flux from diet or adipose tissue into skeletal muscle might be the cause of decreased mitochondrial biogenesis. The purpose of this study is to determine if 22 weeks treatment with Pioglitazone can increase mitochondrial biogenesis in muscle in 30 uncomplicated T2DM patients that were previously not taking TZD's. This Phase IV, randomized, double-blind, placebo controlled, clinical trial will consist of 3 phases: a screening, a placebo / Pioglitazone phase (12 weeks) and a weight loss period (6-10 weeks). The primary endpoint is to identify the changes in skeletal muscle mitochondria number and gene expression. Secondary endpoints include MRS measured mitochondrial capacity, insulin sensitivity for glucose disposal and insulin suppression of free fatty acids, electron transport chain activity, mitochondrial content and intra hepatic and intra myocellular lipid. Metformin and Sulfonylurea will be used as standardized oral therapy to maintain HbA1C < 7.0. After completing the protocol, patients will be offered a very low calorie liquid diet (800kcal/d) to assist them in losing weight. During this period they will continue on their previously randomized treatment. When patients lose 10% of their body weight, patients will be switched to a weight maintenance diet (meal replacement with 1 can of glucerna at breakfast and lunch with a "healthy" dinner) for 10 days. MRS measured mitochondrial capacity will again be determined to see if weight loss + pioglitazone has more effect on mitochondrial function than pioglitazone alone.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00402012
|United States, Louisiana|
|Pennington Biomedical Research Center|
|Baton Rouge, Louisiana, United States, 70808|
|Principal Investigator:||Steven R Smith, M.D.||Pennington Biomedical Research Center|