"TAKE TIME" Pioglitazone Reverses Defects in Mitochondrial Biogenesis in Patients With T2DM
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 4

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Pioglitazone
Intervention type(s): Drug
Intervention description(s): 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 intervention name(s): TZD
Intervention MeSH terms: Pioglitazone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Diabetes Mellitus, Type 2