"TAKE TIME" Pioglitazone Reverses Defects in Mitochondrial Biogenesis in Patients With T2DM

NCT00402012 | Completed Phase 4 DMC

• 1 other identifier: PBRC 26027
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Diabetes Mellitus, Type 2

Keywords

Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (1)

• Change in skeletal muscle mitochondrial number (electron microscopy + qPCR of mtDNA) and mitochondrial gene expression in T2DM patients treated with pioglitazone (vs. placebo)

  baseline and after intervention

Secondary Outcomes (3)

• insulin sensitivity for insulin suppression of free fatty acid and glucose disposal

  baseline and after intervention

• electron transport chain activity; mitochondrial content by MRS (ATP max)

  baseline and after intervention

• intra hepatic and intra myocellular lipid by MRS; mitochondrial content by MRS (ATP max) post weight loss period

  baseline ,after treatment and after weight loss

Study Arms (2)

1

NO INTERVENTION

2

EXPERIMENTAL

Drug: Pioglitazone

Interventions

Pioglitazone DRUG

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.

Also known as: TZD

2

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women aged 18-70 with Type 2 diabetes as defined by:
• Fasting plasma glucose \> 126 mg/dL at entry
• Or a two-hour OGTT glucose \> 200mg/dL
• Or current treatment with one or two oral anti-diabetic drugs, except TZD
• Or currently using insulin
• Fasting plasma glucose \< 200mg/dL at entry
• BMI \>27.0 and \<45.0kg/m2
• Adequate contraception for women (including, but not limited to: oral contraception, hysterectomy, tubal ligation, or post-menopausal as defined by \> 6 months without a menstrual cycle and FSH \> 40 mIU/ml).

You may not qualify if:

• Significant renal, cardiac, liver, lung, or neurological disease (controlled hypertension is acceptable if baseline bp \< 140/90 on medications).
• Prior use of other thiazolidinediones (rosiglitazone \[AVANDIATM\], pioglitazone \[ACTOSTM\])
• Use of drugs known to affect energy metabolism or body weight: including, but not limited to: orlistat, sibutramine, ephedrine, phenylpropanolamine, corticosterone, etc.
• Pregnancy
• Alcohol or other drug abuse
• Unwilling or unable to abstain from caffeine (48h) and tobacco (24h) prior to metabolic rate measurements
• Increased liver function tests at baseline (AST/ALT/GGT/or alkaline phosphatase greater than 2.5 times the upper limit of normal)
• Metal objects that would interfere with the measurement of body composition /MRS such as implanted rods, surgical clips, etc.
• HbA1C of \> 10%.
• history of deep vein thrombosis (DVT) or pulmonary embolism (PE)
• varicose veins
• major surgery on the abdomen, pelvis, or lower extremities within previous 3 months
• cancer (active malignancy with or without concurrent chemotherapy)
• rheumatoid disease
• bypass graft in limb

Sponsors & Collaborators

• Pennington Biomedical Research Center: lead
• Takeda Pharmaceuticals North America, Inc.: collaborator

Study Sites (1)

Pennington Biomedical Research Center

Baton Rouge, Louisiana, 70808, United States

Location

Related Publications (3)

• Bajpeyi S, Myrland CK, Covington JD, Obanda D, Cefalu WT, Smith SR, Rustan AC, Ravussin E. Lipid in skeletal muscle myotubes is associated to the donors' insulin sensitivity and physical activity phenotypes. Obesity (Silver Spring). 2014 Feb;22(2):426-34. doi: 10.1002/oby.20556. Epub 2013 Sep 10.

  PMID: 23818429 DERIVED

• Bajpeyi S, Pasarica M, Moro C, Conley K, Jubrias S, Sereda O, Burk DH, Zhang Z, Gupta A, Kjems L, Smith SR. Skeletal muscle mitochondrial capacity and insulin resistance in type 2 diabetes. J Clin Endocrinol Metab. 2011 Apr;96(4):1160-8. doi: 10.1210/jc.2010-1621. Epub 2011 Feb 9.

  PMID: 21307136 DERIVED

• Costford SR, Bajpeyi S, Pasarica M, Albarado DC, Thomas SC, Xie H, Church TS, Jubrias SA, Conley KE, Smith SR. Skeletal muscle NAMPT is induced by exercise in humans. Am J Physiol Endocrinol Metab. 2010 Jan;298(1):E117-26. doi: 10.1152/ajpendo.00318.2009. Epub 2009 Nov 3.

  PMID: 19887595 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Pioglitazone

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Steven R Smith, M.D.

  Pennington Biomedical Research Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Medical Doctor

Study Record Dates

• First Submitted: November 17, 2006
• First Posted: November 22, 2006
• Study Start: November 1, 2006
• Primary Completion: December 1, 2007
• Study Completion: December 1, 2007
• Last Updated: December 18, 2015

Record last verified: 2015-12

Locations

US (1)