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Diabetes Mellitus, Type 2Phase 4NCT00402012

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

A Phase 4 study testing Pioglitazone in people with Diabetes Mellitus, Type 2, run by Pennington Biomedical Research Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Diabetes Mellitus, Type 2
What is being tested?
Pioglitazone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
1 siteUnited States
Study dates
Nov 2006to Dec 2007
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).

Who cannot join

  • 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
Show all 20Show fewer
  • 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%.
  • NYHA class III/IV CHF is an exclusionary cardiac condition.
  • 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
  • known genetic factor (Factor V Leiden, etc) or hypercoagulable state
  • diagnosed peripheral arterial or vascular disease, or intermittent claudication
  • family history of primary DVT or PE (pulmonary embolism)
  • peripheral neuropathy

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Pennington Biomedical Research Center

    Baton Rouge, Louisiana, 70808

Other trials in United States

About this study

Official title: 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.

Read the 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.

Being tested
Pioglitazone
Keywords
Diabetes Mellitus, Type 2
Medical subject headings
Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PioglitazoneDrug

    Also called TZD

    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.

Study groups in NCT00402012
Study groupRoleWhat they receive
1No interventionNot described
2ExperimentalNot described
Receives: Drug: Pioglitazone

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: baseline and after intervention

Secondary outcomes (3)

  1. insulin sensitivity for insulin suppression of free fatty acid and glucose disposal

    Measured: baseline and after intervention

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

    Measured: baseline and after intervention

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

    Measured: baseline ,after treatment and after weight loss

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Nov 2006 (estimated)
  2. Study startNov 2006
  3. Primary completionDec 2007
  4. Study completionDec 2007

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00402012
Sponsor's protocol ID
PBRC 26027
Status last verified
Dec 2015
First submitted
17 Nov 2006
Last updated
18 Dec 2015
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 23818429

  • 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.

    PubMed 21307136

  • 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.

    PubMed 19887595

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Pioglitazone in people with Diabetes Mellitus, Type 2, run by Pennington Biomedical Research Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00402012, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2015.

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