Effect of Pioglitazone on Oxidative Load, Inflammatory End-Points and Vascular Reactivity in Obese Non-Diabetic Patients: A Dose Ranging Study

This study has been completed.
Sponsor:
Collaborator:
Takeda Pharmaceuticals North America, Inc.
Information provided by:
Kaleida Health
ClinicalTrials.gov Identifier:
NCT01161394
First received: July 12, 2010
Last updated: NA
Last verified: July 2010
History: No changes posted
  Purpose

Pioglitazone decreases oxidative load, inflammatory end points and improves vascular reactivity in obese patients in a dose dependent manner and that this effect is independent of its glucose lowering effects.


Condition Intervention Phase
Inflammation
Drug: Pioglitazone 15mg
Drug: pioglitazone 30mg
Drug: placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effect of Pioglitazone on Oxidative Load, Inflammatory End-Points and Vascular Reactivity in Obese Non-Diabetic Patients: A Dose Ranging Study

Resource links provided by NLM:


Further study details as provided by Kaleida Health:

Primary Outcome Measures:
  • Inflammation [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Percent change in NFkb at baseline and after 1, 2, 4, 6, and 12 weeks of pioglitazone therapy.


Secondary Outcome Measures:
  • inflammation [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    TBARS (Thiobarbituric acid reactive substances), ortho and meta-tyrosine, 9-HODE and 13-HODE (hydroxyoctadecadieonic acid derivatives), Cellular/nuclear fractions and DNA binding activity of Nuclear Factor kb, Ikb (inhibitory kappa B), TNF-a(Tumor necrosis factor a), ICAM-1 (Intracellular adhesion molecule 1), VCAM-1(Vascular adhesion molecule 1), PAI-1 (Plasminogen Activator Inhibitor -1) and CRP (C-Reactive protein) and %change in vascular reactivity.


Estimated Enrollment: 24
Study Completion Date: October 2003
Arms Assigned Interventions
Experimental: Pioglitazone 15mg
8 patient will receive this drug
Drug: Pioglitazone 15mg
Experimental: pioglitazone 30mg
8 patients will get this drug
Drug: pioglitazone 30mg
Placebo Comparator: Placebo
8 patient will get this drug
Drug: placebo

Detailed Description:

This is a single center, open labeled study. A total of 24 obese patients will be recruited to participate in this study. The study will have three groups of 8 patients each. Subjects will be enrolled into each group by alternate recruitment. Subjects in group one will receive 15mg of pioglitazone; subjects in group two will receive 30 mg of pioglitazone; subjects in group three will receive placebo. All subjects will receive Pioglitazone or placebo for 6 weeks, followed by a 6-week observation period off Pioglitazone/placebo.

At baseline, and at week 1, week 2, week 4, week 6 and month 3 all patients will have blood drawn for TBARS, ortho and meta-tyrosine, 9-HODE and 13-HODE, NF, Ikb, TNF-a, ICAM-1, VCAM-1, PAI-1, AP-1, EGR-1, MMP-2, MMP-9, TIMP, CRP-1, E-Selectin, P-Selectin, Asymmetric dimethylarginine (ADMA), PAPP-A, SAA, MCP-1, IL-6, ROS generation, insulin levels, and CRP.

Post-ischemic dilation of the brachial artery will be used as an index of endothelium-mediated vasodilation. All subjects will have an oral glucose tolerance test (GTT) with 75gm of glucose at Day 0 and at Day 42. Vascular reactivity will be assessed at 0, 6, and at 12 weeks.

  Eligibility

Ages Eligible for Study:   20 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • • Obese (BMI>=30)

    • Age: 20 to 65 years of age inclusive
    • Without established clinical coronary artery disease (documented history or myocardial infarction, typical angina and an exercise ECG positive for ischemia or angiographic evidence of CAD)
    • Good health as evidence by History and Physical exam
    • Female subjects must be:

Postmenopausal for at least one year or Surgically incapable of childbearing (i.e. have had a hysterectomy or tubal ligation) or, if capable of childbearing a subject, must be practicing an acceptable method of contraception.

• Subject will be available for duration of the study and willing to comply with all study requirements.

Exclusion Criteria:

  • • Diabetes Mellitus

    • Allergy or sensitivity to Pioglitazone
    • Current use of Insulin therapy.
    • Coronary event or procedure (myocardial infarction, unstable angina, coronary artery bypass, surgery or coronary angioplasty) in the previous four weeks
    • Hepatic disease (transaminase > 3 times normal)
    • Renal impairment (Creatinine clearance < 50 mL/min)
    • History of drug or alcohol abuse
    • COPD
    • Participation in any other concurrent clinical trial
    • Any other life-threatening, non-cardiac disease
    • Use of an investigational agent or therapeutic regimen within 30 days of study
    • Pregnancy or nursing
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01161394

Locations
United States, New York
Millard Fillmore gates Hospital
Buffalo, New York, United States, 14226
Sponsors and Collaborators
Kaleida Health
Takeda Pharmaceuticals North America, Inc.
Investigators
Principal Investigator: Paresh Dandona, MD Kaleida Health
  More Information

No publications provided

Responsible Party: Paresh Dandona, University at buffalo Kaleida Health
ClinicalTrials.gov Identifier: NCT01161394     History of Changes
Other Study ID Numbers: 1851
Study First Received: July 12, 2010
Last Updated: July 12, 2010
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Inflammation
Pathologic Processes
Pioglitazone
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014