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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 August 28, 2014