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

NCT ID: NCT01161394

Last Updated: 2022-01-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Completion Date: 2003-10-31

Brief Summary

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.

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.

Conditions

Inflammation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pioglitazone 15mg

8 patient will receive this drug

Group Type: EXPERIMENTAL

Pioglitazone 15mg

Intervention Type: DRUG

pioglitazone 30mg

8 patients will get this drug

Group Type: EXPERIMENTAL

pioglitazone 30mg

Intervention Type: DRUG

Placebo

8 patient will get this drug

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

Interventions

Pioglitazone 15mg

Intervention Type: DRUG

pioglitazone 30mg

Intervention Type: DRUG

placebo

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Takeda Pharmaceuticals North America, Inc.

INDUSTRY

Sponsor Role: collaborator

University at Buffalo

OTHER

Sponsor Role: lead

Responsible Party

Paresh Dandona

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Paresh Dandona, MD

Role: PRINCIPAL_INVESTIGATOR

Kaleida Health

Locations

Millard Fillmore gates Hospital

Buffalo, New York, United States

Countries

United States

Other Identifiers

1851

Identifier Type: -

Identifier Source: org_study_id