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

Sponsor

University at Buffalo (Other)

Overall Status

Completed

CT.gov ID

NCT01161394

Collaborator

Takeda Pharmaceuticals North America, Inc. (Industry)

Enrollment

Location

Arms

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Inflammation	Drug: Pioglitazone 15mg Drug: pioglitazone 30mg Drug: placebo	Phase 4

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

24 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (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

Actual Study Completion Date :

Oct 1, 2003

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Outcome Measures

Primary Outcome Measures

Inflammation [12 weeks]
Percent change in NFkb at baseline and after 1, 2, 4, 6, and 12 weeks of pioglitazone therapy.

Secondary Outcome Measures

inflammation [12 weeks]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

Locations

	Site	City	State	Country	Postal Code
1	Millard Fillmore gates Hospital	Buffalo	New York	United States	14226

Sponsors and Collaborators

University at Buffalo
Takeda Pharmaceuticals North America, Inc.

Investigators

Principal Investigator: Paresh Dandona, MD, Kaleida Health

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Paresh Dandona, Principal Investigator, University at Buffalo

ClinicalTrials.gov Identifier:

NCT01161394

Other Study ID Numbers:

1851

First Posted:

Jul 13, 2010

Last Update Posted:

Jan 27, 2022

Last Verified:

Jan 1, 2022

Additional relevant MeSH terms:

Inflammation

Pioglitazone

Study Results

No Results Posted as of Jan 27, 2022