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

Primary Purpose

Inflammation

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Pioglitazone 15mg

pioglitazone 30mg

placebo

About this trial

This is an interventional treatment trial for Inflammation

Eligibility Criteria

20 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Millard Fillmore gates Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Arm Label

Pioglitazone 15mg

pioglitazone 30mg

Placebo

Arm Description

8 patient will receive this drug

8 patients will get this drug

8 patient will get this drug

Outcomes

Primary Outcome Measures

Inflammation

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

Secondary Outcome Measures

inflammation

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.

Full Information

NCT ID

NCT01161394

First Posted

July 12, 2010

Last Updated

January 12, 2022

Sponsor

University at Buffalo

Collaborators

Takeda Pharmaceuticals North America, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT01161394

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2022

Overall Recruitment Status

Completed

Study Start Date

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Primary Completion Date

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Study Completion Date

October 2003 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University at Buffalo

Collaborators

Takeda Pharmaceuticals North America, Inc.

4. Oversight

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Inflammation

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Pioglitazone 15mg

Arm Type

Experimental

Arm Description

8 patient will receive this drug

Arm Title

pioglitazone 30mg

Arm Type

Experimental

Arm Description

8 patients will get this drug

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

8 patient will get this drug

Intervention Type

Drug

Intervention Name(s)

Pioglitazone 15mg

Intervention Type

Drug

Intervention Name(s)

pioglitazone 30mg

Intervention Type

Drug

Intervention Name(s)

placebo

Primary Outcome Measure Information:

Title

Inflammation

Description

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

Time Frame

12 weeks

Secondary Outcome Measure Information:

Title

inflammation

Description

Time Frame

12 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Paresh Dandona, MD

Organizational Affiliation

Kaleida Health

Official's Role

Principal Investigator

Facility Information:

Facility Name

Millard Fillmore gates Hospital

City

Buffalo

State/Province

New York

ZIP/Postal Code

14226

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

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