Inflammation and Insulin Resistance in Rheumatoid Arthritis

NCT ID: NCT00763139

Last Updated: 2014-11-13

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

34 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-04-30

Study Completion Date

2013-12-31

Brief Summary

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Rheumatoid arthritis (RA) is a form of arthritis that causes pain, swelling, stiffness, and loss of function in the joints. Over time, joint deformity, joint destruction, and loss of function can occur. Current treatment aims to improve symptoms, but there is no cure for the disease. Pioglitazone is drug that is effective in treating people with diabetes. This study will determine whether pioglitazone can also be used to effectively treat people with RA.

Detailed Description

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RA is an autoimmune disease that causes long-term inflammation of the joints and sometimes other body tissues, too. Recent studies have found that there is an increased prevalence of coronary artery atherosclerosis, metabolic syndrome, and insulin resistance among people with RA. Furthermore, insulin resistance, which can lead to hyperinsulinemia-too much insulin in the blood-has been associated with RA disease activity and the severity of coronary artery atherosclerosis. These correlations suggest that inflammation and hyperinsulinemia somehow interact and facilitate one another.

Pioglitazone is a prescription drug that reduces insulin resistance and is currently used to treat people with diabetes. This study will determine whether pioglitazone can also be used to effectively treat people with RA. Specifically, the study will evaluate the effect of pioglitazone on inflammation, insulin resistance, and atherosclerosis.

Participation in this study will last about 20 weeks. At an initial 1-hour screening, participants will undergo a physical examination, medical history review, blood sampling, and, if female, a urine pregnancy test. Eligible participants will then return for the first of six monthly study visits. At this first visit, participants will be randomly assigned to receive either pioglitazone or placebo, both of which will be taken daily for 8 weeks. This will be followed by a 4-week wash-out period, during which no study treatments will be taken. Then, at Week 12, participants will begin daily treatments of whatever they were not assigned to originally. This second treatment phase will also last for 8 weeks.

All of the study visits will involve the same tests and procedures. The morning before each study visit, participants will collect their urine in a jug, which they will bring to the clinic. Participants will then undergo blood sampling, blood pressure measurements, and artery stiffness measurements. During the study visits at Weeks 4, 8, 16, and 20, participants will be asked to report on their symptoms, pain, and any adverse effects.

Conditions

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Rheumatoid Arthritis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Placebo First

Placebo for first 8 weeks, then washout period for 4 weeks, and finally pioglitazone for 8 weeks.

Group Type EXPERIMENTAL

Pioglitazone

Intervention Type DRUG

45 mg by mouth once a day for 8 weeks

Placebo

Intervention Type DRUG

By mouth once a day for 8 weeks

Pioglitazone First

Pioglitazone for first 8 weeks, then washout period for 4 weeks, and finally placebo for 8 weeks.

Group Type EXPERIMENTAL

Pioglitazone

Intervention Type DRUG

45 mg by mouth once a day for 8 weeks

Placebo

Intervention Type DRUG

By mouth once a day for 8 weeks

Interventions

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Pioglitazone

45 mg by mouth once a day for 8 weeks

Intervention Type DRUG

Placebo

By mouth once a day for 8 weeks

Intervention Type DRUG

Other Intervention Names

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Actos

Eligibility Criteria

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Inclusion Criteria

* Meets the American College of Rheumatology (ACR) criteria for the diagnosis of rheumatoid arthritis (RA)
* Stable disease activity, as evidenced by no change in immunomodulating or anti-inflammatory therapy in the 1 month before study entry
* Moderate disease activity, as reflected by a minimum of three swollen and tender joints
* If female of childbearing potential, willing to use effective method of contraception

Exclusion Criteria

* Allergic to pioglitazone
* Active cancer (other than skin cancer)
* HIV infected
* Currently receiving dialysis
* Received an organ or bone marrow transplant
* Heart failure
* Severe edema, as judged by the principal investigator
* Diabetes mellitus requiring drug therapy: levels of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than twice the upper limit of normal
* Underwent major surgery in the 3 months before study entry
* Severe comorbid condition that is likely to compromise survival or study participation
* Currently receiving gemfibrozil or rifampin
* Osteoporosis and not receiving osteoporosis medications
* Unwillingness, or other inability, to cooperate with study procedures
* Pregnancy
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

NIH

Sponsor Role collaborator

Vanderbilt University

OTHER

Sponsor Role lead

Responsible Party

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C. Michael Stein

Dan May Professor of Medicine, Professor of Pharmacology, Associate Director of the Division of Clinical Pharmacology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Charles M. Stein, MD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University Medical Center

Locations

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Vanderbilt Clinical Research Center

Nashville, Tennessee, United States

Site Status

Countries

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United States

References

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Ormseth MJ, Oeser AM, Cunningham A, Bian A, Shintani A, Solus J, Tanner S, Stein CM. Peroxisome proliferator-activated receptor gamma agonist effect on rheumatoid arthritis: a randomized controlled trial. Arthritis Res Ther. 2013;15(5):R110. doi: 10.1186/ar4290.

Reference Type RESULT
PMID: 24020899 (View on PubMed)

Ormseth MJ, Oeser AM, Cunningham A, Bian A, Shintani A, Solus J, Tanner SB, Stein CM. Reversing vascular dysfunction in rheumatoid arthritis: improved augmentation index but not endothelial function with peroxisome proliferator-activated receptor gamma agonist therapy. Arthritis Rheumatol. 2014 Sep;66(9):2331-8. doi: 10.1002/art.38686.

Reference Type DERIVED
PMID: 24782291 (View on PubMed)

Other Identifiers

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P60AR056116

Identifier Type: NIH

Identifier Source: secondary_id

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P60AR056116

Identifier Type: NIH

Identifier Source: org_study_id

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