Inflammation and Insulin Resistance in Rheumatoid Arthritis

November 12, 2014 updated by: C. Michael Stein, Vanderbilt University
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

34

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Tennessee
      • Nashville, Tennessee, United States, 37232-2195
        • Vanderbilt Clinical Research Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Placebo First
Placebo for first 8 weeks, then washout period for 4 weeks, and finally pioglitazone for 8 weeks.
Drug: Pioglitazone
45 mg by mouth once a day for 8 weeks
Other Names:
  • Actos
Drug: Placebo
By mouth once a day for 8 weeks
Experimental: Pioglitazone First
Pioglitazone for first 8 weeks, then washout period for 4 weeks, and finally placebo for 8 weeks.
Drug: Pioglitazone
45 mg by mouth once a day for 8 weeks
Other Names:
  • Actos
Drug: Placebo
By mouth once a day for 8 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease Activity Score Based on 28-joint Disease Activity Score (DAS28)
Time Frame: Measured after 8 weeks of treatment
A measure of disease activity based upon tender joint count of 28 joints, swollen joint count of 28 joints, erythrocyte sedimentation rate, and global disease activity (GH) as reported by participant. Calculation is as follows: DAS28=0.56*sqrt(t28) + 0.28*sqrt(sw28) + 0.70*Ln(ESR) + 0.014*GH
Measured after 8 weeks of treatment
Homeostasis Model Assessment (HOMA) for Insulin Sensitivity
Time Frame: Measured after 8 weeks of treatment
Homa is a measure of insulin sensitivity, using glucose measured in mmol/L and insulin measured in milliUnits per liter (mU/L) Calculated using the formula Glucose * Insulin/22/5
Measured after 8 weeks of treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
C-reactive Protein (CRP)
Time Frame: Measured after 8 weeks of treatment
Measured after 8 weeks of treatment
ESR
Time Frame: baseline and after 8 weeks on either placebo or pioglitazone
sed rate
baseline and after 8 weeks on either placebo or pioglitazone

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Vanderbilt University

Collaborators

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

Investigators

  • Principal Investigator: Charles M. Stein, MD, Vanderbilt University Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2009

Primary Completion (Actual)

September 1, 2012

Study Completion (Actual)

December 1, 2013

Study Registration Dates

First Submitted

September 26, 2008

First Submitted That Met QC Criteria

September 29, 2008

First Posted (Estimate)

September 30, 2008

Study Record Updates

Last Update Posted (Estimate)

November 13, 2014

Last Update Submitted That Met QC Criteria

November 12, 2014

Last Verified

November 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P60AR056116 (U.S. NIH Grant/Contract)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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