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Inflammation and Insulin Resistance in Rheumatoid Arthritis

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
C. Michael Stein, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT00763139
First received: September 26, 2008
Last updated: November 12, 2014
Last verified: November 2014
  Purpose

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.


Condition Intervention
Rheumatoid Arthritis
Drug: Pioglitazone
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Basic Science
Official Title: Inflammation and Insulin Resistance in Rheumatoid Arthritis

Resource links provided by NLM:


Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • Disease Activity Score Based on 28-joint Disease Activity Score (DAS28) [ Time Frame: Measured after 8 weeks of treatment ] [ Designated as safety issue: No ]
    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

  • Homeostasis Model Assessment (HOMA) for Insulin Sensitivity [ Time Frame: Measured after 8 weeks of treatment ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • C-reactive Protein (CRP) [ Time Frame: Measured after 8 weeks of treatment ] [ Designated as safety issue: No ]
  • ESR [ Time Frame: baseline and after 8 weeks on either placebo or pioglitazone ] [ Designated as safety issue: No ]
    sed rate


Enrollment: 34
Study Start Date: April 2009
Study Completion Date: December 2013
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Actos
Drug: Placebo
By mouth once a day for 8 weeks
Other Name: placebo
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 Name: Actos
Drug: Placebo
By mouth once a day for 8 weeks
Other Name: placebo

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00763139

Locations
United States, Tennessee
Vanderbilt Clinical Research Center
Nashville, Tennessee, United States, 37232-2195
Sponsors and Collaborators
Vanderbilt University
Investigators
Principal Investigator: Charles M. Stein, MD Vanderbilt University
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: C. Michael Stein, Dan May Professor of Medicine, Professor of Pharmacology, Associate Director of the Division of Clinical Pharmacology, Vanderbilt University
ClinicalTrials.gov Identifier: NCT00763139     History of Changes
Other Study ID Numbers: P60 AR056116, P60AR056116
Study First Received: September 26, 2008
Results First Received: May 21, 2014
Last Updated: November 12, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Vanderbilt University:
RA
Rheumatoid Arthritis

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Inflammation
Insulin Resistance
Autoimmune Diseases
Connective Tissue Diseases
Glucose Metabolism Disorders
Hyperinsulinism
Immune System Diseases
Joint Diseases
Metabolic Diseases
Musculoskeletal Diseases
Pathologic Processes
Rheumatic Diseases
Pioglitazone
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 20, 2014