Inflammation and Insulin Resistance in Rheumatoid Arthritis

NCT00763139 | Completed Results DMC

• 1 other identifier: P60AR056116
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Rheumatoid Arthritis

Keywords

RA; Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (2)

• Disease Activity Score Based on 28-joint Disease Activity Score (DAS28)

  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

  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 Outcomes (2)

• C-reactive Protein (CRP)

  Measured after 8 weeks of treatment

• ESR

  baseline and after 8 weeks on either placebo or pioglitazone

Study Arms (2)

Placebo First

EXPERIMENTAL

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

Drug: Pioglitazone; Drug: Placebo

Pioglitazone First

EXPERIMENTAL

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

Drug: Pioglitazone; Drug: Placebo

Interventions

Pioglitazone DRUG

45 mg by mouth once a day for 8 weeks

Also known as: Actos

Pioglitazone First; Placebo First

Placebo DRUG

By mouth once a day for 8 weeks

Pioglitazone First; Placebo First

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Vanderbilt University: lead
• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): collaborator

Study Sites (1)

Vanderbilt Clinical Research Center

Nashville, Tennessee, 37232-2195, United States

Location

Related Publications (2)

• 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.

  PMID: 24020899 RESULT

• 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.

  PMID: 24782291 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Pioglitazone

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

Study relatively small, but efficiently designed. Crossover design has the advantage of comparing changes in the same patient and the disadvantage that subtle, undetected carryover effects may occur. 8 week drug exposure shorter than most trials.

Results Point of Contact

• Title: Dr. Charles Michael Stein
• Organization: Vanderbilt

mike.stein@vanderbilt.edu

615-936-3420

Study Officials

• Charles M. Stein, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dan May Professor of Medicine, Professor of Pharmacology, Associate Director of the Division of Clinical Pharmacology

Study Record Dates

• First Submitted: September 26, 2008
• First Posted: September 30, 2008
• Study Start: April 1, 2009
• Primary Completion: September 1, 2012
• Study Completion: December 1, 2013
• Last Updated: November 13, 2014
• Results First Posted: November 13, 2014

Record last verified: 2014-11

Locations

US (1)