Try our beta test site

PPAR-gamma Agonists, Rheumatoid Arthritis and Cardiovascular Disease (RAPPAR)

This study has been completed.
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Mariana Kaplan, University of Michigan
ClinicalTrials.gov Identifier:
NCT00554853
First received: November 6, 2007
Last updated: December 7, 2016
Last verified: December 2016
  Purpose
Patients with rheumatoid arthritis have a significantly higher risk to develop heart attacks and other complications of their blood vessels. New therapies are needed to prevent this complication. The purpose of this study is to establish the role of the medication pioglitazone in improving the function of the blood vessels and heart and decreasing the risk of future atherosclerosis development in individuals with rheumatoid arthritis. As a secondary aim-point, we will evaluate the efficacy of pioglitazone in improving rheumatoid arthritis disease activity and markers of inflammation.

Condition Intervention Phase
Rheumatoid Arthritis
Drug: pioglitazone
Drug: Sublingual nitroglycerine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Peroxisome Proliferator-activated Receptor-gamma Agonists, Rheumatoid Arthritis and Cardiovascular Disease

Resource links provided by NLM:


Further study details as provided by University of Michigan:

Primary Outcome Measures:
  • Brachial Artery Diameter Change From Baseline in Response to Reactive Hyperemia [ Time Frame: 8 months ]
    This measure represents the percentage change in diameter of brachial artery in response to reactive hyperemia. The data is presented intentionally and only for the results at the conclusion of the study.


Secondary Outcome Measures:
  • Rheumatoid Arthritis Disease Activity [ Time Frame: 8 mo ]

    Quantification of disease activity using validated assessments (disease activity score on 28 joints (DAS28) and and C-reactive protein ( CRP) (Inflammatory marker) as a combined score (DAS-28CRP)).

    Mean decrease in DAS-28-CRP score when compared to baseline was measured. The range of DAS-28-CRP is 0-10, with 0 meaning no active disease detected and 10 being the most severe active disease detected by joint count and C-reactive protein levels in blood.



Enrollment: 143
Study Start Date: November 2007
Study Completion Date: January 2013
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Pioglitazone then placebo
Oral daily pioglitazone 30 mg tablets daily for 2 weeks, followed by 45 mg daily tablets until end of study for 3 months compared to placebo in tablets of equal presentation for 3 months, then crossover after a 2 month washout.
Drug: pioglitazone
daily dose, 30 mg daily for 2 weeks followed by 45 mg daily until completing 3 months unless higher dose not tolerated in which case patient remained at 30 mg daily
Other Name: Actos
Drug: Sublingual nitroglycerine
Used during nitroglycerin-mediated dilatation vascular function measures in both arms of the study if patient's blood pressure permitted. One single tablet was used per vascular test performed.
placebo then study drug (pioglitazone)
Oral daily placebo for 3 months compared to pioglitazone for 3 months, then crossover after a 2 month washout. Similar doses as mentioned above.
Drug: pioglitazone
daily dose, 30 mg daily for 2 weeks followed by 45 mg daily until completing 3 months unless higher dose not tolerated in which case patient remained at 30 mg daily
Other Name: Actos
Drug: Sublingual nitroglycerine
Used during nitroglycerin-mediated dilatation vascular function measures in both arms of the study if patient's blood pressure permitted. One single tablet was used per vascular test performed.

Detailed Description:

This study will establish the role of pioglitazone in improvement of endothelial function, arterial compliance and disease activity in patients with rheumatoid arthritis. This will be a placebo-controlled, double blind, cross-over trial.

Two of the measures which were initially listed as separate outcome measures: (Decrease in inflammation) and Efficacy of pioglitazone in improving rheumatoid arthritis disease activity and markers of inflammation are now shown as a combined score (DAS-28-CRP). The Risks or Side Effects as an outcome measure would be duplicative of the tables in the adverse event section and therefore were deleted as an outcome measure.

  Eligibility

Ages Eligible for Study:   21 Years to 100 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Women on adequate contraception if they are of child-bearing age.
  • Meet revised ACR criteria for RA.
  • Stable doses of DMARDS,biologic agents and or corticosteroids for at least 3 months.

Exclusion Criteria:

  • Pregnant or lactating women.
  • Current smokers or individuals who smoked in the last 6 months.
  • Diagnosis of Diabetes, heart failure, or infection.
  • Current diagnosis of malignant disease except for basal cell or squamous cell carcinoma of the skin.
  • No active liver disease.
  • No cholesterol-lowering medications or oral hypoglycemic agents.
  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: NCT00554853

Locations
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
Sponsors and Collaborators
University of Michigan
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
Principal Investigator: Mariana J Kaplan, MD University of Michigan
  More Information

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Mariana Kaplan, Associate Professor, University of Michigan
ClinicalTrials.gov Identifier: NCT00554853     History of Changes
Other Study ID Numbers: HUM11806
5R01HL086553 ( US NIH Grant/Contract Award Number )
Study First Received: November 6, 2007
Results First Received: December 18, 2013
Last Updated: December 7, 2016

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Cardiovascular Diseases
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Pioglitazone
Nitroglycerin
Hypoglycemic Agents
Physiological Effects of Drugs
Vasodilator Agents

ClinicalTrials.gov processed this record on March 23, 2017