PPAR-gamma Agonists, Rheumatoid Arthritis and Cardiovascular Disease

NCT00554853 | Completed Phase 3 Results

• 2 other identifiers: HUM118065R01HL086553
• Study Type: interventional
• Target: 143
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• Brachial Artery Diameter Change From Baseline in Response to Reactive Hyperemia

  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.

  8 months

Secondary Outcomes (1)

• Rheumatoid Arthritis Disease Activity

  8 mo

Study Arms (2)

Pioglitazone then placebo

OTHER

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; Drug: Sublingual nitroglycerine

placebo then study drug (pioglitazone)

OTHER

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; Drug: Sublingual nitroglycerine

Interventions

pioglitazone DRUG

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

Also known as: Actos

Pioglitazone then placebo; placebo then study drug (pioglitazone)

Sublingual nitroglycerine DRUG

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.

Pioglitazone then placebo; placebo then study drug (pioglitazone)

Eligibility Criteria

• Age: 21 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Michigan: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Related Publications (3)

• Marder W, Khalatbari S, Myles JD, Hench R, Yalavarthi S, Lustig S, Brook R, Kaplan MJ. Interleukin 17 as a novel predictor of vascular function in rheumatoid arthritis. Ann Rheum Dis. 2011 Sep;70(9):1550-5. doi: 10.1136/ard.2010.148031. Epub 2011 Jul 4.

  PMID: 21727237 BACKGROUND

• Zhao W, Berthier CC, Lewis EE, McCune WJ, Kretzler M, Kaplan MJ. The peroxisome-proliferator activated receptor-gamma agonist pioglitazone modulates aberrant T cell responses in systemic lupus erythematosus. Clin Immunol. 2013 Oct;149(1):119-32. doi: 10.1016/j.clim.2013.07.002. Epub 2013 Jul 20.

  PMID: 23962407 BACKGROUND

• Marder W, Khalatbari S, Myles JD, Hench R, Lustig S, Yalavarthi S, Parameswaran A, Brook RD, Kaplan MJ. The peroxisome proliferator activated receptor-gamma pioglitazone improves vascular function and decreases disease activity in patients with rheumatoid arthritis. J Am Heart Assoc. 2013 Nov 19;2(6):e000441. doi: 10.1161/JAHA.113.000441.

  PMID: 24252844 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

Results Point of Contact

• Title: PPAR-gamma agonist, rheumatoid arthritis and cardiovascular disease
• Organization: UMichigan

makaplan@umich.edu

734-936-7905

Study Officials

• Mariana J Kaplan, MD

  University of Michigan

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: November 6, 2007
• First Posted: November 7, 2007
• Study Start: November 1, 2007
• Primary Completion: October 1, 2012
• Study Completion: January 1, 2013
• Last Updated: February 2, 2017
• Results First Posted: February 2, 2017

Record last verified: 2016-12

Locations

US (1)