Rheumatoid ArthritisPhase 3RAPPARNCT00554853

PPAR-gamma Agonists, Rheumatoid Arthritis and Cardiovascular Disease

A Phase 3 study testing pioglitazone and Sublingual nitroglycerine in people with Rheumatoid Arthritis, run by University of Michigan at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 21 to 100 years
Conditions the study is for: Rheumatoid Arthritis
What is being tested?: pioglitazone and Sublingual nitroglycerine
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 143 participants
Where: 1 siteUnited States
Study dates: Nov 2007to Jan 2013
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 21 to 100 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Michigan
Ann Arbor, Michigan, 48109

Other trials in United States

About this study

Official title: Peroxisome Proliferator-activated Receptor-gamma Agonists, Rheumatoid Arthritis and Cardiovascular Disease

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.

Read the 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.

Conditions: Rheumatoid Arthritis
Being tested: pioglitazone, Sublingual nitroglycerine
Medical subject headings: Arthritis, Rheumatoid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

pioglitazoneDrug
Also called Actos
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
Sublingual nitroglycerineDrug
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.

Study groups in NCT00554853
Study group	Role	What they receive
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. Receives: 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. Receives: Drug: pioglitazone; Drug: Sublingual nitroglycerine

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 8 months

Secondary outcomes (1)

Rheumatoid Arthritis Disease Activity
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.
Measured: 8 mo

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Nov 2007Jan 2013

First posted7 Nov 2007 (estimated)
Study startNov 2007
Primary completionOct 2012
Study completionJan 2013

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
More trials run by University of MichiganThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 143 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00554853
Sponsor's protocol ID: HUM11806
Other IDs: 5R01HL086553
Acronym: RAPPAR
Status last verified: Dec 2016
First submitted: 6 Nov 2007
Last updated: 2 Feb 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

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.
PubMed 21727237
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.
PubMed 23962407
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.
PubMed 24252844

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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An Ascending Dose Study of DKB903 in Participants With Rheumatoid Arthritis (RA) and Participants With Systemic Lupus Erythematosus (SLE)
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Active, not recruitingPhase 2
A Study Evaluating the Safety and Efficacy of Inhaled AP01 in Participants With Progressive Pulmonary Fibrosis
Pulmonary Fibrosis, Progressive Pulmonary Fibrosis

All Rheumatoid Arthritis trials

Study at a glance

From the registry record, last updated by the sponsor on 2 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Peroxisome Proliferator-activated Receptor-gamma Agonists, Rheumatoid Arthritis and Cardiovascular Disease
ClinicalTrials.gov ID: NCT00554853
Acronym / sponsor ID: RAPPAR / HUM11806
Conditions: Rheumatoid Arthritis
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 143 participants (actual)
Lead sponsor: University of MichiganUniversity, hospital or other
Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
Study start: Nov 2007
Primary completion: Oct 2012 (actual)
Study completion: Jan 2013 (actual)
First posted: 7 Nov 2007 (estimated)
Results: Posted 2 Feb 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 2

Arm	Type	Receives
Pioglitazone then placebo	Other	Drug: pioglitazone, Drug: Sublingual nitroglycerineOral 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.
placebo then study drug (pioglitazone)	Other	Drug: pioglitazone, Drug: Sublingual nitroglycerineOral daily placebo for 3 months compared to pioglitazone for 3 months, then crossover after a 2 month washout. Similar doses as mentioned above.

Who may qualify

Ages: 21 to 100 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

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.

Key exclusion criteria (6 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
pioglitazoneAlso: Actosdaily 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	Drug	Pioglitazone then placebo, placebo then study drug (pioglitazone)
Sublingual nitroglycerineUsed 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.	Drug	Pioglitazone then placebo, placebo then study drug (pioglitazone)

Primary outcome

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.

1 secondary outcome

Rheumatoid Arthritis Disease Activity
Time frame: 8 mo

Results and safety

Results posted to the registry on 2 Feb 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Study Drug (Pioglitazone) Then Placebo	72	56
Placebo Then Study Drug (Pioglitazone)	71	64

Primary outcome: Brachial Artery Diameter Change From Baseline in Response to Reactive Hyperemia

Time frame: 8 months. Mean (Inter-Quartile Range). Unit: % changes in diameter of artery

Measure	Study Drug (Pioglitazone) Then Placebo n = 72	Placebo Then Study Drug (Pioglitazone) n = 71
Value	8.3 (4.4 to 17.5)	9.43 (4.3 to 20)

Population analysed: Vascular function parameters were performed in patients with rheumatoid arthritis at baseline and at completion of each arm , as well as at the beginning of crossover following washout period.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: 8 months, but no more than 10 months. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Study Drug (Pioglitazone) Then Placebo, While on Drug	5 of 72 (6.9%)	22 of 72 (30.6%)	Not reported
Study Drug (Pioglitazone) Then Placebo, During Washout	1 of 72 (1.4%)	2 of 72 (2.8%)	Not reported
Study Drug (Pioglitazone) Then Placebo, While on Placebo	0 of 72 (0%)	8 of 72 (11.1%)	Not reported
Placebo Then Study Drug (Pioglitazone) While on Placebo	1 of 71 (1.4%)	12 of 71 (16.9%)	Not reported
Placebo Then Study Drug (Pioglitazone) During Washout	3 of 71 (4.2%)	0 of 71 (0%)	Not reported
Placebo Then Study Drug (Piolglitazone) While on Study Drug	5 of 71 (7%)	9 of 71 (12.7%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 2 Feb 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 21727237Marder 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.
Background: PubMed 23962407Zhao 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.
Derived from this study: PubMed 24252844Marder 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.

Related trials for Rheumatoid Arthritis

RecruitingPhase 2
Study of PTC844 in Participants With Active Rheumatoid Arthritis
Rheumatoid Arthritis
Not yet recruitingPhase 1
An Ascending Dose Study of DKB903 in Participants With Rheumatoid Arthritis (RA) and Participants With Systemic Lupus Erythematosus (SLE)
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Not yet recruitingPhase 1
R-2487 in Patients With Sjogren's Syndrome (SjD)
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RecruitingPhase 1
A Trial in Healthy Adult Participants and Adults With Autoimmune Diseases to Test How HBM7020 is Tolerated and How it Behaves in the Body
Rheumatoid Arthritis, Systemic Lupus Erythematosus
Active, not recruitingPhase 2
A Study Evaluating the Safety and Efficacy of Inhaled AP01 in Participants With Progressive Pulmonary Fibrosis
Pulmonary Fibrosis, Progressive Pulmonary Fibrosis

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Mariana J Kaplan, MD principal investigator

University of Michigan

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing pioglitazone and Sublingual nitroglycerine in people with Rheumatoid Arthritis, run by University of Michigan at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Feb 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Brachial Artery Diameter Change From Baseline in Response to Reactive Hyperemia (time frame: 8 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00554853, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Feb 2017.