Rheumatoid Arthritis
Conditions
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.
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.
Interventions
DRUGpioglitazone
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
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.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
University of Michigan
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to 100 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Brachial Artery Diameter Change From Baseline in Response to Reactive Hyperemia | 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
| Measure | Time frame | Description |
|---|---|---|
| Rheumatoid Arthritis Disease Activity | 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. |
Countries
United States
Participant flow
Recruitment details
Participant came into University of Michigan Rheumatology clinic learned about the study and then came in for baseline to sign consent or signed consent at screening visit and then came in for baseline visit at a latter date.
Pre-assignment details
Out of the 144 individuals screened, one was not randomized to either arm.
Participants by arm
| Arm | Count |
|---|---|
| Study Drug (Pioglitazone) Then Placebo Oral daily pioglitazone for 3 months compared to placebo for 3 months,crossover after a 2 month washout. | 72 |
| Placebo Then Study Drug (Pioglitazone) Oral daily placebo for 3 months compared to pioglitazone for 3 months, crossover after a 2 month washout. | 71 |
| Total | 143 |
Baseline characteristics
| Characteristic | Placebo Then Study Drug (Pioglitazone) | Study Drug (Pioglitazone) Then Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 14 Participants | 13 Participants | 27 Participants |
| Age, Categorical Between 18 and 65 years | 57 Participants | 59 Participants | 116 Participants |
| Age, Continuous | 56.0 years STANDARD_DEVIATION 12 | 54.5 years STANDARD_DEVIATION 12.3 | 55.2 years STANDARD_DEVIATION 12.1 |
| Gender Female | 53 Participants | 56 Participants | 109 Participants |
| Gender Male | 18 Participants | 16 Participants | 34 Participants |
| Region of Enrollment United States | 71 participants | 72 participants | 143 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 22 / 72 | 2 / 72 | 8 / 72 | 12 / 71 | 0 / 71 | 9 / 71 |
| serious Total, serious adverse events | 5 / 72 | 1 / 72 | 0 / 72 | 1 / 71 | 3 / 71 | 5 / 71 |
Outcome results
Primary
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.
Time frame: 8 months
Population: 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.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Study Drug (Pioglitazone) Then Placebo | Brachial Artery Diameter Change From Baseline in Response to Reactive Hyperemia | 8.3 % changes in diameter of artery |
| Placebo Then Study Drug (Pioglitazone) | Brachial Artery Diameter Change From Baseline in Response to Reactive Hyperemia | 9.43 % changes in diameter of artery |
Secondary
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.
Time frame: 8 mo
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Drug (Pioglitazone) Then Placebo | Rheumatoid Arthritis Disease Activity | 0.15 mean decrease in DAS28-CRP score | Standard Deviation 1.2 |
| Placebo Then Study Drug (Pioglitazone) | Rheumatoid Arthritis Disease Activity | .31 mean decrease in DAS28-CRP score | Standard Deviation 1.2 |
p-value: 0.63ANCOVA