Rheumatoid ArthritisNCT00763139
Inflammation and Insulin Resistance in Rheumatoid Arthritis
A study testing Pioglitazone in people with Rheumatoid Arthritis, run by Vanderbilt University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- Pioglitazone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 34 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2009to Dec 2013
- Phase
- Interventional
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Allergic to pioglitazone
- Active cancer (other than skin cancer)
- HIV infected
- Currently receiving dialysis
- Received an organ or bone marrow transplant
- Heart failure
Show all 14Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt Clinical Research Center
Nashville, Tennessee, 37232-2195
About this study
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.
Read the detailed description
RA is an autoimmune disease that causes long-term inflammation of the joints and sometimes other body tissues, too. Recent studies have found that there is an increased prevalence of coronary artery atherosclerosis, metabolic syndrome, and insulin resistance among people with RA. Furthermore, insulin resistance, which can lead to hyperinsulinemia-too much insulin in the blood-has been associated with RA disease activity and the severity of coronary artery atherosclerosis. These correlations suggest that inflammation and hyperinsulinemia somehow interact and facilitate one another.
Pioglitazone is a prescription drug that reduces insulin resistance and is currently used to treat people with diabetes. This study will determine whether pioglitazone can also be used to effectively treat people with RA. Specifically, the study will evaluate the effect of pioglitazone on inflammation, insulin resistance, and atherosclerosis.
Participation in this study will last about 20 weeks. At an initial 1-hour screening, participants will undergo a physical examination, medical history review, blood sampling, and, if female, a urine pregnancy test. Eligible participants will then return for the first of six monthly study visits. At this first visit, participants will be randomly assigned to receive either pioglitazone or placebo, both of which will be taken daily for 8 weeks. This will be followed by a 4-week wash-out period, during which no study treatments will be taken. Then, at Week 12, participants will begin daily treatments of whatever they were not assigned to originally. This second treatment phase will also last for 8 weeks.
All of the study visits will involve the same tests and procedures. The morning before each study visit, participants will collect their urine in a jug, which they will bring to the clinic. Participants will then undergo blood sampling, blood pressure measurements, and artery stiffness measurements. During the study visits at Weeks 4, 8, 16, and 20, participants will be asked to report on their symptoms, pain, and any adverse effects.
- Conditions
- Rheumatoid Arthritis
- Being tested
- Pioglitazone, Placebo
- Keywords
- RA, Rheumatoid Arthritis
- 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
45 mg by mouth once a day for 8 weeks
PlaceboDrug
By mouth once a day for 8 weeks
| Study group | Role | What they receive |
|---|---|---|
| Placebo First | Experimental | Placebo for first 8 weeks, then washout period for 4 weeks, and finally pioglitazone for 8 weeks. Receives: Drug: Pioglitazone; Drug: Placebo |
| Pioglitazone First | Experimental | Pioglitazone for first 8 weeks, then washout period for 4 weeks, and finally placebo for 8 weeks. Receives: Drug: Pioglitazone; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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: 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: Measured after 8 weeks of treatment
Secondary outcomes (2)
C-reactive Protein (CRP)
Measured: Measured after 8 weeks of treatment
ESR
sed rate
Measured: baseline and after 8 weeks on either placebo or pioglitazone
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2008 (estimated)
- Study startApr 2009
- Primary completionSep 2012
- Study completionDec 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 (2)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Responsible party
- Principal investigator, C. Michael Stein, Vanderbilt University
- Investigators
- Charles M. Stein, MD, Principal investigator, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00763139
- Sponsor's protocol ID
- P60AR056116
- Other IDs
- P60AR056116
- Status last verified
- Nov 2014
- First submitted
- 26 Sep 2008
- Last updated
- 13 Nov 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 24020899Ormseth 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.
PubMed 24782291
Study at a glance
From the registry record, last updated by the sponsor on 13 Nov 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inflammation and Insulin Resistance in Rheumatoid Arthritis
- ClinicalTrials.gov ID
- NCT00763139
- Acronym / sponsor ID
- P60AR056116
- Conditions
- Rheumatoid Arthritis
- Keywords
- RA, Rheumatoid Arthritis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Vanderbilt UniversityUniversity, hospital or other
- Collaborators
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Study start
- Apr 2009
- Primary completion
- Sep 2012 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 30 Sep 2008 (estimated)
- Results
- Posted 13 Nov 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
RA is an autoimmune disease that causes long-term inflammation of the joints and sometimes other body tissues, too. Recent studies have found that there is an increased prevalence of coronary artery atherosclerosis, metabolic syndrome, and insulin resistance among people with RA. Furthermore, insulin resistance, which can lead to hyperinsulinemia-too much insulin in the blood-has been associated with RA disease activity and the severity of coronary artery atherosclerosis. These correlations suggest that inflammation and hyperinsulinemia somehow interact and facilitate one another.
Pioglitazone is a prescription drug that reduces insulin resistance and is currently used to treat people with diabetes. This study will determine whether pioglitazone can also be used to effectively treat people with RA. Specifically, the study will evaluate the effect of pioglitazone on inflammation, insulin resistance, and atherosclerosis.
Participation in this study will last about 20 weeks. At an initial 1-hour screening, participants will undergo a physical examination, medical history review, blood sampling, and, if female, a urine pregnancy test. Eligible participants will then return for the first of six monthly study visits. At this first visit, participants will be randomly assigned to receive either pioglitazone or placebo, both of which will be taken daily for 8 weeks. This will be followed by a 4-week wash-out period, during which no study treatments will be taken. Then, at Week 12, participants will begin daily treatments of whatever they were not assigned to originally. This second treatment phase will also last for 8 weeks.
All of the study visits will involve the same tests and procedures. The morning before each study visit, participants will collect their urine in a jug, which they will bring to the clinic. Participants will then undergo blood sampling, blood pressure measurements, and artery stiffness measurements. During the study visits at Weeks 4, 8, 16, and 20, participants will be asked to report on their symptoms, pain, and any adverse effects.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo First | Experimental | Drug: Pioglitazone, Drug: PlaceboPlacebo for first 8 weeks, then washout period for 4 weeks, and finally pioglitazone for 8 weeks. |
| Pioglitazone First | Experimental | Drug: Pioglitazone, Drug: PlaceboPioglitazone for first 8 weeks, then washout period for 4 weeks, and finally placebo for 8 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (14 listed)
- Allergic to pioglitazone
- Active cancer (other than skin cancer)
- HIV infected
- Currently receiving dialysis
- Received an organ or bone marrow transplant
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: Actos45 mg by mouth once a day for 8 weeks | Drug | Pioglitazone First, Placebo First |
| PlaceboBy mouth once a day for 8 weeks | Drug | Pioglitazone First, Placebo First |
Primary outcome
Disease Activity Score Based on 28-joint Disease Activity Score (DAS28)
Time frame: Measured after 8 weeks of treatment
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
Homeostasis Model Assessment (HOMA) for Insulin Sensitivity
Time frame: Measured after 8 weeks of treatment
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
2 secondary outcomes
C-reactive Protein (CRP)
Time frame: Measured after 8 weeks of treatment
ESR
Time frame: baseline and after 8 weeks on either placebo or pioglitazone
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Nov 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 24020899Ormseth 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.
- Derived from this study: PubMed 24782291Ormseth 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.
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)
Rheumatoid Arthritis and Systemic Lupus Erythematosus
Not yet recruitingPhase 1
R-2487 in Patients With Sjogren's Syndrome (SjD)
Sjogren's Syndrome, Sjögren
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.
Charles M. Stein, MD principal investigator
Vanderbilt University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Pioglitazone in people with Rheumatoid Arthritis, run by Vanderbilt University 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 4 inclusion and 14 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 13 Nov 2014. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Nov 2014). 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?
Disease Activity Score Based on 28-joint Disease Activity Score (DAS28) (time frame: Measured after 8 weeks of treatment). The study lists 2 primary outcomes in all. 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 NCT00763139, which also lists 2 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 13 Nov 2014.