Exploratory Trial to Evaluate Premature Endothelial Dysfunction in Early Rheumatoid Arthritis(RA)Compared to Patients With Established RA, and Normal Subjects

NCT01499732 | Completed

• 1 other identifier: IM101-320
• Study Type: observational
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Premature Endothelial Dysfunction is present in patients with early rheumatoid arthritis.

Conditions

Premature Endothelial Dysfunction; Rheumatoid Arthritis; Healthy

Keywords

Premature endothelial dysfunction; Early Rheumatoid Arthritis; established rheumatoid arthritis; Premature endothelial dysfunction in early rheumatoid arthritis; Premature endothelial dysfunction in established rheumatoid arthritis; Endothelial function in healthy subjects

Outcome Measures

Primary Outcomes (1)

• To evalute the presence of endothelial dysfunction in patients with rheumatoid arthritis utilizing PET/CT scan with cold pressor test.

  Endothelial dysfunction will be defined as myocardial blood flow (MBF)during cold pressor test (CPT)of less than or equal to 40%

  5 months

Secondary Outcomes (1)

• To evaluate the relationship between PET Scan findings and biomarkers (inflammatory, cardiovascular risk and endothelial dysfunction), and outcome measures

  5 months

Study Arms (3)

Early Rheumatoid Arthritis

Subjects currently experiencing active early rheumatoid arthritis (duration of symptoms \< or = 2 years) according to the 2010 ACR/EULAR criteria for the diagnosis of RA at screening. Must be drug naive (no prior treatment with traditional disease-modifying antirrheumatic drugs (DMARDs), or biologic response modifying agents)

Healthy subjects without rheumatoid arthritis

Healthy subjects without rheumatoid arthritis

Established Rheumatoid Arthritis

Subjects currently experiencing active established rheumatoid arthritis (duration fo symptoms \> or = 2 years) according to the 2010 ACR/EULAR criteria at screening. Subjects with active established RA currently receiving methotrexate, must have received it for at least 12 weeks, and at a stable dose (\> or = 15 mg/week) for at least 6 weeks prior to screening. They must be biologic naive, and must recieve at least 5mg oral folic acid weekly

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Five adults (\>18 years of age), male or non pregnant, non nursing female with active early rheumatoid arthritis (\<2 years), five adults, male or non-pregnant, non nursing female with active established rheumatoid arthritis (\>2 years), and five healthy adults, male or non-pregnant, non nursing female without RA are to be enrolled.

You may qualify if:

• Group 1
• Subjects currently experiencing active early RA (duration of symptoms ≤ 2 years) according to the 2010 ACR/EULAR criteria for the diagnosis of RA at screening.
• Subjects with early RA must be drug naïve (no prior treatment with traditional disease-modifying antirheumatic drugs (DMARDs), or biologic response modifying agents).
• Group 2
• Subjects currently experiencing active established RA (duration of symptoms ≥ 2 years) according to the 2010 ACR/EULAR criteria for the diagnosis of RA at screening.
• Subjects with active established RA currently receiving methotrexate (MTX), must have received it for at least 12 weeks, and at a stable dose (≥15mg/week) for at least 6 weeks prior to screening. They must be biologic drug naïve. These subjects must receive at least 5 mg oral folic acid weekly.
• Subjects diagnosed with RA must be seropositive with documented rheumatoid factor (RF) or anti-cyclic citrullinated peptide (anti CCP) positivity. If a documented history of RF or anti CCP positivity is not available, RF and anti CCP titers will be obtained at screening Group 3
• Healthy subjects without RA.
• All subjects must have sitting diastolic BP ≤90 mm Hg and/or sitting systolic BP ≤ 140 at screening
• Subjects must have fasting plasma glucose (FPG) of ≤ 100 mg/dL.
• If subjects with established RA are receiving an oral corticosteroid, the dose must be ≤7 mg/day prednisone (or equivalent) and stable for at least 28 days prior to screening.
• Subjects able and willing to give written informed consent and comply with the requirements of the study protocol. Informed consent must be obtained prior to any study-related procedures.
• A copy of the signed informed consent form must be given to the subject
• Patients must have a BMI of less than 42

You may not qualify if:

• Major surgery (including joint surgery) within 8 weeks prior to screening.
• Rheumatic autoimmune disease other than RA, including systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), scleroderma, polymyositis, or significant systemic involvement secondary to RA (vasculitis, pulmonary fibrosis or Felty's syndrome). Prior history of or current inflammatory joint disease other than RA (gout, Lyme disease, seronegative spondyloarthropathy including reactive arthritis and psoriatic arthritis)
• Functional class IV as defined by ACR Classification of Functional Status in RA
• Treatment with any investigational agent within 4 weeks (or 5 half-lives of investigational agent, whichever is longer) before screening
• Exposure to any Biologic Response Modifying Agent for RA
• Intraarticular or parenteral corticosteroids within 6 weeks prior to screening (For subjects with established RA)
• Smokers (use of tobacco products in the recent past \< 6 months). Urine cotinine levels will be measured during screening for all subjects. Smokers will be defined as any subject who reports cigarette use or has a urine cotinine greater than 200 ng/mL.
• Pregnant women or nursing mothers
• Females of child bearing potential who are not using reliable means of contraception
• Evidence of serious uncontrolled concomitant cardiovascular (including known CAD, HTN, or hyperlipidemia), nervous system, pulmonary, renal, hepatic, endocrine or GI disease.
• Uncontrolled disease states, such as asthma, psoriasis, or inflammatory bowel syndrome, where flares are commonly treated with corticosteroids.
• History or presence of severe bronchospastic disease (including asthma and chronic obstructive pulmonary disease, treated or not treated).
• History of cardiovascular abnormalities including myocardial infarction, angina pectoris, hypertensive encephalopathy, stroke, transient ischemic attack, valvular heart disease, ventricular arrhythmia A-V block, atrial fibrillation or cardiac revascularization/angioplasty. Symptoms or clinical evidence of congestive heart failure or known left ventricular ejection fraction \< 40%.
• Medical history of clinically significant ECG abnormalities, including history of a prolonged QT-interval syndrome.
• History of autonomic dysfunction

Sponsors & Collaborators

• Orrin M Troum, M.D. and Medical Associates: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Orrin M. Troum, MD and Medical Associates

Santa Monica, California, 90404, United States

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Orrin M Troum, MD

  Orrin M. Troum, MD and Medical Associates

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2011
• First Posted: December 26, 2011
• Study Start: December 1, 2011
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: May 8, 2013

Record last verified: 2013-05

Locations

US (1)