Endothelial Function, Inflammatory Disease Activity, and Bone and Cartilage Markers in Rheumatic Patients: The Influence of Antirheumatic Treatment (PSARA)

• ClinicalTrials.gov Identifier: NCT00902005
• Recruitment Status: Completed
• First Posted: May 14, 2009
• Last Update Posted: November 21, 2013
• Sponsor: Revmatismesykehuset AS
• Collaborator: Abbott
• Information provided by (Responsible Party): Revmatismesykehuset AS

Study Description

Brief Summary:

The aim of this study is to examine the associations between inflammatory disease activity and endothelial function in rheumatoid arthritis (RA) and spondyloarthritis patients treated with methotrexate and Tumor Necrosis Factor alpha (TNFalpha)inhibitor in combination or methotrexate or TNFalpha-inhibitor alone. Further, to look for improvement in endothelial function, and decrease in bone and cartilage destruction during treatment with the combination therapy of TNFalpha-inhibitor and methotrexate in RA and Psoriatic Arthritis (PSA) patients. Last, examine the TNFalpha inhibitors influence on endothelial function and levels of bone and cartilage markers in patients with Ankylosing Spondylitis (AS).

Condition or disease
Rheumatoid Arthritis; Psoriatic Arthritis; Ankylosing Spondylitis; Endothelial Dysfunction; Inflammatory Disease Activity

Study Design

• Study Type: Observational
• Actual Enrollment: 145 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Endothelial Function, Inflammatory Disease Activity, and Bone and Cartilage Markers in RA and Spondyloarthritis Patients, Treated With TNFalpha-inhibitors in Combination With Methotrexate or Methotrexate or TNFalpha-inhibitors Alone - a Prospective Study
• Study Start Date: April 2008
• Actual Primary Completion Date: June 2011
• Actual Study Completion Date: August 2012

Groups and Cohorts

Group/Cohort
Rheumatic patients; Three groups: RA patients: 30 starting on Methotrexate, 30 starting on combination of Methotrexate and TNFalpha inhibitor. PSA patients: 20 starting on Methotrexate, 20 starting on combination of Methotrexate and TNFalpha inhibitor. AS patients: 20 starting on TNFalpha inhibitor

Outcome Measures

Primary Outcome Measures :

1. To examine the association between inflammatory disease activity and endothelial function in RA and spondyloarthritis patients treated with methotrexate and TNFalpha-inhibitor in combination or methotrexate or TNFalpha-inhibitor alone [ Time Frame: Baseline (before treatment starts), 6 weeks and 6 months after starting treatment ]

Secondary Outcome Measures :

1. CRP (C-reactive protein) [ Time Frame: Baseline (before starting treatment), 6 weeks, 6 months after starting treatment ]
2. DAS28 (Disease activity score) [ Time Frame: Baseline (before starting treatment), 6 weeks, 6 months after starting treatment ]
3. COMP (cartilage oligomeric matrix protein 1) [ Time Frame: Baseline (before starting treatment), 6 weeks, 6 months after starting treatment ]
4. IL-6 (interleukin 6) [ Time Frame: Baseline (before starting treatment), 6 weeks, 6 months after starting treatment ]
5. s-RAGE (Receptor of Advanced Glycation End products) [ Time Frame: Baseline (before starting treatment), 6 weeks, 6 months after starting treatment ]

Biospecimen Retention:   Samples With DNA

Whole blood

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Patients with RA and spondyloarthritis starting with either combination therapy of TNFalpha-inhibitor and methotrexate or methotrexate or TNFalpha-inhibitor alone, at Lillehammer Hospital for Rheumatic diseases.Decision about treatment modality will be based on conventional clinial judgement.

Criteria

Inclusion Criteria:

• Males and females 18-80 years
• Able and willing to give written informed consent, and to comply with the requirements of the study protocol.
• Fulfilling the ACR 1987 revised diagnostic criteria for the diagnosis rheumatoid arthritis, or the diagnostic criteria by Moll and Wright for the diagnosis psoriatic arthritis, or the modified New York diagnostic criteria for ankylosing spondylitis.
• Clinical indication for starting treatment with methotrexate, TNFalpha- inhibitor or combination therapy.
• Use of reliable method of contraception for women with childbearing potential.

Exclusion Criteria:

• Lack of cooperativity
• Positive serology for hepatitis B or C
• History of positive HIV status.
• History of tuberculosis or untreated tuberculosis.
• PPD more than 15 mm in previously BCG immunized subjects. PPD 6 mm or more if not previously BCG immunized.
• Histoplasmosis or Listeriosis
• Persistent or recurrent infections
• Any inflammatory disease of permanence not related to RA, PSA or AS.
• Pregnancy or breast-feeding.
• Use of prednisolone more than 10 mg daily for 2 weeks at inclusion.
• Use of TNFalpha-inhibitor the last 4 weeks.
• History of cancer.
• Uncontrolled diabetes.
• Congestive heart failure (Nyha 3-4)
• Recent stroke (within 3 months)
• Previous diagnosis or signs of central nervous system demyelinating disease.
• Previously diagnosed immunodeficiency.

Contacts and Locations

Locations

Norway

Lillehammer Hospital for Rheumatic Diseases

Lillehammer, Oppland, Norway, 2609

Sponsors and Collaborators

Revmatismesykehuset AS

Abbott

Investigators

• Study Chair: Knut Mikkelsen, MD; Lillehammer Hospital for Rheumatic Diseases
• Principal Investigator: Gunnbjørg Hjeltnes, MD; Lillehammer Hospital for Rheumatic Diseases

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Hokstad I, Deyab G, Wang Fagerland M, Lyberg T, Hjeltnes G, Forre O, Agewall S, Mollnes TE, Hollan I. Tumor necrosis factor inhibitors are associated with reduced complement activation in spondylarthropathies: An observational study. PLoS One. 2019 Jul 23;14(7):e0220079. doi: 10.1371/journal.pone.0220079. eCollection 2019.

Deyab G, Hokstad I, Whist JE, Smastuen MC, Agewall S, Lyberg T, Ronda N, Mikkelsen K, Hjeltnes G, Hollan I. Methotrexate and anti-tumor necrosis factor treatment improves endothelial function in patients with inflammatory arthritis. Arthritis Res Ther. 2017 Oct 17;19(1):232. doi: 10.1186/s13075-017-1439-1.

Ronda N, Greco D, Adorni MP, Zimetti F, Favari E, Hjeltnes G, Mikkelsen K, Borghi MO, Favalli EG, Gatti R, Hollan I, Meroni PL, Bernini F. Newly identified antiatherosclerotic activity of methotrexate and adalimumab: complementary effects on lipoprotein function and macrophage cholesterol metabolism. Arthritis Rheumatol. 2015 May;67(5):1155-64. doi: 10.1002/art.39039.

Hjeltnes G, Hollan I, Forre O, Wiik A, Lyberg T, Mikkelsen K, Agewall S. Relations of serum COMP to cardiovascular risk factors and endothelial function in patients with rheumatoid arthritis treated with methotrexate and TNF-alpha inhibitors. J Rheumatol. 2012 Jul;39(7):1341-7. doi: 10.3899/jrheum.111401. Epub 2012 Jun 1.

• Responsible Party: Revmatismesykehuset AS
• ClinicalTrials.gov Identifier: NCT00902005
• Other Study ID Numbers: S-07377b
• First Posted: May 14, 2009
• Last Update Posted: November 21, 2013
• Last Verified: November 2013

Keywords provided by Revmatismesykehuset AS:

Endothelial dysfunction; Bone and cartilage markers; Inflammatory disease activity; Rheumatoid arthritis; Psoriatic arthritis; Ankylosing Spondylitis

Additional relevant MeSH terms:

Spondylitis; Arthritis; Arthritis, Rheumatoid; Arthritis, Psoriatic; Spondylarthritis; Spondylitis, Ankylosing; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Spondylarthropathies; Spinal Diseases; Bone Diseases; Psoriasis; Skin Diseases, Papulosquamous; Skin Diseases; Bone Diseases, Infectious; Infections; Ankylosis