Clinical trial NCT01212653: Effect of Anti-TNF (Alpha) Treatment on Vascular Stiffness in Ankylosing Spondylitis (AS)
Official title: Effect of Anti-TNF(Alpha)Treatment on Circulating Endothelial Progenitor Cells (EPCs) and Vascular Stiffness in AS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Ankylosing Spondylitis(AS)
Keywords: Ankylosing Spondylitis
Golimumab
Simponi
Anti-TNF alpha
EPCs
Vascular stiffness
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
First posted: 2010-10-01
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 1. To determine the effect of Golimumab treatment on the number and function of Endothelial Progenitor Cells (EPCs) in Ankylosing Spondylitis(AS) patients as a possible mechanism for the effect of this treatment on endothelial function.
2. To ascertain the effect of Golimumab treatment on , carotid intima-media thickness, vascular stiffness in Ankylosing Spondylitis(AS) patients as measured by pulse wave velocity (PWV) and Augmentation index (AIx).
3. To assess the clinical efficacy of Golimumab in Chinese Ankylosing Spondylitis(AS) patients according to ASAS response criteria at month 3, 6 and 12.
4. To perform cost-effectiveness and cost-utility analyses of the Golimumab in Ankylosing Spondylitis(AS) patients, using clinic-base data.

Detailed description: This study will provide important data on the pathogenesis of vascular damage and possible mechanism by which potent anti-inflammatory treatment may reduce cardiovascular risk in Ankylosing Spondylitis(AS) patients.

Fifty patients with Ankylosing Spondylitis(AS) will be randomized to receive either Golimumab or Placebo for 12 months. Patients randomized to Placebo with worsening disease activity (failure to achieve Assessment of SpondyloArthritis international Society (ASAS20)) at week 24 will be permitted to escape to open-label Golimumab. Clinical assessment, intima-media thickness, vascular stiffness and endothelial progenitor cells will be performed at baseline, 6 and 12 months.

Eligibility criteria: Inclusion Criteria:

* Men or women, 18 years of age or older
* Fulfilled the modified New York diagnostic criteria for Ankylosing spondylitis (AS)for more than 3 months
* Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4 (0-10 point scale), Pain visual analog scale(VAS) ≥ 4 (0-10cm scale)
* Inadequate response to at least two Nonsteroidal Antiinflammatory Drugs (NASID) on highest recommended doses for 3 months or unable to receive full 3-month course because of intolerance,toxicity or contraindications
* Normal Chest X-ray within 3 months before baseline
* Purified Protein Derivative(PPD) negative, or Latent Tuberculosis (TB) patients were required therapy for Tuberculosis (TB) before or simultaneously with first dose of study agent

Exclusion Criteria:

* Complete ankylosis of the spine
* Concurrent with other inflammatory rheumatic disease
* Serious infection (treatment with IV-infective) within 2 months before randomization
* Active Tuberculosis (TB) or recent contact with a person with active Tuberculosis (TB)
* An opportunistic infection within 6 months of screening
* Known history of Hepatitis, Human Immunodeficiency Virus (HIV), Malignancy, a transplanted organ, multiple sclerosis, congestive heart failure
* Currently on systemic immunosuppressives, DMARDS (other than Methotrexate, Sulfasalazine , or Hydroxychloroquine), or Leflunomide within 4 week before first study agent
* Any previous use of Alefacept, Efalizumab, Rituximab, Golimumab or Natalizumab
* Use of cytotoxic drugs, received intra-articular, intramuscular, or intravenous corticosteroids in the past 4 weeks before screening
* Clinically significant renal disease (serum creatinine level ≥ 270µmol/L), alanine aminotransferase (ALT) ≥ 2 x upper limit of normal (ULN)
* Hemoglobin level \< 8.5gm/dl, a white blood cell count \< 3.5x 109/liter, a platelet count \< 100x 109/liter
* Female of childbearing potential, unwilling to use adequate contraception during the study
* Pregnant or breastfeeding women

Primary outcomes:
measure: Effect of Golimumab treatment on the progression of subclinical atherosclerosis
timeFrame: Month 12
Secondary outcomes:
measure: Effect of Golimumab treatment on the changes in arterial stiffness
timeFrame: Month 12
measure: Changes on the number and function of Endothelial Progenitor Cells in Ankylosing Spondylitis before and after 1 year of Golimumab compared with baseline.
timeFrame: Month 12
measure: To correlate the changes in Intima-Media Thickening, Pulse Wave Velocity, Augmentation Index and Endothelial Progenitor Cells with the changes in markers of disease activity.
timeFrame: Month 12
measure: Incremental cost-utility ratio of the treatment of Golimumab.
timeFrame: Month 12
Other outcomes:
Locations:
city: Hong Kong
country: China
facility: Prince of Wales Hospital
Study officials:
affiliation: Chinese University of Hong Kong
name: Lai Shan Tam, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tam LS, Shang Q, Kun EW, Lee KL, Yip ML, Li M, Li TK, Zhu TY, Pui MO, Li EK, Yu CM. The effects of golimumab on subclinical atherosclerosis and arterial stiffness in ankylosing spondylitis-a randomized, placebo-controlled pilot trial. Rheumatology (Oxford). 2014 Jun;53(6):1065-74. doi: 10.1093/rheumatology/ket469.