ClinicalTrials.gov
ClinicalTrials.gov Menu

Effect of Anti-TNF (Alpha) Treatment on Vascular Stiffness in Ankylosing Spondylitis (AS) (AS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01212653
Recruitment Status : Completed
First Posted : October 1, 2010
Last Update Posted : September 11, 2014
Sponsor:
Information provided by (Responsible Party):
Lai-Shan Tam, Chinese University of Hong Kong

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.

Condition or disease Intervention/treatment Phase
Ankylosing Spondylitis(AS) Drug: Simponi Other: 0.9ml sodium chloride Phase 4

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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Effect of Anti-TNF(Alpha)Treatment on Circulating Endothelial Progenitor Cells (EPCs) and Vascular Stiffness in AS
Study Start Date : October 2010
Actual Primary Completion Date : May 2013
Actual Study Completion Date : May 2013

Resource links provided by the National Library of Medicine

Drug Information available for: Golimumab

Arm Intervention/treatment
Active Comparator: Golimumab

In this 52-week, randomized, placebo-controlled study, patients will be randomized to receive either golimumab 50 mg monthly or matching placebo for 12 months using a 1:1 randomization procedure.

The doctors and patients and the nurse who administer the study medication (Golimumab) will be blinded. There will be one unblinded nurse to prepare the study medication.

Drug: Simponi
Golimumab 50mg monthly
Other Name: Golimumab

Placebo Comparator: Pacebo-controlled

In this 52-week, randomized, placebo-controlled study, patients will be randomized to receive either Golimumab 50 mg monthly or matching placebo for 12 months using a 1:1 randomization procedure.

The doctors and patients and the nurse who administer the study medication (Golimumab) will be blinded. There will be one unblinded nurse to prepare the study medication.

Other: 0.9ml sodium chloride
0.9ml sodium chloride




Primary Outcome Measures :
  1. Effect of Golimumab treatment on the progression of subclinical atherosclerosis [ Time Frame: Month 12 ]
    Effect of Golimumab treatment on the progression of subclinical atherosclerosis at 12 months compared with baseline as evaluated by Intima-Media Thickness (IMT).


Secondary Outcome Measures :
  1. Effect of Golimumab treatment on the changes in arterial stiffness [ Time Frame: Month 12 ]
    Effect of Golimumab on changes in arterial stiffness at 12 months compared with baseline as evaluated by Pulse Wave Velocity and Augmentation Index.

  2. Changes on the number and function of Endothelial Progenitor Cells in Ankylosing Spondylitis before and after 1 year of Golimumab compared with baseline. [ Time Frame: Month 12 ]
    The number and function of EPCs before and after golimumab will be assessed using Wilcoxin-sign rank test

  3. 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. [ Time Frame: Month 12 ]
    Correlation between the change in disease activity markers (BASDAI, ESR, CRP, and MRI global activity score) and the change in IMT, PWV and AIx and EPC number will be assessed using Spearman's test

  4. Incremental cost-utility ratio of the treatment of Golimumab. [ Time Frame: Month 12 ]
    Utility will be assessed using the EuroQol 5D (EQ5D) and the Short-Form 36 (SF-36), at baseline and every visit.Utility is used to calculate quality-adjusted life years (QALYs). The incremental cost-utility ratio expressed as "(annual costs of golimumab treatment - annual costs of placebo treatment) / additional QALY gain by golimumab treatment" is calculated.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01212653


Locations
China
Prince of Wales Hospital
Hong Kong, China
Sponsors and Collaborators
Chinese University of Hong Kong
Investigators
Principal Investigator: Lai Shan Tam, MD Chinese University of Hong Kong

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Lai-Shan Tam, Professor, Chinese University of Hong Kong
ClinicalTrials.gov Identifier: NCT01212653     History of Changes
Other Study ID Numbers: AS_2010
First Posted: October 1, 2010    Key Record Dates
Last Update Posted: September 11, 2014
Last Verified: September 2014

Keywords provided by Lai-Shan Tam, Chinese University of Hong Kong:
Ankylosing Spondylitis
Golimumab
Simponi
Anti-TNF alpha
EPCs
Vascular stiffness

Additional relevant MeSH terms:
Spondylitis
Spondylitis, Ankylosing
Bone Diseases, Infectious
Infection
Bone Diseases
Musculoskeletal Diseases
Spinal Diseases
Spondylarthropathies
Spondylarthritis
Ankylosis
Joint Diseases
Arthritis
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs