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

NCT ID: NCT01212653

Last Updated: 2014-09-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-10-31
• Study Completion Date: 2013-05-31

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.

Conditions

Ankylosing Spondylitis(AS)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Simponi

Intervention Type: DRUG

Golimumab 50mg monthly

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.

Group Type: PLACEBO_COMPARATOR

0.9ml sodium chloride

Intervention Type: OTHER

0.9ml sodium chloride

Interventions

Simponi

Golimumab 50mg monthly

Intervention Type: DRUG

0.9ml sodium chloride

0.9ml sodium chloride

Intervention Type: OTHER

Other Intervention Names

Golimumab

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chinese University of Hong Kong

OTHER

Sponsor Role: lead

Responsible Party

Lai-Shan Tam

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Lai Shan Tam, MD

Role: PRINCIPAL_INVESTIGATOR

Chinese University of Hong Kong

Locations

Prince of Wales Hospital

Hong Kong, , China

Countries

China

References

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.

Reference Type: DERIVED

PMID: 24501241 (View on PubMed)

Other Identifiers

AS_2010

Identifier Type: -

Identifier Source: org_study_id