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

Purpose

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.
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).
To assess the clinical efficacy of Golimumab in Chinese Ankylosing Spondylitis(AS) patients according to ASAS response criteria at month 3, 6 and 12.
To perform cost-effectiveness and cost-utility analyses of the Golimumab in Ankylosing Spondylitis(AS) patients, using clinic-base data.

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

Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	Effect of Anti-TNF(Alpha)Treatment on Circulating Endothelial Progenitor Cells (EPCs) and Vascular Stiffness in AS

Resource links provided by NLM:

Genetics Home Reference related topics: ankylosing spondylitis

MedlinePlus related topics: Ankylosing Spondylitis

Drug Information available for: Sodium chloride Chlorine Golimumab

U.S. FDA Resources

Further study details as provided by Chinese University of Hong Kong:

Primary Outcome Measures:

Effect of Golimumab treatment on the progression of subclinical atherosclerosis [ Time Frame: Month 12 ] [ Designated as safety issue: Yes ]
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:

Effect of Golimumab treatment on the changes in arterial stiffness [ Time Frame: Month 12 ] [ Designated as safety issue: Yes ]
Effect of Golimumab on changes in arterial stiffness at 12 months compared with baseline as evaluated by Pulse Wave Velocity and Augmentation Index.
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 ] [ Designated as safety issue: Yes ]
The number and function of EPCs before and after golimumab will be assessed using Wilcoxin-sign rank test
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 ] [ Designated as safety issue: Yes ]
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
Incremental cost-utility ratio of the treatment of Golimumab. [ Time Frame: Month 12 ] [ Designated as safety issue: Yes ]
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.

Enrollment:	50
Study Start Date:	October 2010
Estimated Study Completion Date:	June 2013
Estimated Primary Completion Date:	June 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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 Other Name: 0.9ml sodium chloride

Arms

Assigned Interventions

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

Other Name: 0.9ml sodium chloride

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

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: 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

More Information

No publications provided

Responsible Party:	Lai-Shan Tam, Professor, Chinese University of Hong Kong
ClinicalTrials.gov Identifier:	NCT01212653 History of Changes
Other Study ID Numbers:	AS_2010
Study First Received:	September 30, 2010
Last Updated:	July 31, 2012
Health Authority:	Hong Kong: Joint CUHK-NTEC Clinical Research Ethics Committee

Keywords provided by 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

ClinicalTrials.gov processed this record on May 23, 2013