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

Primary Purpose

Ankylosing Spondylitis(AS)

Status
Completed
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Simponi
0.9ml sodium chloride
Sponsored by
Chinese University of Hong Kong
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ankylosing Spondylitis(AS) focused on measuring Ankylosing Spondylitis, Golimumab, Simponi, Anti-TNF alpha, EPCs, Vascular stiffness

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Prince of Wales Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Golimumab

Pacebo-controlled

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Effect of Golimumab treatment on the progression of subclinical atherosclerosis
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
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.
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.
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.
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.

Full Information

First Posted
September 30, 2010
Last Updated
September 10, 2014
Sponsor
Chinese University of Hong Kong
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1. Study Identification

Unique Protocol Identification Number
NCT01212653
Brief Title
Effect of Anti-TNF (Alpha) Treatment on Vascular Stiffness in Ankylosing Spondylitis (AS)
Acronym
AS
Official Title
Effect of Anti-TNF(Alpha)Treatment on Circulating Endothelial Progenitor Cells (EPCs) and Vascular Stiffness in AS
Study Type
Interventional

2. Study Status

Record Verification Date
September 2014
Overall Recruitment Status
Completed
Study Start Date
October 2010 (undefined)
Primary Completion Date
May 2013 (Actual)
Study Completion Date
May 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Chinese University of Hong Kong

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ankylosing Spondylitis(AS)
Keywords
Ankylosing Spondylitis, Golimumab, Simponi, Anti-TNF alpha, EPCs, Vascular stiffness

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
50 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Golimumab
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Pacebo-controlled
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Simponi
Other Intervention Name(s)
Golimumab
Intervention Description
Golimumab 50mg monthly
Intervention Type
Other
Intervention Name(s)
0.9ml sodium chloride
Intervention Description
0.9ml sodium chloride
Primary Outcome Measure Information:
Title
Effect of Golimumab treatment on the progression of subclinical atherosclerosis
Description
Effect of Golimumab treatment on the progression of subclinical atherosclerosis at 12 months compared with baseline as evaluated by Intima-Media Thickness (IMT).
Time Frame
Month 12
Secondary Outcome Measure Information:
Title
Effect of Golimumab treatment on the changes in arterial stiffness
Description
Effect of Golimumab on changes in arterial stiffness at 12 months compared with baseline as evaluated by Pulse Wave Velocity and Augmentation Index.
Time Frame
Month 12
Title
Changes on the number and function of Endothelial Progenitor Cells in Ankylosing Spondylitis before and after 1 year of Golimumab compared with baseline.
Description
The number and function of EPCs before and after golimumab will be assessed using Wilcoxin-sign rank test
Time Frame
Month 12
Title
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.
Description
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
Time Frame
Month 12
Title
Incremental cost-utility ratio of the treatment of Golimumab.
Description
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.
Time Frame
Month 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lai Shan Tam, MD
Organizational Affiliation
Chinese University of Hong Kong
Official's Role
Principal Investigator
Facility Information:
Facility Name
Prince of Wales Hospital
City
Hong Kong
Country
China

12. IPD Sharing Statement

Citations:
PubMed Identifier
24501241
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.
Results Reference
derived

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

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