Hypothesis generating study to identify the changes in synovial tissue early after initiation of infliximab therapy

• Register: ISRCTN
• Last refreshed on: 18 October 2021
• Main ID: ISRCTN20710193
• Date of registration: 23/08/2007
• Prospective Registration: No
• Primary sponsor: Academic Medical Centre (AMC) (The Netherlands)
• Public title: Hypothesis generating study to identify the changes in synovial tissue early after initiation of infliximab therapy
• Scientific title: Hypothesis generating study to identify the changes in synovial tissue early after initiation of infliximab therapy
• Date of first enrolment: 01/10/2003
• Target sample size: 20
• Recruitment status: Completed
• URL: https://www.isrctn.com/ISRCTN20710193
• Study type: Interventional
• Study design: Non-randomised, non-controlled, exploratory study (Treatment)
• Phase: Not Specified

Countries of recruitment

Netherlands

Contacts

• Name: C.A. Wijbrandts

Key inclusion & exclusion criteria

Inclusion criteria:
1. Rheumatoid Arthritis (RA) patients with active disease at baseline assessed by the Disease Activity Score (DAS-28)
2. Be more than or equal to 18 years of age
3. Use concurrent methotrexate treatment (7.5 - 30 mg/week; stable since greater than or equal to 28 days before initiation) during the study. Subjects may be taking non-steroidal anti-inflammatory drugs, provided the dose and frequency have been stable for at least 28 days. Subjects may be receiving prednisone therapy less than or equal to 10 mg/day provided that the dosage has been stable for at least a months prior to entry

Exclusion criteria:
1. Pregnancy
2. Breastfeeding
3. A history of or acute inflammatory joint disease of different origin, e.g., mixed connective tissue disease, seronegative spondyloarthropathy, psoriatic arthritis, Reiter's syndrome, systemic lupus erythematosus or any arthritis with onset prior to age 16 years
4. Acute major trauma
5. Previous therapy at any time with:
5.1. TNF-directed monoclonal antibodies
5.2. p75 TNF receptor fusion protein
6. Therapy within the previous 45 days with:
6.1. Any experimental drug
6.2. Alkylating agents, e.g. cyclophosphamide, chlorambucil
6.3. Anti-metabolites
6.4. Monoclonal antibodies
6.5. Growth factors
6.6. Other cytokines
7. Therapy within the previous 28 days with:
7.1. Parenteral or intraarticular corticoid injections
7.2. Oral corticosteroid therapy exceeding a prednisone equivalent of 10 mg daily
7.3. Present use of Disease Modifying Anti-Rheumatic Drugs (DMARDs) other than methotrexate
8. Fever (orally measured greater than 38°C), chronic infections or infections requiring anti-microbial therapy
9. Manifest cardiac failure (stage III or IV according to New York Heart Association [NYHA] classification)
10. Progressive fatal disease/terminal illness
11. A hematopoietic disease
12. Body weight of less than 45 kg


Age minimum:
Age maximum:
Gender: Not Specified

Health Condition(s) or Problem(s) studied

Rheumatoid arthritis
Musculoskeletal Diseases
Arthropathies

Intervention(s)

Infliximab therapy (3 mg/kg intravenous [i.v.]) according to the normal regimen. At baseline and 1 hour (n = 5) or 24 hours (n = 5) after the first infliximab infusion synovial biopsies were obtained from an inflamed knee joint. Peripheral blood mononuclear cells were obtained before and 1 and 24 hours after infliximab infusion in 20 patients (10 only blood, 10 with paired synovial biopsies). Serum was drawn at similar timepoints.

Primary Outcome(s)

1. Primary immunohistological outcome: detection of apoptosis in synovial tissue within 1 or 24 hours after initiation of treatment. Analysis by immunohistochemical staining and electron microscopy
2. Primary serological outcome: To determine whether TNF targeted therapy with infliximab results in apoptosis of peripheral blood mononuclear cells within 1 or 24 hours after initiation of treatment

Secondary Outcome(s)

To determine whether TNF targeted therapy with infliximab results in decreased synovial cellularity.

Secondary ID(s)

N/A

Source(s) of Monetary Support

Centocor Inc. (USA)

Ethics review

Status:
Approval date:
Contact:

Ethics approval received from the Medical ethical committee of the Academic Medical Center/University of Amsterdam on the 1st October 2003 (ref: MEC 01/086).

Results

• Results available: Yes
• Date Completed: 01/09/2006