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

ISRCTN	ISRCTN20710193
DOI	https://doi.org/10.1186/ISRCTN20710193
Secondary identifying numbers	N/A

Submission date: 23/08/2007
Registration date: 23/08/2007
Last edited: 07/10/2021

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Musculoskeletal Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr C.A. Wijbrandts
Scientific

Academic Medical Centre (AMC)
Department of Medicine, Division of Clinical Immunology and Rheumatology, F4-218
P.O. Box 22660
Amsterdam
1100 DD
Netherlands

Phone	+31 (0)20 566 2171
Email	c.a.wijbrandts@amc.uva.nl

Study information

Study design	Non-randomised, non-controlled, exploratory study
Primary study design	Interventional
Secondary study design	Non randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Scientific title	Hypothesis generating study to identify the changes in synovial tissue early after initiation of infliximab therapy
Study objectives	Exploratory study to investigate the effects of Tumour Necrotising Factor (TNF) targeted therapy with infliximab on the synovial cell infiltrate, and the induction of apoptosis.
Ethics approval(s)	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).
Health condition(s) or problem(s) studied	Rheumatoid arthritis
Intervention	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.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Infliximab
Primary outcome measure	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 measures	To determine whether TNF targeted therapy with infliximab results in decreased synovial cellularity.
Overall study start date	01/10/2003
Completion date	01/09/2006

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Not Specified
Target number of participants	20
Key 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
Key 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
Date of first enrolment	01/10/2003
Date of final enrolment	01/09/2006

Locations

Countries of recruitment

Netherlands

Study participating centre

Academic Medical Centre (AMC)

Amsterdam
1100 DD
Netherlands

Sponsor information

Academic Medical Centre (AMC) (The Netherlands)
Hospital/treatment centre

Division of Clinical Immunology and Rheumatology
PO Box 22660
Amsterdam
1100 DD
Netherlands

Website	http://www.amc.uva.nl/
"ROR"	https://ror.org/03t4gr691

Funders

Funder type

Industry

Centocor Inc. (USA)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article		30/10/2008	07/10/2021	Yes	No

Editorial Notes

07/10/2021: Publication reference added.