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

Plain English Summary

Not provided at time of registration

Study website

Type

Scientific

Contact name

Dr C.A. Wijbrandts

ORCID ID

Contact details

Academic Medical Centre (AMC)
Department of Medicine
Division of Clinical Immunology and Rheumatology
F4-218
P.O. Box 22660
Amsterdam
1100 DD
Netherlands
+31 (0)20 566 2171
c.a.wijbrandts@amc.uva.nl

EudraCT/CTIS number

IRAS number

ClinicalTrials.gov number

Protocol/serial number

N/A

Scientific title

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

Acronym

Study hypothesis

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).

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

Patient information sheet

Condition

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

Overall study end date

01/09/2006

Reason abandoned (if study stopped)

Participant 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

Participant type(s)

Patient

Age group

Adult

Lower age limit

18 Years

Sex

Not Specified

Target number of participants

20

Participant 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

Recruitment start date

01/10/2003

Recruitment end date

01/09/2006

Countries of recruitment

Netherlands

Study participating centre

Academic Medical Centre (AMC)
Amsterdam
1100 DD
Netherlands

Organisation

Academic Medical Centre (AMC) (The Netherlands)

Sponsor details

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

Sponsor type

Hospital/treatment centre

Website

http://www.amc.uva.nl/

ROR

https://ror.org/03t4gr691

Funder type

Industry

Funder name

Centocor Inc. (USA)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Individual participant data (IPD) sharing plan

IPD sharing plan summary

Not provided at time of registration

Study outputs