Condition category
Musculoskeletal Diseases
Date applied
01/02/2008
Date assigned
14/02/2008
Last edited
16/02/2015
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Bruce Kirkham

ORCID ID

Contact details

Rheumatology Department
Guy's Hospital
London
SE1 9RT
United Kingdom
+44 (0)207 188 5884
bruce.kirkham@gstt.nhs.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

RJ1 04/0027

Study information

Scientific title

Modification of vascular disease markers in active rheumatoid arthritis with fully human monoclonal anti-TNF-alpha antibody (Humira® [adalimumab])

Acronym

Marvel

Study hypothesis

The primary objective of the study is that measures of vascular dysfunction measured by flow mediated dilatation and pulse wave velocity and analysis, will improve after 13 weeks of adalimumab treatment.

Ethics approval

Guy's Hospital Research Ethics Committee, ref: 2004/01/06

Study design

Longitudinal single-centre open-label observational study

Primary study design

Observational

Secondary study design

Longitudinal

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Rheumatoid arthritis

Intervention

All participants under observation receive 40 mg adalimumab subcutaneously every other week (This trial investigates the changes in outcomes below from baseline).

Intervention type

Drug

Phase

Not Applicable

Drug names

Humira® (adalimumab)

Primary outcome measures

The following will be assessed pre-therapy and at week 0 (i.e. twice pre-therapy), then weeks 13 and 25:
1. Flow-mediated dilatation
2. Pulse wave velocity
3. Pulse wave analysis

Secondary outcome measures

1. Vascular remodeling assessed by carotid artery ultrasound after 25 weeks of treatment
2. Serum risk factors of vascular disease: Fasting lipids, Low Density Lipoprotein (LDL) subclasses, homocysteine, Homeostasis Model Assessment (HOMA) assessment for insulin resistance, Heat Shock Proteins (HSPs), and BiP (immunoglobulin binding protein), assessed pre-therapy and at week 0 (i.e. twice pre-therapy), then weeks 13 and 25
3. Measures of activated endothelial cell activity: Soluble InterCellular Adhesion Molecule (ICAM) and Vascular Cell Adhesion Molecule (VCAM), assessed pre-therapy and at week 0(i.e. twice pre-therapy), then weeks 13 and 25

Overall trial start date

01/09/2004

Overall trial end date

30/09/2008

Reason abandoned

Eligibility

Participant inclusion criteria

1. Subjects who fulfill the British Society of Rheumatology guidelines for TNF blocking therapy in Rheumatoid Arthritis (RA)
2. Subjects who have abnormal vascular function as assessed at the screening visit
3. Men and women >= 18 years of age, with RA as defined by the 1987-revised merican College of Rheumatology (ACR) diagnostic criteria, with a Disease Activity Score (DAS) greater than 5.1
4. Men and women of childbearing potential must use adequate birth control measures (e.g., abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, or surgical sterilization) for the duration of the study
5. Patient must be able to adhere to the study visit schedule
6. The patient must be capable of giving informed consent and the consent must be obtained prior to any screening procedures
7. Must have a chest X-ray within 3 months prior to commencement of adalimumab with no evidence of malignancy, infection or fibrosis

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

24

Participant exclusion criteria

1. Women who are pregnant or breast feeding.
2. Use of any investigational drug within 1 month prior to screening or within 5 half-lives of the investigational agent, whichever is longer.
3. Treatment with any other therapeutic agent targeted at reducing TNF (e.g., pentoxifylline, thalidomide, etanercept, etc.) within 3 months of screening.
4. History of diabetes mellitus.
5. History of ischemic heart disease or peripheral vascular disease.
6. Serious infections (such as pneumonia or pyelonephritis) in the previous 3 months. Less serious infections (such as acute upper respiratory tract infection [colds] or simple urinary tract infection) need not be considered exclusions at the discretion of the investigator.
7. Have active TB or have evidence of latent TB (old or latent TB on chest x-ray, without adequate therapy for TB initiated prior to first dose of study drug). Also excluded are patients with evidence of an old or latent TB infection without documented adequate therapy. Patients with a current close contact with an individual with active TB and patients who have completed treatment for active TB within the previous 2 years are explicitly excluded from the trial. Patients with a household member who has a history of active pulmonary TB should have had a thorough evaluation for TB prior to study enrollment as recommended by a local infectious disease specialist or published local guidelines of TB control agencies.
8. Presence of a transplanted organ (with the exception of a corneal transplant >3 months prior to screening).
9. Malignancy within the past 5 years (except for squamous or basal cell carcinoma of the skin that has been treated with no evidence of recurrence).
10. History of lymphoproliferative disease including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy of unusual size or location (such as nodes in the posterior triangle of the neck, infra-clavicular, epitrochlear, or periaortic areas), or splenomegaly.
11. Known recent substance abuse (drug or alcohol).
12. Poor tolerability of venepuncture required for blood sampling during the study period.

Recruitment start date

01/09/2004

Recruitment end date

30/09/2008

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Guy's Hospital
London
SE1 9RT
United Kingdom

Sponsor information

Organisation

Guy's and St Thomas' NHS Foundation Trust (UK)

Sponsor details

St Thomas' Street
London
SE1 9RT
United Kingdom
+44 (0)207 188 8888
bruce.kirkham@gstt.nhs.uk

Sponsor type

Government

Website

http://www.guysandstthomas.nhs.uk

Funders

Funder type

Industry

Funder name

Abbott UK

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes