MARVEL: Modification by Adalimumab of Rheumatoid arthritis Vascular and EndotheLial function

ISRCTN	ISRCTN90051516
DOI	https://doi.org/10.1186/ISRCTN90051516
Secondary identifying numbers	RJ1 04/0027

Submission date: 01/02/2008
Registration date: 14/02/2008
Last edited: 07/06/2017

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

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Bruce Kirkham
Scientific

Rheumatology Department
Guy's Hospital
London
SE1 9RT
United Kingdom

Phone	+44 (0)207 188 5884
Email	bruce.kirkham@gstt.nhs.uk

Study information

Study design	Longitudinal single-centre open-label observational study
Primary study design	Observational
Secondary study design	Longitudinal
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
Scientific title	Modification of vascular disease markers in active rheumatoid arthritis with fully human monoclonal anti-TNF-alpha antibody (Humira® [adalimumab])
Study acronym	Marvel
Study objectives	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(s)	Guy's Hospital Research Ethics Committee, ref: 2004/01/06
Health condition(s) or problem(s) studied	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
Pharmaceutical study type(s)
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Humira® (adalimumab)
Primary outcome measure	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 study start date	01/09/2004
Completion date	30/09/2008

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	24
Key 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
Key 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.
Date of first enrolment	01/09/2004
Date of final enrolment	30/09/2008

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Guy's Hospital

London
SE1 9RT
United Kingdom

Sponsor information

Guy's and St Thomas' NHS Foundation Trust (UK)
Hospital/treatment centre

St Thomas' Street
London
SE1 9RT
England
United Kingdom

Phone	+44 (0)207 188 8888
Email	bruce.kirkham@gstt.nhs.uk
Website	http://www.guysandstthomas.nhs.uk
"ROR"	https://ror.org/00j161312

Funders

Funder type

Industry

Abbott UK

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

Editorial Notes

07/06/2017: No publications found in PubMed, verifying study status with principal investigator.