To investigate whether statin treatment can prevent or delay the development of RA in persons at increased risk of RA.
ID
Source
Brief title
Condition
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The development of arthritis (*1 swollen joint) is the primary outcome measure.
Secondary outcome
Serum lipids, calculated 10-year risk of cardiovascular events (in participants
aged 40 years and over), changes in cIMT and arterial stiffness are secondary
outcome measures.
Background summary
Rheumatoid arthritis (RA) affects the joints and can lead to serious
disability. In RA, a preclinical phase is often present, in which patients do
not have arthritis, but do exhibit specific antibodies, often accompanied by
vague joint symptoms and general symptoms. The existence of an at-risk phase
enables us to investigate interventions with the goal of preventing the
development of RA.
One of the major complications of RA is cardiovascular (CV) disease, which is
doubled in comparison to the general population. Inflammation is thought to
play an important role in this increased risk. Dyslipidaemia is also present,
many years before RA becomes clinically apparent.
Therefore, we hypothesize that statin therapy, due to its combined
lipid-lowering and anti-inflammatory effects, may be able to prevent the
development of RA in persons at increased risk for RA.
Study objective
To investigate whether statin treatment can prevent or delay the development of
RA in persons at increased risk of RA.
Study design
Multicenter double-blind randomized placebo-controlled trial.
Intervention
Atorvastatin 40 mg or placebo OD will be given to 110 seropositive arthralgia
patients in each arm during three years.
Study burden and risks
Participants will be evaluated before initiation of therapy or placebo, every 3
months thereafter in the first year and every 6 months thereafter until a total
of three years, with additional consultations by telephone at the three-month
time points in between. At all visits there will be a questionnaire and
physical examination (including a 44 joint examination). At each visit there
will be drug dispension, and check of adverse events and compliance of drug
therapy (pill count). Additional blood collection and carotid ultrasonography
(cIMT arterial stiffness measurements) will be performed each year in Reade and
in a part of the participating centers (at 0, 12, 24, and 36 months and the
ultrasonography at 0 and 36 months).
Dr. Jan van Breemenstraat 4
Amsterdam 1040KB
NL
Dr. Jan van Breemenstraat 4
Amsterdam 1040KB
NL
Listed location countries
Age
Inclusion criteria
1) Age ><= 18 years
2) Seropositive
-IgM-RF and ACPA positive OR
-High ACPA titer (>3x cut-off)
3) With or without current joint pain, but without current clinical synovitis (ultrasound exam should not be performed in case of doubt, since US was shown to be often false-positive in this patient group)
4) Written informed consent
Exclusion criteria
1) Patients with synovitis during clinical examination (any of 44 joints of DAS) at inclusion or synovitis in the past during clinical examination by a rheumatologist.
2) Patients with typical RA erosions on X-rays of hand and feet.
3) In case of inclusion depending on the presence of RF, the presence of situations with possible false-positive RF:known active infection with hepatitis C or Ebstein-Barr virus or recent radiotherapy.
4) Use of statins or other lipid-lowering agents within the last three months.
5) A history of previous use of statins discontinued due to side effects.
6) Patients with an indication for statin therapy according to local guidelines. All patients will be screened pior to randomisation
7) Previous use of DMARDs other than hydroxychloroquine, or use of hydroxychloroquine within the last three months.
8) A history of oral or parenteral use of corticosteroids within the last 12 weeks used to treat the current episode of musculoskeletal symptoms.
9) Subjects with current severe, progressive, or uncontrolled, hematologic disease, gastrointestinal disease, (diabetes with a serum glucose >7.0 mmol/L), pulmonary, cardiac, neurologic, or cerebral disease.
10) Subjects who are pregnant or who are breastfeeding or wish to become pregnant.
11) Subjects who currently abuse recreational drugs
12) Subjects who have a limited life expectancy.
13) Subjects who are unable to fill out the questionnaires.
14) Subjects who are using ciclosporin (which interacts with statins).
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-005524-42-NL |
| CCMO | NL47550.048.13 |
| OMON | NL-OMON19910 |