Official Title
Identification of Disease Susceptibility Genes Associated With Development and Clinical Characteristics of Primary Inflammatory Muscle Diseases, PM, DM and IBM.
Brief Title
Investigating Genes in Patients With Polymyositis and Dermatomyositis
Protocol ID
NCT01171573
Lead Sponsor
Northern Care Alliance NHS Foundation Trust
Brief Summary
Polymyositis (PM), dermatomyositis (DM) and inclusion body myositis (IBM)belong to a
group of inflammatory muscle disorders, of unknown cause, that are characterised by
skeletal muscle inflammation and progressive muscular weakness, which can be debilitating
and chronic in nature (occasionally fatal).
The current treatment options for these conditions are steroids and various other
immunosuppressive drugs. However, these are usually only partially effective at reducing
symptoms, and their toxic side effects also limit their usefulness. In order to develop
more specific treatments for myositis in the future (and therefore more effective), it is
important to understand the exact mechanisms that cause the disease in the first
instance. In other similar inflammatory diseases such as rheumatoid arthritis (RA) and
systemic lupus (SLE), it is known that changes to the Human Leukocyte Antigen(HLA), as
well as certain inflammatory cytokines, are involved in both the development and
expression of the disease.
As many of the inflammatory mechanisms that cause damage in PM, DM and IBM are similar to
those in RA and SLE, it seems likely that similar genetic factors will also be involved
in the development and expression of PM, DM and IBM.
In order to understand the genetic aspects / causes of myositis, and ultimately develop
more effective treatment therapies in the future, patients with PM, DM or IBM, will be
asked to give 20 mls of blood. These blood samples, along with the patient's clinical
details, will then be sent to the Centre for Integrated Genomic Medical Research (CIGMR),
at The University of Manchester, where all of the genetic analyses will take place. By
understanding the genetic cause of the disease, it should be possible to design specific
drugs for treating the condition in the future.
Detailed Description
In order to understand the genetic aspects / causes of myositis, and ultimately develop
more effective treatment therapies, it will be necessary to collect blood samples and
clinical details from around 1000 patients with myositis. As the condition is very rare,
it will not be possible to get the required number of patients from one centre alone, and
therefore, a collaborative, multicentred approach will be needed. Consultant
rheumatologists and neurologists throughout the UK, who have patients with PM, DM or IBM,
will be approached, and asked if they would like to officially enter into the myositis
genomic multicentred study. Once ethical and R&D approval has been granted, consultants
will be named as the 'Principal Investigators' at each of these 'research sites' and
could then start to recruit suitable patients into the study.
Patients from each research site, with definite PM, DM or IBM, will be asked by their own
consultants (Principal Investigator) to give 20 mls of blood via venepuncture for genetic
and antibody analysis. The PI will also complete a clinical/laboratory proforma, for each
patient, regarding their disease characteristics, to allow subsequent confirmation that
patients' disease is indeed definite, and this proforma and the blood sample will be sent
to CIGMR. All of the genetic analyses, will take place at CIGMR, but storage of clinical
details and certain patient identifiers will be stored at SRFT on a password protected
NHS tust computer.
This study will be co-ordinated by Dr RG Cooper through the Rheumatic Diseases Centre,
Salford Royal NHS Foundation Trust (SRFT), and Professor Bill Ollier from the Centre for
Integrated Genomic Medical Research unit (CIGMR), Stopford Building, Manchester
University.
Enrollment Count
1,000 participants
Eligibility Criteria
Inclusion Criteria:
Cases must fulfil Bohan and Peter Diagnostic Criteria for Adult PM/DM
1. Symmetrical weakness of limb-girdle muscles and/or anterior neck flexors.
2. Muscle biopsy evidence typical of myositis.
3. Elevation of serum skeletal muscle enzymes.
4. Typical EMG features of myositis.
5. Typical DM rash, including:
Probable / definite PM: at least 3 of items 1-4 +ive. Probable / definite DM: item 5 & at
least 2 of items 1-4 +ive.
Exclusion Criteria:
- Patients below the age of 18 years
- Patients with myositis secondary to alcohol or drug abuse, non abusive drug
ingestion (e.g with statins, fibrates etc)
- Patients with myositis following a recent viral illnesses.
- Patients unable to consent for themselves due to diminished mental capacity
- Patients that can not speak sufficiently good English.
- Patients unwilling to give blood sample.
Filters
Myositis
ACTIVE_NOT_RECRUITING
ADULT
OLDER_ADULT