UKMYONET: Investigating Genes in Patients With Polymyositis and Dermatomyositis

Sponsor

Northern Care Alliance NHS Foundation Trust (Other)

Overall Status

Recruiting

CT.gov ID

NCT01171573

Collaborator

(none)

1,000

Enrollment

Location

359

Duration (Months)

2.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Myositis	Procedure: Venepuncture

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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

1000 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

Identification of Disease Susceptibility Genes Associated With Development and Clinical Characteristics of Primary Inflammatory Muscle Diseases, PM, DM and IBM.

Study Start Date :

Jan 1, 2001

Anticipated Primary Completion Date :

Dec 1, 2030

Anticipated Study Completion Date :

Dec 1, 2030

Arms and Interventions

Arm	Intervention/Treatment
Myositis Patients Cases with myositis PM DM IBM Venepuncture	Procedure: Venepuncture Venepuncture - Taking blood
Healthy controls Control	Procedure: Venepuncture Venepuncture - Taking blood

Arm

Intervention/Treatment

Myositis Patients

Cases with myositis PM DM IBM Venepuncture

Procedure: Venepuncture

Venepuncture - Taking blood

Healthy controls

Control

Procedure: Venepuncture

Venepuncture - Taking blood

Outcome Measures

Primary Outcome Measures

To identify any disease susceptibility genes associated with development and clinical characteristics of primary inflammatory muscle diseases, PM, DM and IBM. [20 years]
Blood sample, DNA analysis, along with clinical data, matching genotype with phenotype

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Cases must fulfil Bohan and Peter Diagnostic Criteria for Adult PM/DM

Symmetrical weakness of limb-girdle muscles and/or anterior neck flexors.
Muscle biopsy evidence typical of myositis.
Elevation of serum skeletal muscle enzymes.
Typical EMG features of myositis.
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.