MYOPROSP - a Prospective Cohort Study in Myositis (MYOPROSP)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02468895|
Recruitment Status : Recruiting
First Posted : June 11, 2015
Last Update Posted : February 1, 2017
|First Submitted Date||December 5, 2014|
|First Posted Date||June 11, 2015|
|Last Update Posted Date||February 1, 2017|
|Actual Start Date||October 4, 2016|
|Estimated Primary Completion Date||February 2021 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures
||Number of participants with a significant change levels of diagnostic biomarkers. [ Time Frame: 5 years ]
This will depend on the specific biomarker/cytokine being measured
|Original Primary Outcome Measures||Same as current|
|Change History||Complete list of historical versions of study NCT02468895 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures
|Original Secondary Outcome Measures||Same as current|
|Current Other Outcome Measures||Not Provided|
|Original Other Outcome Measures||Not Provided|
|Brief Title||MYOPROSP - a Prospective Cohort Study in Myositis|
|Official Title||MYOPROSP: A Prospective Cohort Study to Identify a Stratified Approach in the Diagnosis, Treatment and Delivery of Care in Adult Idiopathic Inflammatory Myopathy|
Adult patients with suspected or confirmed idiopathic inflammatory myopathy (IIM) will be recruited. Patients will be approached, consented, have baseline demographics, diagnostics and disease activity measures recorded, and blood taken. The collection of data and biological material will mirror usual clinical practice as far as possible. Subjects will ideally attend further visits at 3, 6 and 12 months to have bloods taken, outcome measures recorded and questionnaires completed.
In addition, blood, muscle biopsies and imaging undertaken as part of usual care will also be collected for research purposes to measure a number of biomarkers for the assessment of diagnostic accuracy and clinical utility evaluation. As per usual practice, a muscle biopsy will be performed at baseline, and a further biopsy offered at 6 months to assess treatment response. A magnetic resonance (MR) muscle protocol will also be performed as per usual clinical practice, and a gadolinium-enhanced MR heart scan offered. Both these scans will be repeated at 6 months. An existing electronic database entry system will be used for data entry and capture on an anonymised basis.
The study will thus be based around diagnostic evaluations and outcome measures to improve quality of care in IIM.
The bioresource from this protocol, ethics application and future funding will comprise the following:
i) UKMYONET cross-sectional study ii) MYOPROSP inception cohort study iii) MYOACT novel therapies registry iv) UK neuromuscular biobank
Primary endpoint The primary study endpoint will be sensitivity to change of the biomarkers of interest.
This will include but not limited to:
Cases will be adults >18 years, with a number of different IIM clinical phenotypes encountered in clinically practice. It is vitally important that patients with suspected, but not confirmed, IIM are also included so that the natural history and subsequent final diagnoses can be tracked. Subsequent investigations will often confirm a diagnosis that was not confirmed at initial presentation. Patients who do have confirmed PM/DM will have IIM according to the Bohan and Peter criteria, which remains the internationally accepted criteria for inclusion into clinical trials. Disease duration from onset of initial symptoms would ideally be less than one year to enrich the cohort with patients of high disease activity and minimal established disease-related damage.
Patients with suspected "possible" polymyositis (PM)/dermatomyositis (DM), where a diagnosis of IIM is suspected but not confirmed probable/definite by the Bohan and Peter criteria, will also be eligible. Patients with myositis as their primary condition and also fulfilling criteria for an associated connective tissue disease, including but not limited to, systemic sclerosis, Sjogren's, SLE, rheumatoid arthritis, will also be allowed for inclusion into the study. Patients will also be eligible if they present with ILD/Raynaud's or other CTD features in association with a myositis specific antibody other than an anti-synthetase and no other obvious IIM-diagnostic features. Patients with IBM will also be accepted on to the study, meeting the revised MRC Neuromuscular criteria.
Patients will also be accepted on to the study if they possess amyopathic or hypomyopathic DM, as per the Sontheimer criteria, which states that "amyopathic DM is a subset of DM characterized by biopsy-confirmed hallmark cutaneous manifestations of classic DM occurring for 6 months or longer with no clinical evidence of proximal muscle weakness and no serum muscle enzyme abnormalities. If more extensive muscle testing is carried out, the results should be within normal limits".
Initial approach Patients will be sent a letter from their consultants. The letter will give a brief introduction to the proposed study and a patient information sheet will be included. A unique identifier would be assigned to each potential new recruit. Potential participants will be given a full explanation of the study and provided with a patient information sheet and consent form to sign, following the opportunity to ask any questions. If having been allowed sufficient time to consider their decision, and they want to participate, informed consent will then be sought. The samples will be anonymised, processed, and sent to The University of Manchester for storage and analysis. No treatment will be withheld for the purposes of this study.
Data collection i) UKMYONET cross-sectional study Baseline core data encompassing the clinical information outlined in UKMYONET will be collected. Blood for sera and plasma will also be collected. Retrospective data collection will also be allowed to interrogate how baseline characteristics may influence outcome.
ii) MYOPROSP inception cohort study Baseline core data encompassing the clinical information outlined in UKMYONET will be collected, and extended data on medication use and disease activity. As genetic material (DNA) does not change with time, it would only be necessary to obtain this at one time-point (0 months); however, epigenetic, psychological, clinical and serological factors will alter over the course of the treatment, therefore sequential samples will be taken at 3, 6 and 12 month time points for comparison. Whilst being taken as part of routine clinical practice, patients can also consent to have part of their muscle biopsy, used for research purposes, as well as a follow-up biopsy. If other tissues are being taken as part of routine clinical practice, the patient can also be consented for their use as part of research studies. Patients may also be approached for further clinical data collection at yearly intervals up to 5 years after inception.
iii) MYOACT novel therapies registry Baseline core data encompassing the clinical information outlined in UKMYONET will be collected, and extended data on medication use and disease activity. Patients will also be given the option to partake in MYOPROSP for blood collection.
iv) UK neuromuscular biobank Blood/tissue related to the underlying disease process will be collected if being taken for clinical purposes. Blood samples will be used to extracted DNA, RNA, PBMC (peripheral blood mononuclear cells), serum and plasma samples which will also be stored for use in future studies. Additionally, patients will be asked for their permission to use their anonymised clinical and demographic details in any future research projects.
Blood sampling Patients consenting to take part in the study will be asked to provide blood samples as outlined above at baseline, 3 months, 6 months and 12 months. Normally, it is routine clinical practice to assess patients at these time points. These blood tests will be taken in addition to routine tests required during these assessments. Hence, although an additional blood sample will be taken, no additional venepuncture will be required thus minimising any inconvenience for the patient. In exceptional circumstances, it may be required that a blood sample is taken at an extra visit if clinic/nurse time is not available for this routine sampling. Standard laboratory assays or ELISA will be used for measuring serum enzyme, cytokine and antibody levels.
Patient questionnaires Clinical data will be attained regarding their level of disability (Stanford Health Assessment Questionnaire) and health outcome (EQ-5D-5L). When patients attend for review at each of the time points (3/6/12 months), they will be asked to complete these questionnaires. If the diagnosis is DM, patients will be asked to fill in the dermatology life quality index (DLQI) questionnaire, and if IBM, the Inclusion Body Myositis Functional Related Scale (IBM-FRS). The blood samples and questionnaires will already be labelled with a unique identifier and returned to the Centre for Musculoskeletal Research, The University of Manchester, using a pre-paid, pre-addressed blood box for the blood and a separate pre-paid stamped addressed envelope for the documentation.
The core dataset will comprise the UKMYONET basic dataset questionnaire and bloods for serum and plasma. Consent will also allow for further data collection as per the MYOPROSP study if the patient is under regular follow up. The International Myositis Assessment and Clinical Studies (IMACS) Group have agreed core-set measures to assess myositis disease activity, including assessment of the following:
IMACS core measures of disease activity
Muscle tissue is the primary organ affected in myositis, but other organs may also be involved, hence the requirement to capture extraskeletal disease activity using the Myositis Intention to Treat Index (MITAX) and the Myositis Activity Assessment by Visual Analogue Scales (MYOACT). The Myositis Damage Index (MDI) assesses extent and severity of damage. MITAX, MYOACT and MDI are all physician-initiated questionnaires. Further optional information can also be collected if performed as part of a routine clinical assessment, eg information on endurance.
Clinical Data As well as the information in the Core dataset, data will be captured at baseline including demographics, clinical disease classification, data detailing confirmation of diagnosis (including muscle biopsy, electromyography, autoantibody status, MR findings) co-morbidities and therapies. Changes in therapy will be captured at subsequent visits along with IMACS core measures. For IBM, additional monitoring will be performed including but not limited to IBM functional related scale, 6 minute walk test, timed up and go, grip strength.
MR imaging As a sub-study, patients will be given the option of having MR imaging of the femur to image the thigh musculature, and gadolinium-enhanced MR imaging of the heart at months 0 and 6. It is normal clinical practice to perform an MR of the femur at baseline and follow-up, and would be considered best practice to MR image the heart. In patients where gadolinium contrast would be deemed high-risk (renal impairment, history of previous contrast reactions), this would not be offered. A protocol will be developed in conjunction with musculoskeletal radiology colleagues to standardise the methods used for MR imaging in the different participating centres.
Muscle biopsy At diagnosis, a muscle biopsy is routinely performed under local anaesthetic in a non-invasive fashion. Several samples are usually taken in one pass, and one sample will stored in a PAXgene tube for RNA expression studies. The remainder of the samples will be processed and analysed in the local clinical histopathological departments. Muscle biopsy specimens will be snap-frozen in isopentane using liquid nitrogen and stored at -80C. Protocols for muscle tissue mounting, sectioning and storage that have already been tested and optimised as part of the UK juvenile dermatomyositis research study will be used. A further biopsy will be planned and offered at 6 months post-recruitment into the study. Although this is not routine clinical practice, an important clinical question needs to be addressed about the clinical utility of repeat biopsy and whether it may quantify change in disease activity and thus allow for accurate decision-making about treatment reduction/escalation.
|Study Type||Observational [Patient Registry]|
|Study Design||Observational Model: Cohort
Time Perspective: Prospective
|Target Follow-Up Duration||5 Years|
|Biospecimen||Retention: Samples With DNA
DNA RNA Peripheral blood mononuclear cells Serum Plasma Urine Muscle biopsies Other diagnostic tissue
|Sampling Method||Non-Probability Sample|
|Study Population||Idiopathic Inflammatory Myopathy, UK based patients|
|Study Groups/Cohorts||Idiopathic Inflammatory Myopathy
PM, DM, sIBM, necrotizing myopathy, anti-synthetase syndrome, suspected myopathy
|Publications *||Not Provided|
|Estimated Completion Date||February 2021|
|Estimated Primary Completion Date||February 2021 (Final data collection date for primary outcome measure)|
Gender Both female and males
Age limits Patients >/= 18 years
Accept healthy volunteers No
Study population description Patients referred to tertiary level UK myositis clinics
Sampling methods N/A, this is a prospective study of consecutive eligible patients
|Ages||Child, Adult, Senior|
|Accepts Healthy Volunteers||No|
|Listed Location Countries||United Kingdom|
|Removed Location Countries|
|Other Study ID Numbers||UoMMYO|
|Has Data Monitoring Committee||Yes|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||
|Responsible Party||Hector Chinoy, University of Manchester|
|Study Sponsor||University of Manchester|
|PRS Account||University of Manchester|
|Verification Date||January 2017|