PhenoDM1 (Myotonic Dystrophy Type 1 Natural History Study) (PhenoDM1)

• Sponsor: Newcastle-upon-Tyne Hospitals NHS Trust
• Information provided by (Responsible Party): Newcastle-upon-Tyne Hospitals NHS Trust

Study Description

Brief Summary:

PhenoDM1 will use patient reported outcomes to assess levels of pain, fatigue and quality of life in this cohort. Clinical and functional outcomes will look at muscle wasting and levels of myotonia. DNA, RNA, serum and CSF samples will be taken from all patients so that additional genetic and molecular biomarker analysis can be carried out. A subset of patients will undergo detailed sleep studies along with skeletal muscle MRI of the lower limbs. This study will complement the work of other groups currently looking at myotonic dystrophy type 1 using the same outcomes and measures where possible.

Condition or disease
Myotonic Dystrophy Type 1

Detailed Description:

Myotonic Dystrophy type I (DM1) is the most common form of adult muscular dystrophy, affecting 1 in 8000 individuals. It is an autosomal dominant disorder with multisystemic involvement of multiple organs and tissues, namely brain, heart, endocrine system, eyes and both smooth and skeletal muscles. It results from the CTG expansion of an untranslated region 3' terminal of the DMPK gene which causes a disturbance of the RNA metabolism, in particular defective splicing of various pre-mRNAs such as the muscular chloride channel (causing myotonia), the insulin receptor (causing diabetes) and others. We will carry out an in-depth characterisation of 400 adult DM1 patients identified from local clinical populations across England and through the national DM Registry. Over a two year period we will take measurements 12 months apart to address specific symptoms that cause major quality of life impairment including muscle weakness, myotonia, excessive daytime sleepiness and cognitive impairment. DNA samples will be collected in order to determine the CTG repeat length and serum samples for biomarker identification. We will carry out muscle MRI and sleep studies in a subset of 50 patients. The implemented measures will capitalise on the efforts of previous cohort studies ensuring that all measures are comparable with existing datasets.

Study Design

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Study Type :	Observational
Actual Enrollment :	213 participants
Observational Model:	Cohort
Time Perspective:	Prospective
Official Title:	Myotonic Dystrophy Type 1 (DM1) Deep Phenotyping to Improve Delivery of Personalized Medicine and Assist in the Planning, Design and Recruitment of Clinical Trials
Actual Study Start Date :	August 2015
Estimated Primary Completion Date :	October 31, 2018
Estimated Study Completion Date :	October 31, 2018

Groups and Cohorts

Group/Cohort
Myotonic Dystrophy type 1 (DM1) patients; Natural History Study

Outcome Measures

Primary Outcome Measures :

1. Strength and function [ Time Frame: 9-12 months ]

   These assessments include:

   • Manual Muscle Testing
   • Quantitative Muscle Testing (Hand Held Myometry, Hand-Grip Dynamometry)
   • Pulmonary function testing (FVC and MIP)
   • Functional evaluations (Nine Hole Peg Test, Six Minute Walk Test, 30 Seconds Sit and Stand Test, Timed 10-Meter Walk Test, Scale for Assessment and Rating of Ataxia Scale, Accelerometry Assessment)

Secondary Outcome Measures :

1. Cognitive assessment [ Time Frame: 9-12 months ]

   These questionnaires include:

   • Mini-Mental State Examination (MMS)
   • Trail Making Test (TMT)
   • Apathy Evaluation Scale (AES)
2. Quality of Life using patient-reported outcomes [ Time Frame: 9-12 months ]

   These questionnaires include:

   • Individualised Neuromuscular Quality Of Life (InQoL)
   • Myotonic Dystrophy Health Index (MDHI)
3. Fatigue and Daytime Sleepiness assessment using patient-reported outcomes [ Time Frame: 9-12 months ]

   These questionnaires include:

   • Checklist Individual Strength
   • Epworth Sleepiness Scale
   • Fatigue and Daytime Sleepiness Scale
4. Pain assessment using patient-reported outcomes [ Time Frame: 9-12 months ]

   These questionnaires include:

   • McGill questionnaire
   • IVR Scale
5. Blood and Urine collection for genetic and molecular biomarker analysis [ Time Frame: 9-12 months ]
   Collection of: RNA, DNA, Serum and Urine
6. Blood collection for Glycated Haemoglobin (HbA1c), Thyroid hormones, Androgens (in males only) analysis [ Time Frame: 9-12 months ]

Other Outcome Measures:

1. Sleep Study [ Time Frame: 9-12 months ]
   Assessment by polysomnography and maintenance of wakefulness test (MWT)
2. Skeletal Muscle MRI of the lower extremities [ Time Frame: 9-12 months ]
   Three imaging scans will be acquired of the lower extremities: T1-weighted images, TIRM images and Dixon images.

Biospecimen Retention:   Samples With DNA

All blood and urine will be processed and stored in Newcastle Biobank for Research of Neuromuscular Disorders (Newcastle and North Tyneside 1 -REF/08/H0906/28).

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No
Sampling Method:	Probability Sample

Study Population

Inclusion criteria will be limited to those over 18 years of age, with a genetic confirmation of DM1 who are able to provide informed consent. This unrestrictive approach will enable assessment of a true cross-section of the population, including those with congenital, childhood and adult onset. Two substudies will be open to a subset of patients, one assessing muscle through MRI and on focussing on sleep and fatigue. Additional restrictions may be in place to ensure the safety of the participants during these studies.

Informed consent will be obtained from all patients, including detailed patient information. Sharing and storage of data and samples will be discussed in this information and covered appropriately in the consent.

Criteria

Inclusion Criteria:

Main Inclusion Criteria

1. 18 years of age or over
2. Genetic confirmation of Myotonic Dystrophy Type 1
3. Able to consent and willing to participate throughout the duration of the study.

Additional Inclusion Criteria for MRI study:

1. Aged between 18 and 55 years
2. Ambulant or ambulant-assisted

Additional Inclusion Criteria for sleep study:

1. Aged between 18 and 55 years

Exclusion Criteria:

Main Exclusion Criteria

1. Inability to give informed consent
2. If the clinician presumes that the patient will not be able to perform any of the motor function tests involved (Six Minute Walk Test, 30 Seconds Sit and Stand Test, Timed 10-Meter Walk Test)
3. Inability to perform the cardiac and pulmonary assessments

Additional Exclusion Criteria for MRI study:

1. Pacemaker, ICD or non-MRI-compatible prosthetic material.

Additional Exclusion Criteria for sleep study:

1. ventilated patients
2. patients medicated with stimulants, including Modafinil
3. patients medicated with benzodiazepines or antidepressants

Contacts and Locations

Locations

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United Kingdom
Newcastle-upon-Tyne Hospitals NHS Trust
Newcastle Upon Tyne, Tyne And Wear, United Kingdom, NE1 4LP
University College London Hospitals NHS Foundation Trust, National Hospital for Neurology and Neurosurgery
London, United Kingdom, WC1N 3BG

Sponsors and Collaborators

Newcastle-upon-Tyne Hospitals NHS Trust

Investigators

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Principal Investigator:	Hanns Lochmuller, MD, FAAN	University of Newcastle Upon-Tyne
Principal Investigator:	Chris Turner, FRCP, PhD	National Hospital for Neurology and Neurosurgery

More Information

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Responsible Party:	Newcastle-upon-Tyne Hospitals NHS Trust
ClinicalTrials.gov Identifier:	NCT02831504 History of Changes
Other Study ID Numbers:	7491
First Posted:	July 13, 2016
Last Update Posted:	March 29, 2018
Last Verified:	March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Yes

Keywords provided by Newcastle-upon-Tyne Hospitals NHS Trust:

Myotonic Dystrophy type 1; DM1; Muscular Dystrophy; Neuromuscular Diseases

Additional relevant MeSH terms:

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Myotonic Dystrophy; Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Myotonic Disorders	Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn