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

Myotonic Dystrophy Type 1 (DM1) Deep Phenotyping to Improve Delivery of Personalized Medicine and Assist in the Planning, Design and Recruitment of Clinical Trials

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.

Study Overview

• Status: Completed
• Conditions: 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 Type: Observational
• Enrollment (Actual): 213

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Strength and function	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)	9-12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive assessment	These questionnaires include: Mini-Mental State Examination (MMS); Trail Making Test (TMT); Apathy Evaluation Scale (AES)	9-12 months
Quality of Life using patient-reported outcomes	These questionnaires include: Individualised Neuromuscular Quality Of Life (InQoL); Myotonic Dystrophy Health Index (MDHI)	9-12 months
Fatigue and Daytime Sleepiness assessment using patient-reported outcomes	These questionnaires include: Checklist Individual Strength; Epworth Sleepiness Scale; Fatigue and Daytime Sleepiness Scale	9-12 months
Pain assessment using patient-reported outcomes	These questionnaires include: McGill questionnaire; IVR Scale	9-12 months
Blood and Urine collection for genetic and molecular biomarker analysis	Collection of: RNA, DNA, Serum and Urine	9-12 months
Blood collection for Glycated Haemoglobin (HbA1c), Thyroid hormones, Androgens (in males only) analysis		9-12 months

Other Outcome Measures

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

Collaborators and Investigators

• Sponsor: Newcastle-upon-Tyne Hospitals NHS Trust
• Investigators: Principal Investigator: Hanns Lochmuller, MD, FAAN, University of Newcastle Upon-Tyne; Principal Investigator: Chris Turner, FRCP, PhD, National Hospital For Neurology and Neurosurgery

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2015
• Primary Completion (Actual): October 31, 2018
• Study Completion (Actual): October 31, 2018

Study Registration Dates

• First Submitted: March 22, 2016
• First Submitted That Met QC Criteria: July 8, 2016
• First Posted (Estimate): July 13, 2016

Study Record Updates

• Last Update Posted (Actual): April 13, 2021
• Last Update Submitted That Met QC Criteria: April 12, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Neuromuscular Diseases; DM1; Muscular Dystrophy; Myotonic Dystrophy type 1
• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Muscular Disorders, Atrophic; Heredodegenerative Disorders, Nervous System; Muscular Dystrophies; Myotonic Disorders; Myotonic Dystrophy
• Other Study ID Numbers: 7491

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes