Observational Prolonged Trial in Myotonic Dystrophy Type 1

Learn more about:
Related Clinical Trial
Effects of a 12-week Strength Training Program in Women With Myotonic Dystrophy Type 1 DMCRN-02-001: Assessing Pediatric Endpoints in DM1 Myotonic Dystrophy Type 1 and Resistance Exercise Phase 1/2 Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AOC 1001 Administered Intravenously to Adult Myotonic Dystrophy Type 1 (DM1) Patients Biomarker Development for Muscular Dystrophies Extracellular RNA Biomarkers of Myotonic Dystrophy Symptoms and Outcome Measures for Upper- Limb Function in Myotonic Dystrophy Type 1 Safety and Efficacy of Pitolisant on Excessive Daytime Sleepiness and Other Non-Muscular Symptoms in Patients With Myotonic Dystrophy Type 1 Poor Neck Proprioception May Cause Balance Deficits in Myotonic Dystrophy 1 Myotonic Dystrophy – Vascular and Cognition Effect of MYODM on Quality of Life, Fatigue and Hypersomnia in Patients With Myotonic Dystrophy Type 1 Open Label Study in Adolescents and Children With Myotonic Disorders European Home Mechanical Ventilation Registry Effects of SomatoKine (Iplex)Recombinant Human Insulin-like Growth Factor-1/Recombinant Human Insulin-like Growth Factor-binding Protein-3 (rhIGF-I/rhIGFBP-3) in Myotonic Dystrophy Type 1 (DM1) Safety and Efficacy Study of Recombinant Human Insulin-Like Growth Factor-I/Recombinant Human Insulin-Like Growth Factor Binding Protein-3 (rhIGF-I/rhIGFBP-3) In Myotonic Dystrophy Type 1 A Safety andTolerability Study of Multiple Doses of ISIS-DMPKRx in Adults With Myotonic Dystrophy Type 1 Sleep Breathing Disorders, a Main Trigger for Cardiac ARythmias in Type I Myotonic Dystrophy ? Safety, Tolerability and Pharmacokinetics of ERX-963 in Adults With Myotonic Dystrophy Type 1 Effects of a 12-week Strength Training Program in Men With Myotonic Dystrophy Type 1 Efficacy and Safety of DHEA for Myotonic Dystrophy Study of Tideglusib in Adolescent and Adult Patients With Myotonic Dystrophy Effects of a Multiple Component Training Program on Muscles in Adults With Myotonic Dystrophy Type 1 Ventilatory Response After Non Invasive Ventilation in Type 1 Myotonic Dystrophy Clinical Efficacy Trial of Mexiletine for Myotonic Dystrophy Type 1 DM-IMT – Controlled, Randomized, Three-arm Intervention Study on the Safety and Efficacy of Regular Respiratory Muscle Training in Patients With Myotonic Dystrophy Type 1 Venous Thromboembolism in DM1 Postural Spirometry Changes in Ambulatory Myotonic Dystrophy Patients Factors Associated With Hypoventilation in the Myotonic Dystrophy, Progressive Profile Over 5 Years PhenoDM1 (Myotonic Dystrophy Type 1 Natural History Study) Children’s Health Research Institute(CHRI), Stanford Lucile Packard Children Hospital (LPCH) Protocol on Myotonic Dystrophy Establishing Biomarkers and Clinical Endpoints in Myotonic Dystrophy Type 1 (END-DM1) Observational Prolonged Trial in Myotonic Dystrophy Type 1 Venous Thromboembolism in Myotonic Dystrophy Type 1 Myotonic Dystrophy Type 1 Aerobic Exercise Study Multicenter Observational Study of Myotonic Dystrophy Type 1 DM1 Heart Registry – DM1 Respiratory Registry

Brief Title

Observational Prolonged Trial in Myotonic Dystrophy Type 1

Official Title

Observational Prolonged Trial in Myotonic Dystrophy Type 1 to Improve Quality of Life Standards, a Target Identification Collaboration

Brief Summary

      Myotonic dystrophy type1 (DM1) is a rare, inherited, chronic progressive disease as well as
      an autosomal dominant multisystemic disorder. It is the most common adult form of muscular
      dystrophy, with a prevalence of approximately 10 per 100,000 people affected. With 733
      million people in Europe, we estimate that 75,000 people are DM1 patients in Europe.

      The aim of OPTIMISTIC is to improve clinical practice in the management of patients with this
      rare disease for which no dedicated treatment is currently available. OPTIMISTIC is a
      multi-centre, randomised controlled trial designed to compare a two component tailored
      behavioural change intervention to increase physical activity against standard patient
      management regimes, with particular attention given to the definition of appropriate outcome
      measures and new clinical guidelines for DM1 management. The two components of the
      intervention are 1) cognitive behavioural therapy (CBT) and 2) graded physical activity and
      we will evaluate the intervention's effectiveness and safety against standard patient
      management.

      Participants will be recruited from myotonic dystrophy clinics and neuromuscular centres in
      France, Germany, the Netherlands and the UK. A total of 286 male and female patients aged 18
      years and older with genetically proven classical or adult DM1 suffering from severe fatigue
      (only DM1 patients with a CIS subscale fatigue score > 35 are likely to benefit from the
      intervention), able to walk independently and able to complete the trial interventions will
      be included.

      A key objective of OPTIMISTIC is to provide outcome measures that are relevant for the
      patients and have a rate of change that is appropriate for a clinical trial timeframe. In
      addition, OPTIMISTIC will identify genetic factors that predict outcome and potential
      biomarkers as surrogate outcome measures that best explain the observed clinical variation.
    

Detailed Description

      Background DM1 is a rare, inherited, progressive disease as well as an autosomal dominant
      multisystemic disorder. It is the most common adult form of muscular dystrophy, with a
      prevalence of approximately 10 per 100,000 people affected. With 733 million people in
      Europe, we estimate that 75,000 people are DM1 patients in Europe. Typical symptoms of the
      disease include progressive muscle weakness and wasting from distal to proximal, ptosis,
      weakness of facial, jaw and anterior neck muscles, myotonia, daytime sleepiness, fatigue and
      cataract. Other symptoms of adult DM1 include cardiac conduction defects, as well as
      endocrine, gastrointestinal and cognitive dysfunction. DM1 is one of the most variable human
      diseases, has complex, multisystemic and progressively worsening clinical manifestations and
      leads to severe physical impairment, restricted social participation and premature death.

      There is no pharmaceutical treatment for causal or symptomatic relief of DM1 core symptoms
      (with the exception of Modafinil for excessive daytime sleepiness). Thus the aim of treatment
      is to relieve impairments, reduce limitations and optimise participation. Physical activity
      has been acknowledged as an important factor for health in general. For patients with a
      slowly progressive neuromuscular disease, such as DM1, there is accumulating evidence for
      prescribing low-to-moderate-intensity strength and aerobic exercise training, and an active
      lifestyle. Nevertheless, recent reviews conclude that existing studies are limited in number
      and quality, and that there is a need for disease-specific, randomised, controlled trials
      investigating the effect on quality of life.

      RATIONALE FOR THE STUDY It was demonstrated recently by an OPTIMISTIC research partner that
      severe fatigue, defined as a score equal to or higher than 35 on the subscale fatigue of the
      Checklist Individual Strength (CIS-fatigue), was reported by around 70% of patients with DM1.
      These severely fatigued patients had more problems with physical and social functioning as
      well as with their mental and general health than similar patients without severe fatigue.
      They also had more problems with concentration and planning. As such, experienced fatigue
      should be clearly distinguished from muscle weakness, which is probably the most common and
      characteristic symptom of DM1 and also of a lack of initiative (apathy) that is known to
      occur often in DM1.

      In a longitudinal study, we built a model of perpetuating factors for fatigue in patients
      with DM1. It appeared that lack of physical activity, sleep disturbances and pain all
      contributed to experienced fatigue. In addition, loss of muscle strength and pain contributed
      to fatigue through a lower level of physical activity. Ultimately, experienced fatigue and
      physical activity both contributed to the level of societal participation. A lack of
      initiative further increased fatigue but also had a direct negative effect on societal
      participation. Thus, theoretically, in order to improve societal participation one should
      compensate for a reduced initiative, optimise physical activity and alleviate experienced
      fatigue. To alleviate fatigue one should address the fatigue maintaining factors identified
      by the model, e.g. experience of pain or sleep disorders.

      The main rationale for the combination of CBT and physical activity is based on our
      DM1-specific model. The DM1-specific model shows that physical activity, experienced fatigue
      and lack of initiative are the main determinants of DM1 health status. OPTIMISTIC is the
      first model-based clinical trial in DM1. It evaluates the effect, and the maintenance of
      effects, of CBT combined with exercise training on the reduction of chronic fatigue in
      patients with DM1.

      Importantly, the intervention will also involve caregivers where they are willing to take
      part. The disabilities associated with DM1 put considerable strain on caregivers and can also
      lead to a negative interaction with the patient. The intervention will aim to support
      caregivers by installing realistic expectations about what can be expected from the patient,
      teach caregivers how to help patients to stay as self-reliant as possible and also reduce
      caregivers strain by taking time for themselves. If a DM1 patient has no caregiver or
      significant other, or no caregiver or significant other willing to take part in the study,
      the patient will not be excluded from the study. All patients will be asked if the study team
      could approach them to inform them for further research. This contact does not constitute
      consent.

      ** CMRI-substudy in People with DM1 People with DM1 are at high risk of developing a cardiac
      complication. However, it is not known whether the high prevalence of cardiac complications
      can be affected by a sedentary lifestyle. Given the high risk of cardiac complications and
      the possibility that becoming more physically active may help these complications, the
      University of Newcastle, will conduct a sub-study to perform Cardiac Magnetic Resonance
      Imaging (CMRI) in 40 eligible participants at baseline and at end of the intervention period
      to acquire the evidence upon which clinical judgement about the use of exercise as a clinical
      therapy that is safe, can be based.

      Cardiac Magnetic resonance imaging (CMRI) uses a combination of harmless radiofrequency (RF)
      waves and powerful magnets to cause hydrogen nuclei within the cardiac cell molecules to
      vibrate and emit RF energy. The MRI scanner detects the energy emissions and converts them to
      viewable images. When diseases begin, there are changes in the heart's tissue. Because even
      minor changes in tissue affect the rates at which energy is emitted, many medical conditions
      can be detected at their very early stages. MRI is done to evaluate the structure and
      function of the heart and blood vessels. MRI may provide information that cannot be obtained
      by other tests such as chest X-ray, ECG, echocardiogram, or nuclear tests.

      The CMRI examinations will be performed with the contract enhancement gadolinium, in 40
      eligible participants, 20 in each group. Participants will undergo:

        1. cardiac cine imaging, to evaluate cardiac morphology

        2. systolic and diastolic function and

        3. cardiac tagging to evaluate wall motion and torsion.

      MRI safety will be established prior to baseline and end of intervention scan. This includes;
      assessing for in vivo ferrous material, claustrophobia, abnormal renal function and
      pregnancy. The PI will assess renal function from the participant's medical notes at
      screening, if required a blood tests for U&Es will be requested. In addition, child-bearing
      potential female participants will consent to have urine pregnancy test performed.

      For participants that have had a baseline CMRI and withdraw from the study prior to the end
      of the intervention period, will be invited to have an end of study CMRI if the period from
      their initial CMRI is greater than 3 months.

      No further statistical review is required for the CMRI sub-study as only frequencies and
      associations will be assessed.
    


Study Type

Interventional


Primary Outcome

DM1-Activ

Secondary Outcome

 Six Minute Walk Test

Condition

Myotonic Dystrophy Type 1

Intervention

Behavioural change intervention

Study Arms / Comparison Groups

 Behavioural change intervention
Description:  Cognitive behavioural therapy (CBT) combined with exercise

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Behavioral

Estimated Enrollment

255

Start Date

April 2, 2014

Completion Date

October 17, 2016

Primary Completion Date

March 29, 2016

Eligibility Criteria

        Inclusion Criteria:

          -  Able to provide informed consent

          -  Genetically proven DM1

          -  Suffering from severe fatigue (CIS fatigue >35

          -  Able to walk independently

        Exclusion Criteria:

          -  Neurological or orthopaedic co-morbidity interfering with the interventions or
             possibly influencing outcomes.

          -  Use of psychotropic drugs (except Modafinil, Ritalin and antidepressants where the
             dosing regimen has been stable for at least 12 months prior to screening). If the
             doses of Modafinil or Ritalin increase during the 10 months of the intervention then
             the participant will be excluded.

          -  Severe depression as screening (judged as meeting DSM-IV criteria for a depressive
             episode).

          -  Participation in another clinical trial of an investigational medicinal product
             (CTIMP) or other interventional study considered to influence outcomes being evaluated
             in OPTIMISTIC.

          -  Unable to complete study questionnaires.

          -  Subject participating in another clinical trial (other than observational trials and
             registries) concurrently or within 30 days prior to screening for entry into this
             study.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Grainne Gorman, Dr, , 

Location Countries

France

Location Countries

France

Administrative Informations


NCT ID

NCT02118779

Organization ID

13/NE/0342

Secondary IDs

305697

Responsible Party

Principal Investigator

Study Sponsor

Radboud University Medical Center

Collaborators

 University of Newcastle Upon-Tyne

Study Sponsor

Grainne Gorman, Dr, Principal Investigator, Newcastle University


Verification Date

July 2017