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Brain Involvement in Myotonic Dystrophy Type I: From Functional Neuroimaging to the Impact on Quality of Life (BrainDM)

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. Read our disclaimer for details. Identifier: NCT03589677
Recruitment Status : Completed
First Posted : July 18, 2018
Last Update Posted : July 18, 2018
Information provided by (Responsible Party):
prof. Corrado Angelini, IRCCS San Camillo, Venezia, Italy

Brief Summary:
This project aims to characterize DM1 patients, by collecting clinical, neuropsychological, neuroimaging, and molecular rehabilitative data, in order to elucidate the etiology of cognitive troubles, with special attention to the impact of those dysfunctions on quality of life.

Condition or disease
Myotonic Dystrophy Type 1 (DM1)

Detailed Description:
Myotonic Dystrophy Type 1 (DM1), the most common form of muscular dystrophy in adulthood, is characterized by a multisystemic involvement in skeletal muscle (atrophy and progressive hyposthenia, predominantly in the distal districts, and myotonic phenomenon), and of the cardiac, ocular, endocrine, gastrointestinal and central nervous system (CNS) systems. The disease, of a genetic nature, is transmitted as an autosomal dominant trait and is due to an abnormal expansion of the CTG nucleotide triplet of the gene that encodes a kinase protein (DMPK), located on chromosome 19q13.3. Based on the expansion number of nucleotide triplets, 4 classes of expansion were identified: E1, E2, E3, E4, which are directly related to the severity of the phenotype. The pathogenetic basis of the disease is not yet clear to date; however, it is hypothesized that the mutation results in the expression of abnormal RNA transcripts that induce an alteration of the splicing mechanisms of different gene products. The disease frequently presents a typical profile of CNS disorders, characterized by a chronic and progressive pattern. The clinically identifiable symptomatology consists of cognitive disorders (visual-spatial, attention, executive functions), from alterations in the emotional sphere (depressed mood, anxiety and apathetic temperament) and from obsessive / avoiding / passive-aggressive personality traits. A difficulty in recognizing facial emotional states has also been reported. The overall intellectual performance tends to be at the lower limits of the norm when compared to the population of equal age and education. From the neuroradiological point of view, the presence of cortical atrophy, usually more evident in the frontal and temporal, and of white matter lesions spread on both hemispheres, often asymmetric, was detected. Despite the high number of studies on the subject, the frequency and localization of these abnormalities, as well as their relationship to cognitive involvement, the age of onset, duration of disease and genetic profile have not yet been clarified. In clinical practice, patients frequently present a partial impairment of insight, or the psychological ability to have a clear and complete awareness of their condition of illness, the incidence of which, however, has never been investigated. This disorder, also defined by the name of anosognosia, generates in the patient a partial admission of difficulties, which interferes with its adaptability to treatments and in the relationship with the caregiving figures. Lack of awareness about one's state of illness is a psychological condition found in various neurological diseases of an organic or neurodegenerative nature. The neuroanatomical and neuropsychological bases are complex and to date not fully known. The frontal lobes have been identified as possible neuroanatomical localizations of the disorder; however, data in the literature about the relationship between executive function deficits and anosognosia are extremely conflicting. In this patients, the rehabilitative intervention is useful for optimizing muscle tropism and prevents further atrophy of disused muscle fibers. MicroRNAs (miRNAs/miRs) miR-1, miR-206, miR-133a, and miR-133b are called "myomiRs" and are involved in myogenesis, muscle maintenance, and recovery and can be used as possible biomarkers to follow the effectiveness of rehabilitation treatment. There are currently no similar studies on patients with DM1.

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Study Type : Observational
Actual Enrollment : 50 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Brain Involvement in Myotonic Dystrophy Type I: From Functional Neuroimaging to the Impact on Quality of Life
Actual Study Start Date : July 3, 2012
Actual Primary Completion Date : June 4, 2015
Actual Study Completion Date : June 4, 2015

Myotonic dystrophy type 1

Subjects of both sexes with a diagnosis of Steinert's disease (DM1), de novo or with the previous diagnosis that shows significant worsening detectable during the follow-up foreseen by the normal cure procedure with clinical presentation indicating a CNS compromise will be evaluated for:

  • quality of life evaluation
  • exam of neuroimaging
  • study of myomiRNAs before and after rehabilitation

Primary Outcome Measures :
  1. Study of quality of life with INQoL test in DM1 patients [ Time Frame: Study of quality of life in DM1 patients. Estimated duration: about 15 months ]
    The Individualized Neuromuscular Quality of Life Questionnaire (INQoL) patients and caregivers' score will be used for define the possible impact of the pathology on the patient's quality of life. Will be used the INQoL Italian version validated in 2010 (Sansone et al. 2010)

Secondary Outcome Measures :
  1. Brain MRI neuroimaging in DM1 patients [ Time Frame: Estimated duration: about 16 months. ]
    Brain DM1 neuroimaging examination with MRI T1 sequences will be collected using 1.5 Tesla scanner and analyzed to verified the possible presence of structural brain alteration. T1 sequences will be used to evaluate cortical atrophy in DM1 patients.

  2. Study of circulating myomiRNAs in DM1 patients before and after rehabilitation [ Time Frame: Estimated duration: about 16 months. ]
    New circulating molecular biomarkers, muscle specific-microRNAs (myomiRNAs), will be studied, before and after a period of 6 weeks of rehabilitation protocol, in blood of DM1 patients. MyomiRNAs could be used to evaluate the effect of physical rehabilitation since they appear to be linked to muscle atrophy. Rehabilitation protocol and methodologies have been published and validated by Cudia (Cudia et al.; 2016)

Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
DM1 subjects of both sexes: de novo or with previous diagnosis that show significant worsening detectable during the follow-up foreseen by the normal cure procedure with clinical presentation indicating a CNS compromise. DM1 is frequently characterized by a significant involvement of the CNS, causing cognitive disorders, mood and behavior, varying from case to case.

Inclusion Criteria:

  • Age between 20 and 60 years;
  • Presence of cognitive disorders declared by the patient or family members spontaneously or at the specific request of the physician, not to compromise the ability to understand and adhere to what is required by the study protocol;
  • Suspected leukoencephalopathy;
  • Signing of written informed consent.

Exclusion Criteria:

  • clinical picture mainly referring to other neurological diseases (eg dementia, stroke outcomes, etc ...)
  • incompatibility with the eligibility criteria: subjects with DM1 who do not show symptoms of involvement of the central nervous system; subjects with previous diagnosis.
  • impossibility to perform magnetic resonance examinations as they are dangerous for the patient's health;
  • patients with severe psychiatric disorders: Axis 1 or 2 of Diagnostic and Statistical Manual of Mental Disorders (DSM IV);
  • patients with severe or severe mental retardation: Intelligence Quotient (IQ) at the Wechsler Adult Intelligence Scale (WAIS) <of 45.
  • Abuse of alcohol or other psychoactive substances.


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Responsible Party: prof. Corrado Angelini, professor, M.D., IRCCS San Camillo, Venezia, Italy Identifier: NCT03589677    
Other Study ID Numbers: IRCCSSanCamillo
First Posted: July 18, 2018    Key Record Dates
Last Update Posted: July 18, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by prof. Corrado Angelini, IRCCS San Camillo, Venezia, Italy:
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