Clinical trial NCT03589677: Brain Involvement in Myotonic Dystrophy Type I: From Functional Neuroimaging to the Impact on Quality of Life
Official title: Brain Involvement in Myotonic Dystrophy Type I: From Functional Neuroimaging to the Impact on Quality of Life
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Myotonic Dystrophy Type 1 (DM1)
Keywords: DM1
Brain
MRI
Lead sponsor: IRCCS San Camillo, Venezia, Italy
Sponsor class: OTHER
First posted: 2018-07-18
Enrollment: 50
Sex: ALL
Minimum age (years): 20
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Study of quality of life with INQoL test in DM1 patients
timeFrame: Study of quality of life in DM1 patients. Estimated duration: about 15 months
Secondary outcomes:
measure: Brain MRI neuroimaging in DM1 patients
timeFrame: Estimated duration: about 16 months.
measure: Study of circulating myomiRNAs in DM1 patients before and after rehabilitation
timeFrame: Estimated duration: about 16 months.
Other outcomes:
Locations:
Study officials:
References:
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