Myotonic Dystrophy Type 1 Congenital and Juvenile Form: From Diagnosis to Rehabilitation [MDCJ-NeuBeRe] (MDCJ-NeuBeRe)

Myotonic Dystrophy Type 1 Congenital and Juvenile Form: From Diagnosis to Rehabilitation

The rationale of the study is to collect structured data in the neuropsychological, clinical neuroradiologic and neurorehabilitation fields in children/young people affected by congenital and juvenile myotonic dystrophy. Children affected by the congenital form (CDM1) present important brain alterations present since birth while, on the contrary, patients with the adult form of DM1 often present a degenerative, slowly progressive neurocognitive picture. Promising therapies that aim to correct the molecular mechanism underlying the symptoms of adult forms of DM1 are under development, but their potential role at the level of the nervous system and in particular in forms of CDM1 (which appears to be a distinct disorder of neuronal development) is also to be clarified.

To this end, a better definition of neurocognitive profiles and their evolution is essential for the purposes of evaluating the effectiveness of experimental therapies.

Study Overview

• Status: Recruiting
• Conditions: Myotonic Dystrophy 1
• Intervention / Treatment: Diagnostic test: neurocognitive evaluations

Detailed Description

A. Recruitment of patients with a defined diagnosis of Myotonic Dystrophy type 1 (see following inclusion and exclusion criteria)

B) Clinical and cognitive evaluation

1. neurological and neuromuscular examination, compilation of the MIRS-muscle scale and EPWORTH scale-daytime sleepiness (1 session of approximately 1 hour);

2. administration of a neuropsychological battery, in order to define the level of cognitive functioning and to frame a detailed function-specific profile (multiple sessions to be defined based on the collaboration of the patients) investigating the following areas:

   1. intelligence quotient;
   2. attention;
   3. memory;
   4. visual-constructive skills and executive functions
3. psychiatric examination and administration of psychological tests (MMPI-2, Minnesota Multiphasic Personality Inventory 2) to investigate any psychopathologies (behavioral disorders, anxiety disorders, developmental disorders, hyperactivity/attention deficit) and to define the psychological-behavioral profile and adaptive (Vineland Adaptive Behavioral Scale)
4. neuroimaging examination through Morphological magnetic resonance and Diffusor Tensor imaging and Voxel Based Morphometry protocols
5. based on the clinical conditions, a cardiological evaluation will also be carried out (including instrumental tests such as Electrocardiogram ECG, echocardiogram and 24-hour ECG) and pneumological evaluation (with recording of nocturnal oximetry, spirometry), eye examination, phoniatric examination and logopedic evaluation (aimed at evaluating chewing/swallowing)

• Study Type: Observational
• Enrollment (Estimated): 30

Contacts and Locations

• Study Contact: Name: Maria G D'Angelo, MD; Phone Number: +39 031877870; Email: grazia.dangelo@lanostrafamiglia.it

Study Locations

• Italy
  • Lecco
    • Bosisio Parini, Lecco, Italy, 23842
      • Recruiting
      • Maria Grazia D'Angelo
      • Contact: Maria Grazia D'Angelo; Phone Number: +39031 877870; Email: grazia.dangelo@lanostrafamiglia.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with a defined diagnosis of MYotonic Dystrophy type 1, congenital and juvenile form

Description

Inclusion criteria:

1. genetically defined diagnosis of Steinert myotonic dystrophy
2. age <35 years
3. reading and signing the informed consent. For the congenital form: presence of hypotonia and weakness at birth, for the juvenile form: onset between 1 and 10 years with normal pre-perinatal history.

Exclusion criteria

1. other concomitant pathologies that completely prevent the execution of clinical assessments
2. presence of devices and prostheses that prevent the execution of the MRI
3. lack of family compliance. -

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Myotonic Dystrophy type 1; Myotonic Dystrophy type 1 -congenital form Myotonic Dystrophy type 1-infantile form	Diagnostic test: neurocognitive evaluations; clinical and neurocognitive evaluations neuroradiological evaluation through cerebral magnetic resonance; Other Names: cerebral imaging

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Motor function evaluation by Muscular Impairment Rating Scale	Muscular Impairment Rating Scale (MIRS) in assessing patients with myotonic dystrophy type 1 (DM1). The MIRS is a ordinal five-point rating scale, where grade 1 = no clinical muscular impairment; grade 2 = early muscular impairment (clinical myotonia, facial weakness, and weakness of neck flexors) without limb weakness; grade 3 = distal weakness; grade 4 = mild to moderate (3 ≤ core < 5) proximal weakness; grade 5 = severe (MRC score<3)proximal weakness proximal weakness	through study completion,an average of 2 years
cognitive evaluation by Wechsler Intelligence scale	Wechsler Intelligence scale: mean score 100 SD 15 (SD: Standard Deviation):deficiency when 2 Standard Deviation below average)	through study completion,an average of 2 years
cognitive evaluation by Raven Matrices	Raven Matrices , Z scores=/> 0,00 (in range); Z scores =/< -2,00 (deficiency)	through study completion,an average of 2 years
cognitive evaluation by Continous Performance Test 3	Continous Performance Test 3: T mean Scores 50 SD 10 (SD: standard deviation) (T=45-59 in range; T =/>60 below range)	through study completion,an average of 2 years
cognitive evaluation by Trail Making Test A-B	Trail Making Test A-B: Z scores=/> 0,00 (in range); Z scores =/< -2,00 (deficiency)	through study completion,an average of 2 years
cognitive evaluation by Digit Span and CORSI Test	Digit Span and CORSI Test:Z scores=/> 0,00 (in range); Z scores =/< -2,00 (deficiency)	through study completion,an average of 2 years
cognitive evaluation by Rey Figure test	Rey Figure test: Z scores=/> 0,00 (in range); Z scores =/< -2,00 (deficiency):	through study completion,an average of 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
clinical evaluation by Epworth Sleepiness Scale	Epworth Sleepiness Scale: scores from 0 to 24; above 10, clinical risk.	through study completion,an average of 2 years
cognitive evaluation by Wisconsin Card Sorting Test	Wisconsin Card Sorting Test: mean score 100 SD 15 (SD: standard deviation) : deficiency when 2 Standard Deviation below average	through study completion,an average of 2 years
cognitive evaluation by Tower of London test	Tower of London:mean score 100 SD 15 deficiency when 2 Standard Deviation below average)	through study completion,an average of 2 years
cognitive and behavioral evaluation by Minnesota Multiphasic Personality Inventory	Minnesota Multiphasic Personality Inventory- MMPI 2: mean score 50 SD 10 ((SD: standard deviation)	through study completion,an average of 2 years
cognitive and behavioral evaluation by Vineland Adaptive Behavior Scales	Vineland Adaptive Behavior Scales mean score 100 SD 15 (SD: standard deviation) :deficiency when 2 Standard Deviation below average	through study completion :an average of 2 years

Collaborators and Investigators

• Sponsor: IRCCS Eugenio Medea

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2022
• Primary Completion (Actual): March 18, 2024
• Study Completion (Estimated): December 30, 2024

Study Registration Dates

• First Submitted: March 19, 2024
• First Submitted That Met QC Criteria: April 19, 2024
• First Posted (Actual): April 22, 2024

Study Record Updates

• Last Update Posted (Actual): April 22, 2024
• Last Update Submitted That Met QC Criteria: April 19, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: neuropsychological evaluation; Myotonic dystrophy congenital form; Myotonic dystrophy infantile form; behavioral evaluation; brain imaging study
• 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: MEDEA 975

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No