Low-frequency Repetitive Nerve Stimulation in Myotonic Dystrophy Type 1

NCT05662150 | Completed DMC

• 1 other identifier: Steinert study
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

The study design is a prospective cohort study. It aims to evaluate the neuromuscular junction in dystrophic myotonia 1 (DM 1) using low-frequency repetitive nerve stimulation (RNS) on several nerve-muscle pairs of the one side including proximal and distal muscles of upper and lower extremities. First, it will be investigated whether a decrement with 3 Hz stimulation, as described in literature, is reproducible in our patient population. If this is the case, it will be examined whether it is the consequence of a dysfunction of the neuromuscular junction or rather linked to a hypo-excitability of some muscle fibers due to myotonia. For this purpose, additional tests including short exercise test (to observe any decrement resulting from an inexcitability in myotonic muscle fibers) and needle EMG (for mapping myotonic discharges in the muscles tested with repetitive nerve stimulation) will be performed. Single fiber-EMG will not be provided in this study as an abnormal result does not necessarily indicate a dysfunction of the neuromuscular junction but could just as well be due to the muscular dystrophy in the context of DM1. Finally, it will be investigated if there is a correlation between the decrement with 3 Hz stimulation and clinical signs as fixed muscle weakness (via Medical Research Counsil (MRC) scale, DM-activ scale \[30\]) and fatigue (via MG-ADL scale).

Conditions

Myotonic Dystrophy 1

Outcome Measures

Primary Outcomes (1)

• Reproducibility of rapid decrement at low frequency stimulation.

  Low stimulation frequency was tested in 6 muscles, to verify the presence of an anomalie of the neuromuscular transmission.

  1 year

Secondary Outcomes (2)

• Correlation of decrement with grade of EMG-myotonia

  1 year

• Is there any clinical expression (muscle fatigability) of a possible neuromuscular junction dysfunction

  1 year

Study Arms (4)

Questionnaires

ACTIVE COMPARATOR

Patients with DM1 were asked to complete a questionnaire to rate a 25-item activity scale (DM1-Activ) and the Myasthenia Gravis Activity of Daily Life scale (MG-ADL) to rate their level of functional burden. For the DM1-Activ a score of 40 alludes no impairment and a score of 0 indicates the highest functional burden of physical activity. This scale has proven to be practical, reliable and valid. For the MG-ADL the total score ranges from 0 to 24, a score of 0 denotes no and 24 the highest functional burden. It should be noted that this scale is not adjusted for DM1. The rationale was to gain information about muscle fatigue and consequently the neuromuscular junction.

Diagnostic Test: Low frequency repetitive stimulation

grip strength via dynamometer

ACTIVE COMPARATOR

The isometric grip strength was tested by using a dynamometer. The subject will be asked to perform an increasing force against the dynamometer over a period of several seconds.

Diagnostic Test: Low frequency repetitive stimulation

short exercise test

ACTIVE COMPARATOR

The subject was asked to contract the ADM muscle as hard as possible in isometric conditions for 10 seconds. CMAP's was recorded 2 seconds after the end of the exercise and then every 10 seconds for 50 seconds.

Diagnostic Test: Low frequency repetitive stimulation

needle EMG

ACTIVE COMPARATOR

The electrical myotonia of each examined muscle was scored according to the Streiss and Sun scale.

Diagnostic Test: Low frequency repetitive stimulation

Interventions

Low frequency repetitive stimulation DIAGNOSTIC_TEST

Neuromuscular transmission was tested by using short-lasting low frequency RNS (10 stimuli at 3 Hz). The test was applied on the abductor digiti minimi (ADM), anterior tibial, orbiculis oculi, trapezius, anconeus and EDB muscles of one side, in this particular order, by supramaximal stimulation of the corresponding nerve.

Questionnaires; grip strength via dynamometer; needle EMG; short exercise test

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• \* genetically confirmed DM1

You may not qualify if:

• minor age
• auto-immune diseases
• medical conditions involving the neuromuscular junction: (myasthenia gravis, Lambert-Eaton myasthenic syndrome, congenital myasthenia syndromes).

Sponsors & Collaborators

• Vrije Universiteit Brussel: lead

Study Sites (1)

UZ Brussel

Jette, Brussels Capital, 1000, Belgium

Location

MeSH Terms

Conditions

Myotonic Dystrophy

Condition Hierarchy (Ancestors)

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; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Jella De Ville, MD

  Universitair Ziekenhuis Brussel

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: medical doctor, principal investigator

Study Record Dates

• First Submitted: October 14, 2022
• First Posted: December 22, 2022
• Study Start: September 1, 2021
• Primary Completion: June 11, 2022
• Study Completion: June 20, 2022
• Last Updated: December 22, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)