Ultrasonographic Muscle Assessment and Functional Scales in Spinal Muscular Atrophy

Active, not recruiting

• Conditions: Spinal Muscular Atrophy (SMA); Neuromuscular Disease
• Interventions: Diagnostic Test: Ultrasonographic Assessment

• Registration Number: NCT06599606
• Lead Sponsor: Istanbul University - Cerrahpasa (IUC)

Brief Summary

This study aims to investigate the relationship between ultrasonographic muscle thickness measurement and echogenicity assessment with functional scales in children with spinal muscular atrophy (SMA). By utilizing ultrasonographic techniques, the study seeks to provide objective biomarkers for assessing muscle health and monitoring treatment response. Currently, the evaluation of SMA often relies on subjective clinical assessments; this study addresses that gap by offering more precise and objective indicators of disease progression and functional status. The ultimate goal is to improve treatment strategies and enhance patient outcomes through better assessment tools.

Detailed Description

Spinal muscular atrophy (SMA) is a neuromuscular disorder that typically leads to progressive lower motor neuron loss from early childhood. The most common form is caused by deletions in the survival motor neuron 1 (SMN1) gene, inherited in an autosomal recessive manner. SMA is classified into at least three subtypes based on the age of onset and the level of motor development achieved. In Type 1 SMA (severe form), symptoms usually appear before 6 months of age, and children are unable to sit unsupported. In Type 2 SMA (intermediate form), symptoms start between 6 and 18 months, and children cannot walk unsupported. Type 3 SMA (mild form) presents after the second year of life, and affected children can walk unsupported. Although the exact prevalence and carrier rates of SMA in our country are not fully determined, it is estimated that there are between 130 and 180 new cases annually, given approximately 1,200,000 live births each year. The total number of SMA patients in the country is about 3,000.

Despite current treatments, muscle weakness and significant functional loss affecting quality of life are commonly observed in SMA patients. At present, the efficacy of SMA treatment is measured through clinical assessment, including monitoring of changes in motor developmental milestones and functional scales. However, the lack of objective biomarkers that are less reliant on patient cooperation, as opposed to functional scales, complicates monitoring treatment response for patients. Establishing reliable methods to assess disease progression and treatment response is crucial for conducting robust clinical studies.

Musculoskeletal ultrasonography presents itself as a suitable imaging modality for use as a biomarker in SMA management due to its non-invasiveness, repeatability, absence of radiation, ability to evaluate multiple muscles quickly, and ease of application. Furthermore, the feasibility of performing ultrasonographic examinations at the bedside facilitates access to a larger number of patients, especially those with limited mobility or requiring respiratory support. Previous literature has reported the advantages of muscle ultrasonography in evaluating neuromuscular disorders, including SMA.

In conclusion, this study, which will investigate the relationship between ultrasonographic muscle thickness measurement and echogenicity evaluation and functional scales in patients diagnosed with SMA for the first time in our country, will guide physicians and researchers seeking to assess disease progression, determine treatment efficacy, and develop rehabilitation strategies.

Study Timeline

• Study Start: 2024-05-01
• Status Verified: 2024-09
• Study First Submitted: 2024-09-12
• Study First Submitted QC: 2024-09-12
• Last Update Submitted: 2024-09-12
• Study First Posted: 2024-09-19
• Last Update Posted: 2024-09-19
• Primary Completion: 2025-02-01
• Study Completion: 2025-05-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 34

Inclusion Criteria

• Age between 0-18 years
• Confirmed diagnosis of SMA through genetic testing
• Having received four loading doses of nusinersen
• Written consent provided for participation in the study

Exclusion Criteria

• History of surgical operation or trauma in the muscles to be examined
• Presence of spasticity that complicates positioning of the extremities and hinders ultrasound imaging

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Case	Ultrasonographic Assessment	Patients diagnosed with spinal muscular atrophy (SMA) who have received at least four loading doses of nusinersen
Control	Ultrasonographic Assessment	Healthy, age- and sex-matched control individuals

Primary Outcome Measures

Name	Time	Method
Muscle Thickness Measurement	Baseline	Muscle thickness in specific muscle groups will be assessed using ultrasonography. Measurements will include biceps brachii/brachialis, quadriceps, forearm flexors, and tibialis anterior. Thickness will be measured at predetermined anatomical sites using electronic calipers.
Muscle Echogenicity Assessment	Baseline	Muscle echogenicity will be assessed by calculating luminance ratios (LR) from ultrasonographic images. Luminance ratios will be calculated for the target muscle groups (biceps brachii/brachialis, quadriceps, forearm flexors, tibialis anterior, triceps, proximal hamstrings, gastrosoleus) and compared to subcutaneous tissue. This will involve measuring and analyzing images using ImageJ software.

Secondary Outcome Measures

Name	Time	Method
CHOP-INTEND	Baseline	CHOP-INTEND (Childrens Hospital of Philadelphia Infant Test of Neuromuscular Disorders) is a clinical scale designed to assess the motor function of infants with type 1 SMA or other types of SMA who cannot sit unsupported. This scale comprises 16 items that focus on evaluating the infant's movements, posture, and reflexes.
HFMSE	Baseline	HFMSE (Hammersmith Functional Motor Scale-Expanded) is a scale used to assess motor skills in patients with type 2 and type 3 SMA who can sit unsupported. It consists of 33 items that score various movements, including sitting, rolling in a prone position, lifting the head in a prone position, rising, kneeling, standing, walking, jumping, and climbing stairs.
RULM	Baseline	RULM (Revised Upper Limb Module) is a scale designed to assess functional abilities in the upper extremities of SMA patients. The scale includes an entry item to determine functional levels and consists of 19 items covering both distal and proximal movements.

Trial Locations

Locations (1)

Istanbul University - Cerrahpasa (IUC); 🇹🇷 Istanbul, Turkey