About this trial
5q-spinal muscular atrophy (5q-SMA) is a rare, autosomal recessive neuromuscular disease characterized by degeneration of motor neurons in the spinal cord and lower brainstem with progressive muscle atrophy, weakness, and paralysis. The incidence is 1 in 7-10,000 live births. 5q-SMA presents a wide range of phenotypes that are classified into five clinical groups depending on age of onset and maximum motor milestone achieved. SMA type 1 presents shortly after birth and before six months of age with inability to achieve independent sitting and limited life expectancy due to respiratory complications (high mortality rate by 2 years of age). In addition to the severe gross-motor and respiratory impairment, bulbar weakness and dysfunction represent an obstacle to the development of verbal skills in these patients. To date, very little is known about these functions in children with SMA 1. With the increasing number of long-term SMA 1 survivors worldwide thanks to the availability of new pharmacological treatments, it has become obvious that treated children show new phenotypes, presenting changes not only in motor and respiratory function, but also in other domains, including bulbar function, speech and communication development. We aim to investigate the evolution of bulbar function and speech/communication development in children with SMA type 1 treated with approved disease-modifying therapies through validate scales and questionnaires for the paediatric population. Additional neurophysiological and neuroimaging studies will be offered on an optional basis to further investigate the underlying brain electrical activity, and brain structural and functional organization. The information gathered would promote the definition of additional outcome measures capturing improvement at these levels. A better understanding of the development of these areas would help to plan SMA 1- tailored supportive programs provided by speech and language therapists, thus enhancing the current recommendations for management in SMA.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
genetic documentation of 5q SMA;
onset of clinical signs and symptoms at ≤ 6 months (180 days) of age;
0 - 18 years of age
treatment with any of the approved disease-modifying therapies;
Disqualifiers
any clinically significant medical finding that - in the judgment of the Investigator - will make the patient unsuitable for participation in, and/or unable to complete the study procedures;
parent(s)/legal guardian(s) unable or unwilling to comply with study procedures and/or refuses to sign consent form.
any clinically significant medical finding that - in the judgment of the Investigator - will make the patient unsuitable for participation in, and/or unable to complete the study procedures;
parent(s)/legal guardian(s) unable or unwilling to comply with study procedures and/or refuses to sign consent form.
Trial population
In the first instance, we will recruit SMA 1 paediatric patients (up to 18 years of age) who are under the care of the Neuromuscular team at the Dubowitz Neuromuscular Centre, London, UK, and who are being treated with any approved disease-modifying therapies. A total number of 30 patients is expected to be enrolled in the pilot phase of the study.
Trial design
Case-only
Prospective
Treatments tested in this trial
Not listed
Trial groups
Trial outcomes
Primary outcomes
Bulbar function - Changes from baseline
Paediatric-Functional Oral Intake Scale (p-FOIS/CEDAS) Min score( Worse) - Max score 6 (Better performance)
Bulbar function
Paediatric-Functional Oral Intake Scale (p-FOIS/CEDAS) Min score 1( Worse) - Max score 6 (Better performance)
Bulbar function
Paediatric-Functional Oral Intake Scale (p-FOIS/CEDAS) Min score 1 (Worse) - Max score 6 (Better performance)
Bulbar function
Paediatric-Functional Oral Intake Scale (p-FOIS/CEDAS) Min score 1( Worse) - Max score 6 (Better performance)
Secondary outcomes
Cognitive function - Changes from baseline
Bayley Scales of Infant \& Toddler Development - Forth Edition Age-based standard scores (M = 100, SD = 15). Minimum value of normal range is 85, maximum value of normal range is 115, higher score means better outcome.
Cognitive function
Bayley Scales of Infant \& Toddler Development - Forth Edition Age-based standard scores (M = 100, SD = 15). Minimum value of normal range is 85, maximum value of normal range is 115, higher score means better outcome.
Cognitive function
Bayley Scales of Infant \& Toddler Development - Forth Edition Age-based standard scores (M = 100, SD = 15). Minimum value of normal range is 85, maximum value of normal range is 115, higher score means better outcome.
Cognitive function
Bayley Scales of Infant \& Toddler Development - Forth Edition Age-based standard scores (M = 100, SD = 15). Minimum value of normal range is 85, maximum value of normal range is 115, higher score means better outcome.
Sponsors and contacts
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Institute of Child Health
Lead sponsor
Great Ormond Street Hospital for Children NHS Foundation Trust
Collaborator