Prospective Evaluation of Infants With Spinal Muscular Atrophy:

Study Overview
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Brief Summary
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SPOT SMA is a prospective NIH-supported clinical study targeting pre-symptomatic or recently diagnosed infants and children with Spinal Muscular Atrophy (SMA) types 1, 2, or 3 and their healthy control siblings less than 36 months of age at the time of study enrollment. The main objective of the study is to prospectively collect longitudinal clinical outcomes and provide counseling and education to parents of newly diagnosed children. The study will assess the impact of current standard of care management paradigms and interventions on health outcomes in newly diagnosed SMA infants and children with type 1, 2 or 3 and age appropriate controls. There is no investigational drug and no specific intervention in this study. Rather, the investigators will document outcomes related to current therapies provided to participating subjects, and will educate participants about possible clinical trial opportunities.

Detailed Description
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Overview of data to be collected from enrolled infants followed longitudinally and entered into the NBSTRN Longitudinal Pediatric Data Resource Past medical history relevant to pregnancy, delivery, complications in the immediate neonatal period, birth parameters, family history and any medical problems other than SMA (ie prematurity, etc) Ongoing medical history indicating problems related to the following areas: feeding, growth, respiratory status including use of cough assist and bilevel respiratory support, gastrointestinal issues, cardiac symptoms, neurologic symptoms or signs including muscle weakness, hospitalizations, ER visits, other adverse events Assessment of dietary intake and use of nutritional supplements Surgical history and ongoing documentation of assessments and need for g-tube, Nissen, tympanostomy, adenoidectomy/tonsillectomy or other airway surgeries, and orthopedic procedures Caregiver obtained developmental history and documentation of newly acquired and/or loss of previously acquired gross motor skills at the time of each visit Documentation of caregiver reported outcomes Documentation of anthropometric measures, vital signs, general physical examination parameters Neurological examination using standardized tools Time to death, permanent invasive ventilation and/or need for > 16 hours/day of bilevel respiratory support Specific assessment of motor function as measured using age appropriate motor outcome measures such as: the Children's Hospital of Philadelphia Infant Tests of Neuromuscular Disorders (CHOP-INTEND), Test of Infant Motor Performance Screening Inventory, WHO motor milestones or others, and Hammersmith Functional Motor Scale for SMA Expanded for children 18 months and older Electrophysiologic studies such as maximum ulnar compound muscle action potential (CMAP) amplitude and area Documentation of range of motion, development of limb contractures and/or presence of scoliosis, lordosis, hip dysplasia or other orthopedic outcomes Additional optional exploratory biomarker assessments DEXA measurements to assess body composition and bone density The option to enroll in an autopsy study at the time of death to contribute samples to a research biorepository Normal control subjects such as unaffected siblings will undergo these same measurements, as applicable. Unaffected parents' participation will be limited to collection and banking of blood and cell lines.

Official Title
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Prospective Evaluation of Infants With Spinal Muscular Atrophy: SPOT SMA

Conditions
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Spinal Muscular Atrophy

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For affected subjects: genetic diagnosis of SMA For unaffected family members: parent or sibling of any age (without genetic diagnosis of SMA) of affected subject enrolled in study Exclusion Criteria: None
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Affected Subjects <36 Mos. of Age<br>Infants and children 36 months of age and younger at time of enrollment who have been genetically diagnosed with Spinal Muscular Atrophy (SMA) The affected cohort will receive coordinated, multidisciplinary care including dietary intervention, respiratory monitoring, physical therapy, and genetic counseling. They will also undergo assessment of motor function, muscle action potential measurement, and body composition, as well as blood sample collection for DNA and biomarkers, and optional research skin biopsy. | |
| Unaffected Subjects <36 Mos. of Age<br>Infants and children 36 months of age and younger who are not affected with SMA The unaffected group will undergo the same assessments as the affected group. | |
| Unaffected Family Members<br>Parents and siblings of any age, without genetic diagnosis of SMA, who have family members enrolled in either of the Affected Infants/Children/Adults cohorts. The unaffected siblings will undergo the same assessments as the affected group, where age-appropriate. Unaffected parents' participation will be limited to blood sample collection and optional research skin biopsy. | |
| Affected Subjects >36 Mos. of Age<br>Children and adults >36 months at time of enrollment who have been genetically diagnosed with Spinal Muscular Atrophy. The older affected cohort will receive coordinated, multidisciplinary care including dietary intervention, respiratory monitoring, physical therapy, and genetic counseling. They will also undergo assessment of motor function, muscle action potential measurement, and body composition, as well as blood sample collection for DNA and biomarkers, and optional research skin biopsy. Where applicable, these participants will be considered Affected Control Subjects. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to death and/or full time invasive ventilation or need for > 16 hours/day of bilevel respiratory support |  | At each visit (every 1-6 months depending on age) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Ulnar CMAP Amplitude | Maximum ulnar compound muscle action potential (CMAP) amplitude and area | At each visit (every 1-6 months depending on age) | 
| CHOP-INTEND | Assessment of motor function in infants and children functioning at an infant level | At each visit (every 1-6 months depending on age, or until deemed no longer appropriate by PI/physical therapist) | 
| WHO Motor Milestones | Acquisition of gross motor milestones, per WHO guidelines | At each visit (every 1-6 months depending on age) | 
| Hammersmith Functional Motor Scale - Expanded | Assessment of motor function in subjects whose motor function exceeds that of an infant | At each visit (every 1-6 months depending on age, beginning when deemed appropriate by PI/physical therapist) | 
| Hammersmith Infant Neurological Exam (HINE) | Assessment of neuromotor function in infants, general neurologic exam in infants | At each visit (every 1-6 months depending on age, beginning when deemed appropriate by PI/physical therapist) | 
| Body composition | DEXA scans | Every 6 months | 
| Bone density | DEXA scans | Every 6 months | 
| Need for tube feeding |  | At each visit (every 1-6 months depending on age) | 
| Caregiver Questionnaire total score and subscores |  | At each visit (every 1-3 months depending on age and SMA type) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SMA, Werdnig-Hoffmann disease, Kugelberg-Welander disease