N/A
N=53
Spinal Muscular Atrophy (SMA) Biomarkers Study in the Immediate Postnatal Period of Development
Spinal Muscular Atrophy (SMA)
Bottom Line
View on ClinicalTrials.gov: NCT01736553 ↗Enrolled (actual)
53
Serious AEs
0.0%
Results posted
May 2018
Primary outcome: Primary: Motor Function Assessments- Test for Infant Motor Performance Screening Items (TIMPSI) — 36.06; 88.47; 40.54; 89.44 scores on a scale
Study Design & Population
- Study type
- Observational
- Phase
- N/A
- Interventions
- —
- Age
- Pediatric
- Sex
- All
- Sponsor
- Ohio State University
- Primary completion
- Sep 2015
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Motor Function Assessments- Test for Infant Motor Performance Screening Items (TIMPSI) |
36.06; 88.47; 40.54; 89.44; 32.03; 85.39 | — |
| PRIMARY Motor Function Assessments- The Children's Hospital of Philadelphia Infant Test for Neuromuscular Disorders (CHOP-INTEND) |
18.38; 13.18; 9.74; 7.52; 7.01 | — |
| PRIMARY Motor Function Assessments-Alberta Infant Motor Scale (AIMS) |
11.74; 19.29; 15.58; 34.10; 21.60; 37.10 | — |
| PRIMARY Putative Physiological Biomarker- Compound Motor Action Potential Testing (CMAP) |
1.07; 6.00; 0.51; 5.95; 0.49; 6.55 | — |
| PRIMARY Molecular Biomarkers- mRNA |
0.55; 1.29; 0.47; 1.21; 0.50; 1.11 | — |
| PRIMARY Molecular Biomarkers- SMN Protein Levels |
4798.85; 8325.96; 6719.63; 10247; 3108.79; 6635.90 | — |
| PRIMARY Putative Physiological Biomarkers-Weight |
6.88; 7.83; 7.92; 8.94; 8.71; 9.88 | — |
| PRIMARY Correlation of Biomarkers With Motor Function Tests for SMA Subjects- CMAP |
9.36; 17.25; 22.88; 21.53; 17.48; 18.57 | — |
| PRIMARY Correlation of Biomarkers With Motor Function Tests for SMA Subjects- mRNA |
53.60; 0.11; 125.52; 0.11; 181.22; 0.11 | — |
| PRIMARY Correlation of Biomarkers With Motor Function Tests for SMA Subjects- SMN Protein |
-0.0011; -0.0003; 0.00066; -0.0003; 0.026; -0.0003 | — |
| PRIMARY Correlation of Biomarkers With Motor Function Tests for SMA Subjects- Weight |
2.27; -2.39 | — |
| PRIMARY Correlation of Biomarkers With Motor Function Tests for Healthy Control Subjects- CMAP |
-0.23; 0.21; -4.52; 0.21; -0.58; 0.21 | — |
| PRIMARY Correlation of Biomarkers With Motor Function Tests for Healthy Control Subjects- mRNA |
9.52; -2.46 | — |
| PRIMARY Correlation of Biomarkers With Motor Function Tests for Healthy Control Subjects- Weight |
0.60; 1.48; 0.60; -0.72; 0.60; 1.14 | — |
| SECONDARY Biomarker Prediction of Risk of Death |
0.72; 0.94; 0.37; 0.28; 1.27; 0.02 | — |
| SECONDARY Motor Function Assessments- Test for Infant Motor Performance Screening Items (TIMPSI) SMN Copy Number =2 Cohort |
24.53; 88.25; 20.08; 89.20; 13.82; 85.15 | — |
| SECONDARY Motor Function Assessments- The Children's Hospital of Philadelphia Infant Test for Neuromuscular Disorders (CHOP-INTEND) SMN Copy Number =2 Cohort |
18.05; 12.87; 9.38; 7.33; 7.00 | — |
| SECONDARY Putative Physiological Biomarker- Compound Motor Action Potential Testing (CMAP) SMN Copy Number = 2 Cohort |
0.36; 5.95; 0.33; 5.92; 0.90; 6.49 | — |
| SECONDARY Molecular Biomarkers- mRNA SMA Copy Number = 2 Cohort |
0.46; 1.29; 0.38; 1.21; 0.29; 1.12 | — |
| SECONDARY Molecular Biomarkers- SMN Protein Levels SMA Copy Number = 2 |
3785.02; 8598.73; 5800.63; 10614; 1612.35; 6426.06 | — |
| SECONDARY Putative Physiological Biomarkers-Weight SMN Copy Number =2 Cohort |
6.63; 7.83; 7.70; 8.93; 8.51; 9.88 | — |
| SECONDARY Correlation of CMAP Biomarker With Motor Function Tests for SMA Subjects SMN Copy Number =2 Cohort |
5.10; 3.71 | — |
| SECONDARY Correlation of mRNA Biomarkers With Motor Function Tests for SMA Subjects SMN Copy Number =2 Cohort |
-6.39; 0.097 | — |
| SECONDARY Correlation of Protein Level Biomarkers With Motor Function Tests for SMA Subjects SMN Copy Number =2 Cohort |
0.000063; 0.00048 | — |
| SECONDARY Correlation of Biomarkers (Weight) With Motor Function Tests for SMA Subjects SMN Copy Number =2 Cohort |
-2.50; -2.43 | — |
Summary
Spinal muscular atrophy (SMA) is the leading genetic cause of death of infants. Strong preclinical evidence suggests that effective therapy must be delivered as early as possible to prevent progression of the disease. The primary study objective will be to identify prognostic and surrogate biomarkers of disease progression that will facilitate the execution of therapeutic SMA clinical trials in infants.
Eligibility Criteria
Inclusion Criteria
All infants will be between 0-6 months of age at the time of enrollment. Parents or guardians of the enrolled infants must sign an informed consent form prior to any study procedure being performed.
The infants with SMA must have already had a positive DNA test outside of the study to qualify for enrollment. An infant with SMA can have any number of SMN2 gene copies. Knowledge of the number of SMN2 gene copies prior to enrollment is not required.
Healthy control infants who meet the following criteria will be enrolled:
- Birth between 36 and 42 weeks inclusive of gestation
- Siblings of children with SMA must have had prior SMA genetic testing completed con-firming the infant is a healthy control
- Principal investigator feels the family/infant is able and willing to comply with study procedures
- Parent or guardian able to give informed consent
SMA infants who meet the following criteria will be enrolled:
- Birth between 36 and 42 weeks inclusive of gestation
- Positive SMN1 gene mutation/deletion
- Principal investigator feels the family/infant is able and willing to comply with study procedures
- Parent or guardian able to give informed consent
Exclusion Criteria
- Use of any putative therapy intended to increase the amount of SMN protein in cells
- Enrollment in an SMA therapeutic trial at the time of enrollment in the SMA biomarker study
- Have a systemic illness requiring ongoing treatment, such as pneumonia
- Clinically significant abnormal findings (as determined by the investigator) on the physical examination or medical history (including history of tracheostomy tubes and ventilator-dependency)
- Dependency upon non-invasive ventilatory support (ie: BiPAP) for more than 12 hours/day
Data sourced from ClinicalTrials.gov (NCT01736553). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.