Prospective Evaluation of Infants With Spinal Muscular Atrophy: (SPOTSMA)

August 31, 2020 updated by: Kathryn J Swoboda, Massachusetts General Hospital

Prospective Evaluation of Infants With Spinal Muscular Atrophy: SPOT SMA

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.

Study Overview

Status

Unknown

Conditions

Detailed Description

Overview of data to be collected from enrolled infants followed longitudinally and entered into the NBSTRN Longitudinal Pediatric Data Resource

  1. 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)

  2. 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

  3. Assessment of dietary intake and use of nutritional supplements
  4. Surgical history and ongoing documentation of assessments and need for g-tube, Nissen, tympanostomy, adenoidectomy/tonsillectomy or other airway surgeries, and orthopedic procedures
  5. Caregiver obtained developmental history and documentation of newly acquired and/or loss of previously acquired gross motor skills at the time of each visit
  6. Documentation of caregiver reported outcomes
  7. Documentation of anthropometric measures, vital signs, general physical examination parameters
  8. Neurological examination using standardized tools
  9. Time to death, permanent invasive ventilation and/or need for > 16 hours/day of bilevel respiratory support
  10. 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
  11. Electrophysiologic studies such as maximum ulnar compound muscle action potential (CMAP) amplitude and area
  12. Documentation of range of motion, development of limb contractures and/or presence of scoliosis, lordosis, hip dysplasia or other orthopedic outcomes
  13. Additional optional exploratory biomarker assessments
  14. DEXA measurements to assess body composition and bone density
  15. 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.

Study Type

Observational

Enrollment (Anticipated)

1000

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Kathryn J Swoboda, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Pre-symptomatic or newly diagnosed infants and children with Spinal Muscular Atrophy (SMA) types 1, 2, or 3; OR unaffected parents and siblings of enrolled infants and children with SMA; OR control subjects: infants and children who are not affected with SMA

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Affected Subjects <36 Mos. of Age

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

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

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

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?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum Ulnar CMAP Amplitude
Time Frame: At each visit (every 1-6 months depending on age)
Maximum ulnar compound muscle action potential (CMAP) amplitude and area
At each visit (every 1-6 months depending on age)
CHOP-INTEND
Time Frame: At each visit (every 1-6 months depending on age, or until deemed no longer appropriate by PI/physical therapist)
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
Time Frame: At each visit (every 1-6 months depending on age)
Acquisition of gross motor milestones, per WHO guidelines
At each visit (every 1-6 months depending on age)
Hammersmith Functional Motor Scale - Expanded
Time Frame: At each visit (every 1-6 months depending on age, beginning when deemed appropriate by PI/physical therapist)
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)
Time Frame: At each visit (every 1-6 months depending on age, beginning when deemed appropriate by PI/physical therapist)
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
Time Frame: Every 6 months
DEXA scans
Every 6 months
Bone density
Time Frame: Every 6 months
DEXA scans
Every 6 months
Need for tube feeding
Time Frame: At each visit (every 1-6 months depending on age)
At each visit (every 1-6 months depending on age)
Caregiver Questionnaire total score and subscores
Time Frame: At each visit (every 1-3 months depending on age and SMA type)
At each visit (every 1-3 months depending on age and SMA type)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Massachusetts General Hospital

Collaborators

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Children's Hospital Medical Center, Cincinnati
University of Utah
University of Massachusetts, Worcester
ARUP Laboratories
Newborn Screening Translational Research Network
American College of Medical Genetics and Genomics

Investigators

  • Principal Investigator: Kathryn J Swoboda, MD, Massachusetts General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2016

Primary Completion (Anticipated)

March 1, 2022

Study Registration Dates

First Submitted

July 1, 2016

First Submitted That Met QC Criteria

July 8, 2016

First Posted (Estimate)

July 13, 2016

Study Record Updates

Last Update Posted (Actual)

September 2, 2020

Last Update Submitted That Met QC Criteria

August 31, 2020

Last Verified

August 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2015P001934
  • R01HD069045 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

The National Institute of Child Health and Human Development has a contract with the American College of Medical Genomics and the Newborn Screening Translational Research Network (NBSTRN) in collaboration with the bioinformatics group at the Cincinnati Children's Hospital to develop a national database for data capture and management for all the follow-up data to be collected for those who agree to participate in the research study. The investigators will share deidentified data with the NBSTRN database.

The investigators will also submit relevant associated data (e.g., phenotype data) to an NIH-designated data repository in a timely manner, as indicated by the NIH Genomic Data Sharing policy.

Aggregate Data will be available for submission/general research use.

IPD Sharing Supporting Information Type

  • Clinical Study Report (CSR)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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