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

This study is currently recruiting participants.
Verified April 2017 by Kathryn J Swoboda, Massachusetts General Hospital
Sponsor:
ClinicalTrials.gov Identifier:
NCT02831296
First Posted: July 13, 2016
Last Update Posted: April 19, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborators:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
University of Utah
University of Massachusetts, Worcester
ARUP Laboratories
Newborn Screening Translational Research Network
American College of Medical Genetics and Genomics
Children's Hospital Medical Center, Cincinnati
Information provided by (Responsible Party):
Kathryn J Swoboda, Massachusetts General Hospital
  Purpose
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.

Condition
Spinal Muscular Atrophy

Study Type: Observational [Patient Registry]
Study Design: Observational Model: Case-Control
Time Perspective: Prospective
Target Follow-Up Duration: 10 Years
Official Title: Prospective Evaluation of Infants With Spinal Muscular Atrophy: SPOT SMA

Resource links provided by NLM:


Further study details as provided by Kathryn J Swoboda, Massachusetts General Hospital:

Primary Outcome Measures:
  • 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) ]

Secondary Outcome Measures:
  • 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

  • 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

  • WHO Motor Milestones [ Time Frame: At each visit (every 1-6 months depending on age) ]
    Acquisition of gross motor milestones, per WHO guidelines

  • 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

  • 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

  • Body composition [ Time Frame: Every 6 months ]
    DEXA scans

  • Bone density [ Time Frame: Every 6 months ]
    DEXA scans

  • Need for tube feeding [ Time Frame: 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) ]

Biospecimen Retention:   Samples With DNA
DNA, RNA and specific biomarker assessments for whole blood SMN protein levels, plasma and serum for exploratory metabolomics profiling, skin biopsy for fibroblast cell line establishment (iPS cell line studies)

Estimated Enrollment: 200
Study Start Date: February 2016
Estimated Primary Completion Date: March 2022 (Final data collection date for primary outcome measure)
Groups/Cohorts
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.


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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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
Criteria

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:

  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02831296


Contacts
Contact: Kendall Trautman 617-724-2523 ktrautman@mgh.harvard.edu
Contact: Gisel Dannehl 617-643-6451 gdannehl@mgh.harvard.edu

Locations
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Kendall Trautman    617-724-2523    ktrautman@mgh.harvard.edu   
Contact: Gisel Dannehl    617-643-6451    gdannehl@mgh.harvard.edu   
Principal Investigator: Kathryn J Swoboda, MD         
Sponsors and Collaborators
Massachusetts General Hospital
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
University of Utah
University of Massachusetts, Worcester
ARUP Laboratories
Newborn Screening Translational Research Network
American College of Medical Genetics and Genomics
Children's Hospital Medical Center, Cincinnati
Investigators
Principal Investigator: Kathryn J Swoboda, MD Massachusetts General Hospital
  More Information

Additional Information:
Publications:

Responsible Party: Kathryn J Swoboda, Katherine B. Sims MD Endowed Chair in Neurogenetics, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT02831296     History of Changes
Other Study ID Numbers: 2015P001934
R01HD069045 ( U.S. NIH Grant/Contract )
First Submitted: July 1, 2016
First Posted: July 13, 2016
Last Update Posted: April 19, 2017
Last Verified: April 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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 large-scale human genomic data as well as relevant associated data (e.g., phenotype and exposure 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.


Keywords provided by Kathryn J Swoboda, Massachusetts General Hospital:
SMA
Werdnig-Hoffmann disease
Kugelberg-Welander disease

Additional relevant MeSH terms:
Atrophy
Muscular Atrophy
Muscular Atrophy, Spinal
Pathological Conditions, Anatomical
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Spinal Cord Diseases
Central Nervous System Diseases
Motor Neuron Disease
Neurodegenerative Diseases
Neuromuscular Diseases