Prospective Evaluation of Infants With Spinal Muscular Atrophy:

NCT02831296 | Unknown DMC

• 2 other identifiers: 2015P001934R01HD069045
• Study Type: observational
• Target: 1,000
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Spinal Muscular Atrophy

Keywords

SMA; Werdnig-Hoffmann disease; Kugelberg-Welander disease

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• Maximum Ulnar CMAP Amplitude

  At each visit (every 1-6 months depending on age)

• CHOP-INTEND

  At each visit (every 1-6 months depending on age, or until deemed no longer appropriate by PI/physical therapist)

• WHO Motor Milestones

  At each visit (every 1-6 months depending on age)

• Hammersmith Functional Motor Scale - Expanded

  At each visit (every 1-6 months depending on age, beginning when deemed appropriate by PI/physical therapist)

• Hammersmith Infant Neurological Exam (HINE)

  At each visit (every 1-6 months depending on age, beginning when deemed appropriate by PI/physical therapist)

Study Arms (4)

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.

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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

You may qualify if:

• 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

You may not qualify if:

• None

Sponsors & Collaborators

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

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Related Publications (22)

• Bitton A, Martin C, Landon BE. A nationwide survey of patient centered medical home demonstration projects. J Gen Intern Med. 2010 Jun;25(6):584-92. doi: 10.1007/s11606-010-1262-8.

  PMID: 20467907 BACKGROUND

• Butchbach ME, Rose FF Jr, Rhoades S, Marston J, McCrone JT, Sinnott R, Lorson CL. Effect of diet on the survival and phenotype of a mouse model for spinal muscular atrophy. Biochem Biophys Res Commun. 2010 Jan 1;391(1):835-40. doi: 10.1016/j.bbrc.2009.11.148. Epub 2009 Nov 27.

  PMID: 19945425 BACKGROUND

• Butchbach ME, Singh J, Thorsteinsdottir M, Saieva L, Slominski E, Thurmond J, Andresson T, Zhang J, Edwards JD, Simard LR, Pellizzoni L, Jarecki J, Burghes AH, Gurney ME. Effects of 2,4-diaminoquinazoline derivatives on SMN expression and phenotype in a mouse model for spinal muscular atrophy. Hum Mol Genet. 2010 Feb 1;19(3):454-67. doi: 10.1093/hmg/ddp510. Epub 2009 Nov 6.

  PMID: 19897588 BACKGROUND

• Chung BH, Wong VC, Ip P. Spinal muscular atrophy: survival pattern and functional status. Pediatrics. 2004 Nov;114(5):e548-53. doi: 10.1542/peds.2004-0668. Epub 2004 Oct 18.

  PMID: 15492357 BACKGROUND

• Cobben JM, Lemmink HH, Snoeck I, Barth PA, van der Lee JH, de Visser M. Survival in SMA type I: a prospective analysis of 34 consecutive cases. Neuromuscul Disord. 2008 Jul;18(7):541-4. doi: 10.1016/j.nmd.2008.05.008. Epub 2008 Jun 24.

  PMID: 18579378 BACKGROUND

• Lefebvre S, Burglen L, Reboullet S, Clermont O, Burlet P, Viollet L, Benichou B, Cruaud C, Millasseau P, Zeviani M, et al. Identification and characterization of a spinal muscular atrophy-determining gene. Cell. 1995 Jan 13;80(1):155-65. doi: 10.1016/0092-8674(95)90460-3.

  PMID: 7813012 BACKGROUND

• Lemoine TJ, Swoboda KJ, Bratton SL, Holubkov R, Mundorff M, Srivastava R. Spinal muscular atrophy type 1: are proactive respiratory interventions associated with longer survival? Pediatr Crit Care Med. 2012 May;13(3):e161-5. doi: 10.1097/PCC.0b013e3182388ad1.

  PMID: 22198810 BACKGROUND

• Lorson CL, Hahnen E, Androphy EJ, Wirth B. A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy. Proc Natl Acad Sci U S A. 1999 May 25;96(11):6307-11. doi: 10.1073/pnas.96.11.6307.

  PMID: 10339583 BACKGROUND

• Mailman MD, Heinz JW, Papp AC, Snyder PJ, Sedra MS, Wirth B, Burghes AH, Prior TW. Molecular analysis of spinal muscular atrophy and modification of the phenotype by SMN2. Genet Med. 2002 Jan-Feb;4(1):20-6. doi: 10.1097/00125817-200201000-00004.

  PMID: 11839954 BACKGROUND

• Mannaa MM, Kalra M, Wong B, Cohen AP, Amin RS. Survival probabilities of patients with childhood spinal muscle atrophy. J Clin Neuromuscul Dis. 2009 Mar;10(3):85-9. doi: 10.1097/CND.0b013e318190310f.

  PMID: 19258855 BACKGROUND

• Oskoui M, Levy G, Garland CJ, Gray JM, O'Hagen J, De Vivo DC, Kaufmann P. The changing natural history of spinal muscular atrophy type 1. Neurology. 2007 Nov 13;69(20):1931-6. doi: 10.1212/01.wnl.0000290830.40544.b9.

  PMID: 17998484 BACKGROUND

• Rudnik-Schoneborn S, Berg C, Zerres K, Betzler C, Grimm T, Eggermann T, Eggermann K, Wirth R, Wirth B, Heller R. Genotype-phenotype studies in infantile spinal muscular atrophy (SMA) type I in Germany: implications for clinical trials and genetic counselling. Clin Genet. 2009 Aug;76(2):168-78. doi: 10.1111/j.1399-0004.2009.01200.x.

  PMID: 19780763 BACKGROUND

• Stange KC, Nutting PA, Miller WL, Jaen CR, Crabtree BF, Flocke SA, Gill JM. Defining and measuring the patient-centered medical home. J Gen Intern Med. 2010 Jun;25(6):601-12. doi: 10.1007/s11606-010-1291-3.

  PMID: 20467909 BACKGROUND

• Stille C, Turchi RM, Antonelli R, Cabana MD, Cheng TL, Laraque D, Perrin J; Academic Pediatric Association Task Force on Family-Centered Medical Home. The family-centered medical home: specific considerations for child health research and policy. Acad Pediatr. 2010 Jul-Aug;10(4):211-7. doi: 10.1016/j.acap.2010.05.002. No abstract available.

  PMID: 20605546 BACKGROUND

• Swoboda KJ, Prior TW, Scott CB, McNaught TP, Wride MC, Reyna SP, Bromberg MB. Natural history of denervation in SMA: relation to age, SMN2 copy number, and function. Ann Neurol. 2005 May;57(5):704-12. doi: 10.1002/ana.20473.

  PMID: 15852397 BACKGROUND

• Swoboda KJ, Kissel JT, Crawford TO, Bromberg MB, Acsadi G, D'Anjou G, Krosschell KJ, Reyna SP, Schroth MK, Scott CB, Simard LR. Perspectives on clinical trials in spinal muscular atrophy. J Child Neurol. 2007 Aug;22(8):957-66. doi: 10.1177/0883073807305665.

  PMID: 17761650 BACKGROUND

• Swoboda KJ, Scott CB, Reyna SP, Prior TW, LaSalle B, Sorenson SL, Wood J, Acsadi G, Crawford TO, Kissel JT, Krosschell KJ, D'Anjou G, Bromberg MB, Schroth MK, Chan GM, Elsheikh B, Simard LR. Phase II open label study of valproic acid in spinal muscular atrophy. PLoS One. 2009;4(5):e5268. doi: 10.1371/journal.pone.0005268. Epub 2009 May 14.

  PMID: 19440247 BACKGROUND

• Swoboda KJ. Seize the day: Newborn screening for SMA. Am J Med Genet A. 2010 Jul;152A(7):1605-7. doi: 10.1002/ajmg.a.33519. No abstract available.

  PMID: 20583173 BACKGROUND

• Wan L, Battle DJ, Yong J, Gubitz AK, Kolb SJ, Wang J, Dreyfuss G. The survival of motor neurons protein determines the capacity for snRNP assembly: biochemical deficiency in spinal muscular atrophy. Mol Cell Biol. 2005 Jul;25(13):5543-51. doi: 10.1128/MCB.25.13.5543-5551.2005.

  PMID: 15964810 BACKGROUND

• Wirth B, Brichta L, Schrank B, Lochmuller H, Blick S, Baasner A, Heller R. Mildly affected patients with spinal muscular atrophy are partially protected by an increased SMN2 copy number. Hum Genet. 2006 May;119(4):422-8. doi: 10.1007/s00439-006-0156-7. Epub 2006 Mar 1.

  PMID: 16508748 BACKGROUND

• Zerres K, Rudnik-Schoneborn S. Natural history in proximal spinal muscular atrophy. Clinical analysis of 445 patients and suggestions for a modification of existing classifications. Arch Neurol. 1995 May;52(5):518-23. doi: 10.1001/archneur.1995.00540290108025.

  PMID: 7733848 BACKGROUND

• Kolb SJ, Coffey CS, Yankey JW, Krosschell K, Arnold WD, Rutkove SB, Swoboda KJ, Reyna SP, Sakonju A, Darras BT, Shell R, Kuntz N, Castro D, Iannaccone ST, Parsons J, Connolly AM, Chiriboga CA, McDonald C, Burnette WB, Werner K, Thangarajh M, Shieh PB, Finanger E, Cudkowicz ME, McGovern MM, McNeil DE, Finkel R, Kaye E, Kingsley A, Renusch SR, McGovern VL, Wang X, Zaworski PG, Prior TW, Burghes AH, Bartlett A, Kissel JT; NeuroNEXT Clinical Trial Network and on behalf of the NN101 SMA Biomarker Investigators. Baseline results of the NeuroNEXT spinal muscular atrophy infant biomarker study. Ann Clin Transl Neurol. 2016 Jan 21;3(2):132-45. doi: 10.1002/acn3.283. eCollection 2016 Feb.

  PMID: 26900585 BACKGROUND

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)

MeSH Terms

Conditions

Muscular Atrophy, Spinal; Spinal Muscular Atrophies of Childhood

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; Neuromuscular Diseases; Heredodegenerative Disorders, Nervous System; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Kathryn J Swoboda, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Maria S Herrmann, MD

CONTACT

617-312-8318; msherrmann@mgh.harvard.edu

Emma Rodrigues

CONTACT

617-726-2996; erodrigues3@mgh.harvard.edu

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Target Duration: 10 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Katherine B. Sims MD Endowed Chair in Neurogenetics

Study Record Dates

• First Submitted: July 1, 2016
• First Posted: July 13, 2016
• Study Start: February 1, 2016
• Primary Completion: March 1, 2022
• Last Updated: September 2, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR

Locations

US (1)