Prospective Evaluation of Infants With Spinal Muscular Atrophy:

Spinal Muscular Atrophy Clinical Trial

— SPOTSMA  

Official title:

Prospective Evaluation of Infants With Spinal Muscular Atrophy: SPOT SMA

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02831296
• Other study ID #: 2015P001934
• Secondary ID: R01HD069045
• Status: Recruiting
• Start date: February 2016

Study information

• Verified date: August 2020
• Source: Massachusetts General Hospital
• Contact: Maria S Herrmann, MD
• Phone: 617-312-8318
• Email: msherrmann[@]mgh.harvard.edu
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. primary completion date: March 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Atrophy
• Muscular Atrophy
• Muscular Atrophy, Spinal
• Spinal Muscular Atrophy

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (8)

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

Country where clinical trial is conducted

United States, 

References & 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. — View Citation

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. — View Citation

Butchbach ME, Singh J, Thorsteinsdóttir M, Saieva L, Slominski E, Thurmond J, Andrésson 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. — View Citation

Chung BH, Wong VC, Ip P. Spinal muscular atrophy: survival pattern and functional status. Pediatrics. 2004 Nov;114(5):e548-53. Epub 2004 Oct 18. — View Citation

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. — View Citation

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. — View Citation

Lefebvre S, Bürglen 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Rudnik-Schöneborn 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. — View Citation

Stange KC, Nutting PA, Miller WL, Jaén 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. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Wirth B, Brichta L, Schrank B, Lochmüller 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. Epub 2006 Mar 1. — View Citation

Zerres K, Rudnik-Schöneborn 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. — View Citation

* Note: There are 22 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Maximum Ulnar CMAP Amplitude	Maximum ulnar compound muscle action potential (CMAP) amplitude and area	At each visit (every 1-6 months depending on age)
Secondary	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)
Secondary	WHO Motor Milestones	Acquisition of gross motor milestones, per WHO guidelines	At each visit (every 1-6 months depending on age)
Secondary	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)
Secondary	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)
Secondary	Body composition	DEXA scans	Every 6 months
Secondary	Bone density	DEXA scans	Every 6 months
Secondary	Need for tube feeding		At each visit (every 1-6 months depending on age)
Secondary	Caregiver Questionnaire total score and subscores		At each visit (every 1-3 months depending on age and SMA type)

External Links

•   Medical Home Portal, University of Utah Department of Pediatrics