Prospective Study of the Natural History of Patients With Type 2 and 3 Spinal Muscular Atrophy (NatHis-SMA)

• ClinicalTrials.gov Identifier: NCT02391831
• Recruitment Status: Completed
• First Posted: March 18, 2015
• Last Update Posted: July 19, 2018
• Sponsor: Institut de Myologie, France
• Collaborator: Institut Roche
• Information provided by (Responsible Party): Institut de Myologie, France

Tracking Information

• First Submitted Date: March 2, 2015
• First Posted Date: March 18, 2015
• Last Update Posted Date: July 19, 2018
• Study Start Date: May 2015
• Actual Primary Completion Date: June 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 12, 2015)

• Change from baseline of muscle strength [ Time Frame: Baseline and then every 6 months until end of the study, up to 24 months ]
  Study-specific assessments: Grip and pinch strength
• Change from baseline of motor function [ Time Frame: Baseline and then every 6 months until end of the study, up to 24 months ]
  Study-specific assessments: Moviplate and MFM scores, upper extremity functional reaching volume, timed tests (time to rise from floor, time to walk 10 meters, time to climb and descend stairs, distance walked on the Six-Minute Walk Test)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 12, 2015)

• Change from baseline of respiratory function [ Time Frame: Baseline and then every 6 months until end of the study, up to 24 months ]
  Study-specific assessments: Pulmonary function tests
• Change from baseline of physical activity of upper limbs movements [ Time Frame: Baseline and then every 6 months until end of the study, up to 24 months ]
  Quantity and duration of movements, time of inactivity during the day
• Change from baseline of skeletal muscle nuclear magnetic resonance (NMR) imaging (MRI) [ Time Frame: Baseline and then every 12 months until the end of the study, up to 24 months ]
  Muscle volume changes, intramuscular fatty infiltration progression, indices of disease activity (only for Paris and Strasbourg sites and for patients older than 4 years)
• Change from baseline of electrophysiology measurements [ Time Frame: Baseline and then every 6 months until end of the study, up to 24 months ]
  Compound Motor Action Potential (CMAP) Amplitude and Decrement search
• Change from baseline of Biomarkers of SMA progression [ Time Frame: Baseline and then every 6 months until end of the study, up to 24 months ]
  SMN mRNA and protein analysis, SMA exploratory biomarkers (e.g. mRNA, DNA profiling, RNA profiling, proteomic profiling)

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Prospective Study of the Natural History of Patients With Type 2 and 3 Spinal Muscular Atrophy
• Official Title: Prospective Study of the Natural History of Patients With Type 2 and 3 Spinal Muscular Atrophy
• Brief Summary: NatHis-SMA is a prospective, longitudinal and interventional study of the natural history of patients with type 2 and 3 Spinal Muscular Atrophy (SMA). The purpose of this study is to characterize the disease course over 2 years and identify prognostic variables of the disease and biomarkers of SMA progression, as well as determine the best outcome measures for further therapeutics approaches.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Basic Science

Condition

• Type 2 Spinal Muscular Atrophy
• Type 3 Spinal Muscular Atrophy

Intervention

• Other: Strength, function and activity measurements
• Other: Muscle MRI
• Other: Electrophysiology measurements
• Other: Blood sampling for biomarker analysis

• Study Arms: Not Provided
• Publications *: Chabanon A, Seferian AM, Daron A, Pereon Y, Cances C, Vuillerot C, De Waele L, Cuisset JM, Laugel V, Schara U, Gidaro T, Gilabert S, Hogrel JY, Baudin PY, Carlier P, Fournier E, Lowes LP, Hellbach N, Seabrook T, Toledano E, Annoussamy M, Servais L; NatHis-SMA study group. Prospective and longitudinal natural history study of patients with Type 2 and 3 spinal muscular atrophy: Baseline data NatHis-SMA study. PLoS One. 2018 Jul 26;13(7):e0201004. doi: 10.1371/journal.pone.0201004. eCollection 2018.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 11, 2016): 81
• Original Estimated Enrollment (submitted: March 12, 2015): 70
• Actual Study Completion Date: June 2018
• Actual Primary Completion Date: June 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

INCLUSION CRITERIA

• Type 2 or 3 spinal muscular atrophy genetically confirmed
• Age superior or equal to 2 years old up to 30 years of age included
• For patients older than 6 years old, willing and able to comply with all protocol requirements and procedures.
• For non-ambulant patients, able to sit upright in a wheelchair for at least three hours
• Patients over 18 years of age and parent(s)/legal guardian(s) of patients < 18 years of age must provide written informed consent prior to participating in the study and informed assent will be obtained from minors at least 7 years of age when required by regulation.
• In France only: Affiliated to or a beneficiary of a social security category

EXCLUSION CRITERIA

• Previously treated with an investigational drug within 6 months prior the recruitment in this study.
• Other condition which may significantly interfere with the assessment of the SMA and is clearly not related to the disease
• Current or anticipated participation in any therapeutic investigational clinical studies.
• Patients with specific contraindication to MRI (i.e. metallic foreign body, claustrophobia, and others deemed to be prohibitive by the investigators) will be allowed to participate, but MRI will not be performed.
• For women : pregnancy or current breastfeeding

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 2 Years to 30 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, France, Germany

Administrative Information

• NCT Number: NCT02391831
• Other Study ID Numbers: NatHis-SMA; IDRCB-2014-A01263-44 ( Other Identifier: ANSM (French Regulatory Authority) )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Institut de Myologie, France
• Original Responsible Party: Same as current
• Current Study Sponsor: Institut de Myologie, France
• Original Study Sponsor: Same as current
• Collaborators: Institut Roche

Investigators

• Principal Investigator: Laurent Servais, MD; Association Institut de Myologie

• PRS Account: Institut de Myologie, France
• Verification Date: July 2018