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Monitoring to the Evolution of Motor Function in SMA Type II Adults Patients Treated With SPINRAZA® (SMAII)

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ClinicalTrials.gov Identifier: NCT04159987
Recruitment Status : Recruiting
First Posted : November 12, 2019
Last Update Posted : July 5, 2022
Sponsor:
Information provided by (Responsible Party):
Centre Hospitalier Universitaire de Nice

Brief Summary:
SPINRAZA® (Nusinersen) is the first intrathecal administered drug which was approved by the FDA to treat SMA children and adults (2016). The aim is to monitor the evolution of the Motor Function Measure-32 for SMA type II adult patients treated with SPINRAZA® (Nusinersen).

Condition or disease Intervention/treatment Phase
Spinal Muscular Atrophy Other: Spinraza intrathecal injection Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: A Multicenter, Interventional, Open-label Study to Monitor the Evolution of Motor Function in SMA Type II Adults Patients Treated With SPINRAZA®
Actual Study Start Date : February 25, 2020
Estimated Primary Completion Date : November 25, 2022
Estimated Study Completion Date : February 25, 2025


Arm Intervention/treatment
Experimental: Spinal muscular atrophy patient Other: Spinraza intrathecal injection
The aim is to monitor the evolution of the Motor Function Measure-32 for SMA type II adult patients treated with SPINRAZA® (Nusinersen).




Primary Outcome Measures :
  1. Change of the Motor Function Measure-32 (MFM-32) from Baseline (M0) to 1 month (M1), 3 months (M3), 7 months (M7), 15 months (M15) and 27 months (M27) [ Time Frame: at baseline, 1, 3, 7, 15 and 27 months ]

    Within MFM-32, 32 terms will be evaluated to describe patient's motor functions and grouped into 3 sub-scores at baseline (M0), M1, M3, M7, M15 and M27:

    • D1: standing position and transfer
    • D2: axial and proximal motor function
    • D3: distal motor function The MFM-32 ratings rely on the use of a 4-point Likert scale based on the subject's maximal abilities without assistance (0: cannot initiate the task or maintain the starting position; 1: performs the task partially; 2: performs the task incompletely or imperfectly; 3: performs the task fully and normally.)


Secondary Outcome Measures :
  1. Change of the pulmonary function, specially Force Vital Capacity (FVC%), from Baseline (M0) to 1 month (M1), 7 months (M7), 15 months (M15) and 27 months (M27) [ Time Frame: at baseline, 1, 3, 7, 15 and 27 months ]
    Force Vital Capacity (FVC%)will be measured in sitting position and optionally in lying position.

  2. Change of the pulmonary function, specially Maximal Inspiratory Pressure (MIP) from Baseline (M0) to 1 month (M1), 7 months (M7), 15 months (M15) and 27 months (M27) [ Time Frame: at baseline, 1, 3, 7, 15 and 27 months ]
    Maximal Inspiratory Pressure (MIP) will be measued in sitting position and optionally in lying position.

  3. Change of the pulmonary function, specially Maximum Expiratory Pressure (MEP) from Baseline (M0) to 1 month (M1), 7 months (M7), 15 months (M15) and 27 months (M27) [ Time Frame: at baseline, 1, 3, 7, 15 and 27 months ]
    Maximum Expiratory Pressure (MEP) will be measured in sitting position and optionally in lying position.

  4. Change of the Fatigue Severity Scale (FSS) from Baseline (M0) to 1 month (M1), 7 months (M7), 15 months (M15) and 27 months (M27) [ Time Frame: at baseline, 1, 3, 7, 15 and 27 months ]
    The FSS is a unidimensional scale which focuses on the physical aspects of fatigue. It is a self-reported questionnaire developed to measure the impact of disabling fatigue on daily functioning. It covers several areas including physical, social, and cognitive effects. The FSS is a patient-reported outcome composed of 9-items with scores ranging from 1 = "strongly disagree" to 7 = "strongly agree".

  5. Change of the Pinch and Grip test from Baseline (M0) to 1 month (M1), 7 months (M7), 15 months (M15) and 27 months (M27) [ Time Frame: at baseline, 1, 3, 7, 15 and 27 months ]
    The purpose of those tests is to measure the maximum isometric strength of the hand and forearm muscles when doing a grasping or a pinching action. The equipment required for the grip and the pinch tests is a calibrate dynamometer. The subject should be strongly encouraged to give a maximum effort. We record three trials for each hand, alternating hands with at least 30 seconds recovery between each effort. We keep the best result.

  6. Change of the Repeated nine-hole peg test (r9HPT) from Baseline (M0) to 1 month (M1), 7 months (M7), 15 months (M15) and 27 months (M27) [ Time Frame: at baseline, 1, 3, 7, 15 and 27 months ]

    The r9HPT is a modification of the 9-Hole Peg test (9HPT) targeting endurance instead of motor function. The 9HPT is a brief, standardized, quantitative test of upper extremity function.

    In r9HPT, participants performed 5 consecutive rounds of the 9HPT, without break, using the same and preferred hand. We will look at the change (ratio) in score between the last trial and the first trial, an increase in time needed to perform the test in consecutive rounds indicating the apparition of the muscle fatigability.


  7. Change of the Revised Hammersmith Scale (RHS) from Baseline (M0) to 1 month (M1), 7 months (M7), 15 months (M15) and 27 months (M27) [ Time Frame: at baseline, 1, 3, 7, 15 and 27 months ]
    The RHS consisted of 36 items for very weak SMA 2 through to very strong SMA 3. With regards scoring, 33 items were graded on an ordinal scale of 0, 1, 2 (where 0 denotes the least level of ability/function progressing to the highest level of ability to achieve a score of 2), the remaining 3 items were scored 0, 1 (where 0 is unable and 1 was able to achieve). The maximum achievable score is 69.

  8. Change of the Iowa Oral Performance Instrument (IOPI) from Baseline (M0) to 1 month (M1), 7 months (M7), 15 months (M15) and 27 months (M27 [ Time Frame: at baseline, 1, 3, 7, 15 and 27 months ]
    The Iowa Oral Performance Instrument (IOPI) is a means to quantify lip, tongue, and buccal strength using a validated tool with published ranges for normative data for lingual measurements

  9. Change of the Revised Upper Limb Module (RULM) from Baseline (M0) to 1 month (M1), 7 months (M7), 15 months (M15) and 27 months (M27 [ Time Frame: at baseline, 1, 3, 7, 15 and 27 months ]

    The RULM is a validated measure and used only for patients with SMA that evaluates shoulder, wrist, and hand functions. It takes approximately 15 minutes to administer and requires a toolkit that is used to have the patient repeat specific tasks (eg, picking up a coin, bringing hand to mouth) with both arms. RULM is a scale of 19 scorable items; each item is scored from 0 to 2:

    • 0=Unable
    • 1=Able, with modification
    • 2=Able, no difficulty The maximum score is 37 and the patients are scored on both upper limbs.

  10. Change of the Electrophysiological assessment, specially Motor Unit Number Index (MUNIX), from Baseline (M0) to 1 month (M1), 7 months (M7), 15 months (M15) and 27 months (M27) [ Time Frame: at baseline, 1, 3, 7, 15 and 27 months ]
    MUNIX is a neurophysiologic test which provide an index of functioning lower motor neurons in a muscle. MUNIX total score is calculated by adding the individual values of the 6 tested muscles (abductor pollicis brevis, abductor digiti minimi, first dorsal interosseous, deltoid, tibialis anterior and trapezius).

  11. Change of the Electrophysiological assessment, specially Motor Units Size Index (MUSIX), from Baseline (M0) to 1 month (M1), 7 months (M7), 15 months (M15) and 27 months (M27) [ Time Frame: at baseline, 1, 3, 7, 15 and 27 months ]
    MUSIX is a neurophysiologic tests which provide an index of functioning lower motor neurons in a muscle. MUSIX is calculated by dividing MUNIX by the Compound Motor Action Potential (CMAP) amplitude, measured in 6 tested muscles (abductor pollicis brevis, abductor digiti minimi, first dorsal interosseous, deltoid, tibialis anterior and trapezius).

  12. Change of the health Status from Baseline (M0) to 1 month (M1), 7 months (M7), 15 months (M15) and 27 months (M27 [ Time Frame: at baseline, 1, 3, 7, 15 and 27 months ]
    Health Status will be assessed using the question quality of Life in genetic Neuromuscular Disease (QoL-gNMD), specifically designed for patients with a slowly-progressive neuromuscular disease with genetic predominant muscular damage. The QoL-gNMD is splitted in 3 domains: "Impact of Physical Symptoms" (score from 0 to 19), "Self-perception" (score from 0 to 24) and "Activities and Social Participation" (score from 0 to 27).



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult patients with SMA type II disease who are wheelchair bound,
  • Must be 18 years or older,
  • Men or Women with SMA type II disease (age at symptoms onset: >6 months old and who never acquired the capacity to walk but acquired the ability to sit without support) with genetic confirmed diagnosis of 5q SMA homozygous gene deletion (SMN1 exon 7/8) or mutation or compound heterozygous mutation - performed by PCR amplification and restriction digest of DNA using primers flanking SMN1 and SMN2 exon 7.
  • MFM 32 score ≥ 19/96
  • Lumbar CT scan showing the feasibility of intrathecal injection.
  • Written informed consent from the subject prior to initiation of any study-mandated procedures
  • Females of childbearing potential must have a negative pregnancy test at Screening and at Enrollment, must agree to use reliable method of contraception (if sexually active) from screening up to study drug discontinuation plus 180 days.

Exclusion Criteria:

  • Patients with a high risk for thrombocytopenia or hemorrhage or renal diseases: Urine protein, platelet count and coagulation tests will be done prior to intrathecal injection with SPINRAZA®
  • Patients with high risk of hydrocephalus
  • Adult patients under guardianship
  • Pregnant and/or breastfeeding females
  • Subject has received any investigational therapy or pharmacological treatment for SMA one month prior the beginning of the study
  • Subject has received gene therapy for SMA

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): NCT04159987


Contacts
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Contact: Sabrina SACCONI 0492035757 ext +33 sacconi.s@chu-nice.fr

Locations
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France
CHU de Lyon Recruiting
Lyon, Auvergne Rhone Alpes, France, 69677
Contact: Emilien Bernard    0472119065 ext +33    emilien.bernard@chu-lyon.fr   
Principal Investigator: Emilien Bernard         
Sub-Investigator: Francoise Bouhour         
Sub-Investigator: Antoine Pegat         
CHRU de Lille Recruiting
Lille, Hauts De France, France, 59000
Contact: Céline Tard    0320444145 ext +33    celine.tard@chru-lille.fr   
Principal Investigator: Céline Tard         
Sub-Investigator: Jean-Baptiste Davion         
APHP Recruiting
Paris, Ile De France, France, 94000
Contact: Edoardo Malfatti    0636963117 ext +33    edoardo.malfatti@aphp.fr   
Principal Investigator: Edoardo Malfatti         
CHU de Montpellier Recruiting
Montpellier, Occitanie, France, 34090
Contact: Elisa DE LA CRUZ       e-delacruz@chu-montpellier.fr   
Principal Investigator: Elisa DE LA CRUZ         
CHU de Toulouse Recruiting
Toulouse, Occitanie, France, 31059
Contact: Pascal Cintas    0561779440    cintas.p@chu-toulouse.fr   
Principal Investigator: Pascal Cintas         
Sub-Investigator: Blandine Acket         
Hopital de la Timone - APHM Recruiting
Marseille, Provence Alpes Cote d'Azur, France, 13005
Contact: Shahram ATTARIAN    0491386579 ext +33    shahram.attarian@ap-hm.fr   
Principal Investigator: Shahram ATTARIAN         
CHU de Nice Recruiting
Nice, Provence Alpes Cote d'Azur, France, 06000
Contact: Sabrina SACCONI    0492035757 ext +33    sacconi.s@chu-nice.fr   
Principal Investigator: Sabrina SACCONI         
Sub-Investigator: Luisa VILLA         
Sub-Investigator: Angela PUMA         
Sponsors and Collaborators
Centre Hospitalier Universitaire de Nice
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Responsible Party: Centre Hospitalier Universitaire de Nice
ClinicalTrials.gov Identifier: NCT04159987    
Other Study ID Numbers: 19-PP-09
First Posted: November 12, 2019    Key Record Dates
Last Update Posted: July 5, 2022
Last Verified: July 2022

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Motor Neuron Disease
Muscular Atrophy
Muscular Atrophy, Spinal
Atrophy
Pathological Conditions, Anatomical
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Spinal Cord Diseases
Central Nervous System Diseases
Neurodegenerative Diseases
Neuromuscular Diseases