Adults With SMA Treated With Nusinersen

Study Overview
=================
Brief Summary
-----------------
This is a single center, 22-month observational study of nusinersen treatment in adult patients with spinal muscular atrophy (SMA). There will be a total of seven visits. Nusinersen is provided as standard of care and not considered research in this study. Information will be collected regarding the general health, and function including muscle strength of, as well as any positive and/or adverse events experienced by the study participants.

Detailed Description
-----------------
This is a single center, 22-month observational study of nusinersen treatment in adult patients with SMA. There will be a total of five visits. All subjects will be evaluated at a screening visit no more than four weeks before starting their standard of care nusinersen treatment to determine their eligibility for participation. Eligible patients will complete their standard induction intrathecal nusinersen treatment on day 1, 15, 29 and 60 followed by maintenance doses every four months. Subjects will be reevaluated after completing the loading doses at 2 months followed by every four-month evaluations for the total duration of the treatment of 22 months. Currently, there is no data published on patients receiving this treatment over the age of 18. Without published data collected from research, it is difficult for adult patients to get approval from their insurance companies to receive this treatment. This study hopes to collect data, in order to make this treatment option easier for patients with SMA to access and in general learn how well nusinersen is working in adult patients with SMA overtime.

Official Title
-----------------
Characterizing Longitudinal Outcomes in Adults With SMA Treated With Nusinersen

Conditions
-----------------
Spinal Muscular Atrophy

Intervention / Treatment
-----------------
* Drug: nusinersen


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 18 to 60 years Genetic confirmation of 5q SMA documented by the homozygous deletion of both SMN1 genes on standard genetic tests for the disorder SMN2 copy number of 3 or greater Subjects must be able to walk thirty feet without assistance (i.e. no canes, walkers) Interest in participating and the ability to meet the study requirements Women of childbearing-age are required to be on birth control or abstain while participating in the research study Exclusion Criteria: Subjects with history of spinal disease that will interfere with the lumbar puncture procedure Subjects with history of bacterial meningitis or encephalitis Subjects with history of use of investigational drug treatment for SMA in the last six months, or plan on enrolling in any other treatment trial during the duration of this trial History of treatment with gene therapy, stem cell or antisense oligonucleotide Patients with co-morbid conditions that preclude travel, testing or study medications Patients who are, in the investigator's opinion, mentally or legally incapacitated from providing informed consent for the study, or are otherwise unable to meet study requirements or cooperate reliably with study procedures, especially strength testing Women who are pregnant or who intend to become pregnant while participating in the research study or who are breastfeeding

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| SMA nusinersen adult cohort<br>The nusinersen treatment will be given as standard of care. The treatment (which is NOT research, but the standard care) will be given by an injection into the cerebrospinal fluid (fluid in your spine) through a needle inserted into your lower back. Participants will receive a 12 mg (5 mL) dose during each administration/injection, which will occur on the following days: 1 (baseline), 15, 29, and 60. Following the 60 day treatment, participants will receive treatment every 4 months (6, 10, 14 etc.). After the 60 day, 6 month, 10 month, 14 month, 18 month and 22 month treatments the study team will see each participant afterwards to collect information to evaluate your general health, function and response to the treatment for the study. | Drug: nusinersen<br>* SPINRAZA (nusinersen) is FDA approved to treat spinal muscular atrophy (SMA) through intrathecal injection.<br>* Other names: SPINRAZA;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscle strength | To evaluate the effect of nusinersen treatment on muscle strength in ambulatory SMA adults | 22 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Six Minute Walk Test | 6 Minute Walk Test (6WMT) | 22 months | 
| Change in Hammersmith Functional Motor Scale Expanded | Hammersmith Functional Motor Scale Expanded (HFMSE) | 22 months | 
| Change in SMA Functional Rating Scale | modified SMA Functional Rating Scale(SMA-FRS) | 22 months | 
| Change in Forced Vital Capacity | Forced Vital Capacity (FVC) | 22 months | 
| Change in Negative Inspiratory Force | Negative Inspiratory Force (NIF) | 22 months | 
| Change in lean muscle mass | Muscle mass measured using Dual-Energy X-Ray Absorptiometry (DXA) | 22 months | 
| Change in Quality of Life | Quality of life will be measured using 36-Item Short Form Survey (SF-36) | 22 months | 
| Change in Ulnar and Peroneal muscle measures | Compound Muscle Action Potential Amplitude (CMAP) will be recorded | 22 months | 
| Change in Motor Unit Number Estimation (MUNE) | Ulnar nerve (Recording at the Abductor Digiti Minimi muscle) MUNE scores will be recorded | 22 months | 
| Number of participants that experience Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of participants who experience adverse outcomes | 22 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
nusinersen, Spinraza