Clinical Study of Spinal Muscular Atrophy

The investigators propose to prepare for clinical trials where SMA patients are asked to join the research effort. The visits will include questions, physical exam, blood drawing, and sometimes X-rays and a skin biopsy. The investigators will use modern computer methods to process the information during which the investigators will plan a clinical trial. Once the clinical trial begins, the investigators will offer SMA patients participation if they meet the criteria for that trial.

Identifying an effective SMA treatment is very important because there is currently none. Clinical trials are the only way to decide whether a new treatment works in SMA patients or not.

Study Overview

• Status: Completed
• Conditions: Spinal Muscular Atrophy

Detailed Description

Spinal Muscular Atrophy (SMA) is one of the most devastating neurological diseases of childhood. Affected infants and children suffer from progressive muscle weakness caused by degeneration of lower motor neurons in the spinal cord and brainstem. Clinically, four phenotypes are distinguished within the continuous spectrum of disease severity based on the age of onset and the highest motor milestone ever achieved. SMA is caused by homozygous deletion of the survival motor neuron-1 (SMN1) gene. A related gene, SMN2, produces low levels of full-length SMN protein due to inefficient splicing. There is an inverse correlation between SMN copy number and disease severity, presumably mediated by levels of full length SMN protein. Therefore, increasing the amount of full-length SMN protein is a promising treatment strategy. Several drugs targeting splicing efficiency have resulted in increased SMN protein in preclinical assays and are now awaiting clinical testing.

With the future objective to conduct clinical trials in SMA, the proposed project has 3 specific aims: 1) To establish a web-based database that will serve to enroll the patient population and that will facilitate timely recruitment for future clinical trials; (2) to plan for clinical trials by a) developing reliable outcome measures, and (b) establishing the infrastructure needed to carry out efficient clinical trials, (c) convening meetings of preclinical and clinical researchers involved in SMA drug development to select candidate drugs, and (3) to characterize the patient population from a clinical and molecular point of view.

• Study Type: Observational
• Enrollment (Actual): 120

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University SMA Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

People diagnosed with Spinal Muscular Atrophy types I, II, or III before the age of 17.

Description

Inclusion Criteria

• Clinical diagnosis of Spinal Muscular Atrophy
• Genetic diagnosis of SMN gene deletion
• Parents or if applicable subjects must give informed consent
• must be capable of complying with the study procedures
• Female subjects of child-bearing potential must agree to undergo pregnancy test prior to radiological studies
• Diagnosis of SMA before age 19 years

Exclusion Criteria:

• Unstable medical condition precluding participation
• Significant respiratory compromise that would interfere with safe travel to site of evaluation. (The clinical site PI decides when air travel is not recommended and when the patient's location is not within a reasonably safe driving distance (upper limit 150-250 miles)

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hammersmith Functional Motor Scale Expanded (HFMSE)	For SMAII/III patients over 2 years of age, we will additionally administer the Hammersmith SMA functional motor scale (H-SMA-FMS), a disease-specific instrument.	Up to 36 months
Gross Motor Function Scale (GMFM)	The GMFM contains 88 items in 5 dimensions: (A) lying and rolling, (B) sitting, (C) crawling, (D) standing, and (E) walking.	Up to 36 months

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: The Spinal Muscular Atrophy Foundation
• Investigators: Principal Investigator: Darryl C De Vivo, MD, Columbia University

Study record dates

Study Major Dates

• Study Start: May 1, 2005
• Primary Completion (Actual): August 17, 2011
• Study Completion (Actual): August 17, 2011

Study Registration Dates

• First Submitted: March 1, 2007
• First Submitted That Met QC Criteria: March 1, 2007
• First Posted (Estimate): March 5, 2007

Study Record Updates

• Last Update Posted (Actual): March 21, 2023
• Last Update Submitted That Met QC Criteria: March 20, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: pediatric; neuromuscular disease
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neuromuscular Diseases; Neurodegenerative Diseases; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Spinal Cord Diseases; Motor Neuron Disease; Muscular Atrophy; Atrophy; Muscular Atrophy, Spinal
• Other Study ID Numbers: AAAB1635; CU52029001 (Other Identifier: SMA)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO