Clinical trial NCT01645787: Short and Long Term Treatment With 4-AP in Ambulatory SMA Patients
Official title: Columbia SMA Project: 4-AP as a Potential SMA Therapeutic Agent and Biological Mechanisms of Action
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Spinal Muscular Atrophy
Keywords: Spinal Muscular Atrophy
4-aminopyridine
dalfampridine
Ampyra
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
First posted: 2012-07-20
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess whether 4-AP (Dalfampridine-ER, Ampyra) improves walking ability and endurance in adult patients with Spinal muscular atrophy (SMA) Type 3 compared to placebo and whether the duration of treatment affects outcome.

Detailed description: Spinal muscular atrophy (SMA) is a genetically determined neuromuscular disorder that results in muscle weakness and impaired functional mobility. Fatigue is a common symptom in SMA with a resultant impact on physical function and quality of life however the precise mechanisms are unknown. At present there is no treatment for SMA. There is evidence that 4-AP improves function in SMA animal models. In patients with multiple sclerosis, 4-AP was found to improve walking ability and diminish fatigue. The purpose of the study is to determine whether treatment with 4-AP is associated with an increase in walking speed and endurance compared to placebo and whether the duration of treatment affects outcome. The study comprises a short term treatment trial in which participants are treated for 2 weeks with 4-AP and placebo in random sequence followed by a long treatment trial of 6 weeks in which patients are also treated with placebo and 4 AP. The primary outcome measure of the clinical study will be the six minute walk test (6MWT), which has been documented to be a valid and sensitive instrument to identify fatigue among ambulatory SMA patients. We will also assess the effect of 4-AP on muscle and nerve electrical function via electromyography (EMG) during the short term trial. Results of this study may provide support for larger clinical trials.

Eligibility criteria: Inclusion Criteria:

1. Aged 18 to 50 years at the time of enrollment
2. Have genetically confirmed SMA 3 (homozygous absence of SMN1 exon 7)
3. Ability to walk at least 25 meters without assistance
4. Be free of major orthopedic deformities (i.e. scoliosis, contractures)
5. Normal Cystatin C clearance (\> 80 ml/min)

Exclusion Criteria:

1. Patients with a history of seizures
2. Patients with any renal impairment
3. Inability to comply with the study procedures
4. Unstable medical illness
5. Any ventilatory assistance
6. Taking experimental medication for SMA other than under this protocol
7. Pregnancy or lactation
8. Menstruating women, not sterilized or not using effective birth control
9. Planning to undergo scoliosis surgery within the next 10 months
10. Inability to give informed consent

Primary outcomes:
measure: Six Minute Walk Test (6MWT) With Kinematic Evaluation of Gait (Short Term)
timeFrame: Day 14 of each short-term intervention period
measure: Six Minute Walk Test (6MWT) With Kinematic Evaluation of Gait (Long Term)
timeFrame: Day 42 of each long-term intervention period
Secondary outcomes:
measure: Hammersmith Functional Motor Scale, Expanded (HFMSE) (Short Term)
timeFrame: Day 14 of each short-term intervention period
measure: Hammersmith Functional Motor Scale, Expanded (HFMSE) (Long Term)
timeFrame: Day 42 of each long-term intervention period
measure: Manual Muscle Testing (MMT) Total Score (Short Term)
timeFrame: Day 14 of each short-term intervention period
measure: Manual Muscle Testing (MMT) Total Score (Long Term)
timeFrame: Day 42 of each long-term intervention period
measure: Motor Unit Number Estimation (MUNE)
timeFrame: Day 14 of each short-term intervention period
Other outcomes:
Locations:
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
Study officials:
affiliation: Columbia University
name: Claudia A. Chiriboga, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: