Short and Long Term Treatment With 4-AP in Ambulatory SMA Patients

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Claudia Chiriboga, Columbia University
ClinicalTrials.gov Identifier:
NCT01645787
First received: July 5, 2012
Last updated: February 2, 2015
Last verified: February 2015
  Purpose

The purpose of this study is to assess whether 4-AP (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.


Condition Intervention Phase
Spinal Muscular Atrophy
Drug: 4-aminopyridine
Drug: Placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Columbia SMA Project: 4-AP as a Potential SMA Therapeutic Agent and Biological Mechanisms of Action

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • Six Minute Walk Test (6MWT) with Kinematic Evaluation of Gait [ Time Frame: Up to 21 Weeks ] [ Designated as safety issue: No ]
    The primary outcome measure will be distance walked in the 6MWT. This measure is an objective evaluation of functional capacity which measures the distance a person can walk quickly in six minutes and is most representative of a person's ability because the test intensity is self-selected. The 6MWT can be safely performed in ambulatory SMA patients and correlates with standard SMA outcome measures including timed walking tests. In SMA, the 6MWT may be more sensitive to clinically meaningful changes in patients with type 3 SMA as it is a direct measure of their functional mobility.


Secondary Outcome Measures:
  • Hammersmith Functional Motor Scale, Expanded (HFMSE) [ Time Frame: Up to 21 Weeks ] [ Designated as safety issue: No ]
    Assessments of motor function are clinically relevant and are a good adjunct to tests of walking ability. The HFMSE, a 33-item scale designed for SMA type 2 and 3 patients, and is associated with minimal patient burden requiring only standard equipment and is completed on average in less than 15 minutes. The HFMSE showed good test-retest reliability and is correlated with other clinical and physiological measures in SMA.

  • Manual Muscle Testing (MMT)/Hand Held Dynamometer (HHD) [ Time Frame: Up to 21 Weeks ] [ Designated as safety issue: No ]
    MMT will involve pushing and pulling against the evaluators hand (MMT) and HHD will involve pushing or pulling as against a handheld measuring device. The purpose of these tests is to measure the strength in different muscles. The MMT involves testing fourteen muscle groups of the arm and leg on both sides of the body. The evaluator will alternate sides between tests. The measuring device will be used on 10 muscle groups on both sides of the body.

  • Change in Motor Unit Number Estimation (MUNE)/Nerve Conduction Study (NCS) [ Time Frame: Baseline, Week 2 and Week 5 ] [ Designated as safety issue: No ]
    Motor Unit Number Estimation (MUNE) is a noninvasive test that identifies the number of surviving motor units (motor nerve cells and the territory of muscle fibers they control) using electrical muscle stimulation and recording the response. The nerve conduction study involves the administration of modest electrical stimulations (pulsations or throbbing sensations from low level electricity) to a total of 4 nerves in your right arm and leg while recording the response over a muscle innervated by each nerve.


Estimated Enrollment: 12
Study Start Date: June 2012
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 4-aminopyridine (Ampyra)
10 mg/twice daily
Drug: 4-aminopyridine
10 mg/twice daily
Other Names:
  • dalfampridine
  • Ampyra
Placebo Comparator: Sugar pill
Placebo
Drug: Placebo
Crossover study involving one trial with sugar pill (placebo)
Other Name: Sugar pill

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

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01645787

Locations
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
Sponsors and Collaborators
Columbia University
Investigators
Principal Investigator: Claudia A. Chiriboga, MD, MPH Columbia University
  More Information

No publications provided

Responsible Party: Claudia Chiriboga, Associate Professor of Clinical Neurology, Columbia University
ClinicalTrials.gov Identifier: NCT01645787     History of Changes
Other Study ID Numbers: AAAI7400
Study First Received: July 5, 2012
Last Updated: February 2, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Columbia University:
Spinal Muscular Atrophy
4-aminopyridine
dalfampridine
Ampyra

Additional relevant MeSH terms:
Muscular Atrophy
Muscular Atrophy, Spinal
Atrophy
Central Nervous System Diseases
Motor Neuron Disease
Nervous System Diseases
Neurodegenerative Diseases
Neurologic Manifestations
Neuromuscular Diseases
Neuromuscular Manifestations
Pathological Conditions, Anatomical
Signs and Symptoms
Spinal Cord Diseases
4-Aminopyridine
Cardiovascular Agents
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Potassium Channel Blockers
Therapeutic Uses

ClinicalTrials.gov processed this record on May 03, 2015