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

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ClinicalTrials.gov Identifier: NCT01645787
Recruitment Status : Completed
First Posted : July 20, 2012
Last Update Posted : May 18, 2016
Sponsor:
Information provided by (Responsible Party):
Claudia Chiriboga, Columbia University

Tracking Information
First Submitted Date  ICMJE July 5, 2012
First Posted Date  ICMJE July 20, 2012
Last Update Posted Date May 18, 2016
Study Start Date  ICMJE June 2012
Actual Primary Completion Date September 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 19, 2012)
Six Minute Walk Test (6MWT) with Kinematic Evaluation of Gait [ Time Frame: Up to 21 Weeks ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01645787 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 19, 2012)
  • Hammersmith Functional Motor Scale, Expanded (HFMSE) [ Time Frame: Up to 21 Weeks ]
    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 ]
    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 ]
    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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Short and Long Term Treatment With 4-AP in Ambulatory SMA Patients
Official Title  ICMJE Columbia SMA Project: 4-AP as a Potential SMA Therapeutic Agent and Biological Mechanisms of Action
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Spinal Muscular Atrophy
Intervention  ICMJE
  • Drug: 4-aminopyridine
    10 mg/twice daily
    Other Names:
    • dalfampridine-ER
    • Ampyra
  • Drug: Placebo
    Crossover study involving one trial with sugar pill (placebo)
    Other Name: Sugar pill
Study Arms  ICMJE
  • Active Comparator: 4-aminopyridine (Ampyra)
    10 mg tab/ 1 tab twice daily
    Intervention: Drug: 4-aminopyridine
  • Placebo Comparator: Sugar pill
    Placebo 1 tab /twice daily
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 17, 2016)
11
Original Estimated Enrollment  ICMJE
 (submitted: July 19, 2012)
10
Actual Study Completion Date  ICMJE September 2015
Actual Primary Completion Date September 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 50 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01645787
Other Study ID Numbers  ICMJE AAAI7400
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Responsible Party Claudia Chiriboga, Columbia University
Study Sponsor  ICMJE Columbia University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Claudia A. Chiriboga, MD, MPH Columbia University
PRS Account Columbia University
Verification Date May 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP