Spinal Muscular AtrophyPhase 2/3NCT01645787
Short and Long Term Treatment With 4-AP in Ambulatory SMA Patients
A Phase 2/3 study testing 4-aminopyridine in people with Spinal Muscular Atrophy, run by Columbia University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Spinal Muscular Atrophy
- What is being tested?
- 4-aminopyridine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jun 2012to Sep 2015
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Aged 18 to 50 years at the time of enrollment
- Have genetically confirmed SMA 3 (homozygous absence of SMN1 exon 7)
- Ability to walk at least 25 meters without assistance
- Be free of major orthopedic deformities (i.e. scoliosis, contractures)
- Normal Cystatin C clearance (> 80 ml/min)
Who cannot join
- Patients with a history of seizures
- Patients with any renal impairment
- Inability to comply with the study procedures
- Unstable medical illness
- Any ventilatory assistance
- Taking experimental medication for SMA other than under this protocol
Show all 10Show fewer
- Pregnancy or lactation
- Menstruating women, not sterilized or not using effective birth control
- Planning to undergo scoliosis surgery within the next 10 months
- Inability to give informed consent
Trial locations and contacts
1 site in 1 country.
United States1 site
Columbia University Medical Center
New York, New York, 10032
About this study
Official title: Columbia SMA Project: 4-AP as a Potential SMA Therapeutic Agent and Biological Mechanisms of Action
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.
Read the 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.
- Conditions
- Spinal Muscular Atrophy
- Being tested
- 4-aminopyridine, Placebo
- Keywords
- Spinal Muscular Atrophy, 4-aminopyridine, dalfampridine, Ampyra
- Medical subject headings
- Muscular Atrophy, Spinal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
4-aminopyridineDrug
Also called dalfampridine-ER, Ampyra
10 mg/twice daily
PlaceboDrug
Also called Sugar pill
Crossover study involving one trial with sugar pill (placebo)
| Study group | Role | What they receive |
|---|---|---|
| 4-aminopyridine (Ampyra) | Active comparator | 10 mg tab/ 1 tab twice daily Receives: Drug: 4-aminopyridine |
| Sugar pill | Placebo comparator | Placebo 1 tab /twice daily Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Six Minute Walk Test (6MWT) With Kinematic Evaluation of Gait (Short Term)
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.
Measured: Day 14 of each short-term intervention period
Six Minute Walk Test (6MWT) With Kinematic Evaluation of Gait (Long Term)
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.
Measured: Day 42 of each long-term intervention period
Secondary outcomes (5)
Hammersmith Functional Motor Scale, Expanded (HFMSE) (Short Term)
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. The score range is 0 (all items failed) to 66 (all items achieved unaided), with higher score indicating higher level of motor function.
Measured: Day 14 of each short-term intervention period
Hammersmith Functional Motor Scale, Expanded (HFMSE) (Long Term)
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. The score range is 0 (all items failed) to 66 (all items achieved unaided), with higher score indicating higher level of motor function.
Measured: Day 42 of each long-term intervention period
Manual Muscle Testing (MMT) Total Score (Short Term)
MMT will involve pushing and pulling against the evaluators hand (MMT). The purpose of this test is to measure the strength in different muscles. MMT was performed on 28 muscle groups (8 muscle groups on each leg and 6 muscle groups on each arm), including proximal and distal musculature. The score range for each muscle group is 0 to 10, with a higher score indicating better muscle strength. The total score range is 0 to 280.
Measured: Day 14 of each short-term intervention period
Manual Muscle Testing (MMT) Total Score (Long Term)
MMT will involve pushing and pulling against the evaluators hand (MMT). The purpose of this test is to measure the strength in different muscles. MMT was performed on 28 muscle groups (8 muscle groups on each leg and 6 muscle groups on each arm), including proximal and distal musculature. The score range for each muscle group is 0 to 10, with a higher score indicating better muscle strength. The total score range is 0 to 280.
Measured: Day 42 of each long-term intervention period
Motor Unit Number Estimation (MUNE)
Motor Unit Number Estimation (MUNE) is a noninvasive test that identifies the number of 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 the right arm and leg while recording the response over a muscle innervated by each nerve. MUNE is calculated by determining the compound motor action potential (CMAP) amplitude or area under the curve of a distal muscle in response to supramaximal stimulation, and then dividing the result by the amplitude or area under the curve of a single motor unit action potential.
Measured: Day 14 of each short-term intervention period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jul 2012 (estimated)
- Study start1 Jun 2012
- Primary completionSep 2015
- Study completionSep 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Spinal Muscular AtrophyStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Collaborators
- United States Department of Defense
- Responsible party
- Principal investigator, Claudia Chiriboga, Columbia University
- Investigators
- Claudia A. Chiriboga, MD, MPH, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01645787
- Sponsor's protocol ID
- AAAI7400
- Status last verified
- Aug 2024
- First submitted
- 5 Jul 2012
- Last updated
- 3 Sep 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 3 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Columbia SMA Project: 4-AP as a Potential SMA Therapeutic Agent and Biological Mechanisms of Action
- ClinicalTrials.gov ID
- NCT01645787
- Acronym / sponsor ID
- AAAI7400
- Conditions
- Spinal Muscular Atrophy
- Keywords
- Spinal Muscular Atrophy, 4-aminopyridine, dalfampridine, Ampyra
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Collaborators
- United States Department of Defense
- Study start
- 1 Jun 2012 (actual)
- Primary completion
- Sep 2015 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 20 Jul 2012 (estimated)
- Results
- Posted 3 Sep 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 4-aminopyridine (Ampyra) | Active comparator | Drug: 4-aminopyridine10 mg tab/ 1 tab twice daily |
| Sugar pill | Placebo comparator | Drug: PlaceboPlacebo 1 tab /twice daily |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Aged 18 to 50 years at the time of enrollment
- Have genetically confirmed SMA 3 (homozygous absence of SMN1 exon 7)
- Ability to walk at least 25 meters without assistance
- Be free of major orthopedic deformities (i.e. scoliosis, contractures)
- Normal Cystatin C clearance (> 80 ml/min)
Key exclusion criteria (10 listed)
- Patients with a history of seizures
- Patients with any renal impairment
- Inability to comply with the study procedures
- Unstable medical illness
- Any ventilatory assistance
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 4-aminopyridineAlso: dalfampridine-ER, Ampyra10 mg/twice daily | Drug | 4-aminopyridine (Ampyra) |
| PlaceboAlso: Sugar pillCrossover study involving one trial with sugar pill (placebo) | Drug | Sugar pill |
Primary outcome
Six Minute Walk Test (6MWT) With Kinematic Evaluation of Gait (Short Term)
Time frame: Day 14 of each short-term intervention period
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.
Six Minute Walk Test (6MWT) With Kinematic Evaluation of Gait (Long Term)
Time frame: Day 42 of each long-term intervention period
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.
5 secondary outcomes
Hammersmith Functional Motor Scale, Expanded (HFMSE) (Short Term)
Time frame: Day 14 of each short-term intervention period
Hammersmith Functional Motor Scale, Expanded (HFMSE) (Long Term)
Time frame: Day 42 of each long-term intervention period
Manual Muscle Testing (MMT) Total Score (Short Term)
Time frame: Day 14 of each short-term intervention period
Manual Muscle Testing (MMT) Total Score (Long Term)
Time frame: Day 42 of each long-term intervention period
Motor Unit Number Estimation (MUNE)
Time frame: Day 14 of each short-term intervention period
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Sep 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Claudia A. Chiriboga, MD, MPH principal investigator
Columbia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing 4-aminopyridine in people with Spinal Muscular Atrophy, run by Columbia University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Six Minute Walk Test (6MWT) With Kinematic Evaluation of Gait (Short Term) (time frame: Day 14 of each short-term intervention period). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Sep 2024.