NCT01645787

Columbia SMA Project: 4-AP as a Potential SMA Therapeutic Agent and Biological Mechanisms of Action

Completed Phase 2/Phase 3 Results posted Last updated 6 August 2024

What this trial tests

Phase 2/Phase 3 trial testing 4-aminopyridine in Spinal Muscular Atrophy in 11 participants. Completed in 1 September 2015.

Timeline

1 June 2012

Primary endpoint
1 September 2015

1 September 2015

Quick facts

Lead sponsor	Columbia University
Phase	Phase 2/Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	triple
Primary purpose	treatment
Enrollment	11
Start date	1 June 2012
Primary completion	1 September 2015
Estimated completion	1 September 2015
Sites	1 location across United States

Drugs / interventions tested

• 4-aminopyridine — full drug profile →
• Placebo

Conditions studied

• Spinal Muscular Atrophy — all drugs for Spinal Muscular Atrophy →

Sponsor

Columbia University

Who can join

Adults 18 to 50, any sex, with Spinal Muscular Atrophy. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• 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
• 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

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Spinal muscular atrophy: From approved therapies to future therapeutic targets for personalized medicine.
   Chaytow H, Faller KME, Huang YT, Gillingwater TH. · · 2021 · cited 103× · PMID 34337562 · DOI 10.1016/j.xcrm.2021.100346
2. Therapy development for spinal muscular atrophy: perspectives for muscular dystrophies and neurodegenerative disorders.
   Jablonka S, Hennlein L, Sendtner M. · · 2022 · cited 37× · PMID 34983696 · DOI 10.1186/s42466-021-00162-9
3. Drug treatment for spinal muscular atrophy types II and III.
   Wadman RI, van der Pol WL, Bosboom WM, Asselman FL, et al · · 2020 · cited 32× · PMID 32006461 · DOI 10.1002/14651858.cd006282.pub5
4. In Search of a Cure: The Development of Therapeutics to Alter the Progression of Spinal Muscular Atrophy.
   Ojala KS, Reedich EJ, DiDonato CJ, Meriney SD. · · 2021 · cited 16× · PMID 33562482 · DOI 10.3390/brainsci11020194
5. GEMINs: potential therapeutic targets for spinal muscular atrophy?
   Borg R, Cauchi RJ. · · 2014 · cited 14× · PMID 25360080 · DOI 10.3389/fnins.2014.00325
6. Systematic Literature Review of Clinical and Economic Evidence for Spinal Muscular Atrophy.
   Yang M, Awano H, Tanaka S, Toro W, et al · · 2022 · cited 12× · PMID 35307799 · DOI 10.1007/s12325-022-02089-2
7. Developing therapies for spinal muscular atrophy.
   Wertz MH, Sahin M. · · 2016 · cited 11× · PMID 26173388 · DOI 10.1111/nyas.12813
8. Advances in Drug Discovery Targeting Lysosomal Membrane Proteins.
   Wang H, Zhu Y, Liu H, Liang T, et al · · 2023 · cited 9× · PMID 37111358 · DOI 10.3390/ph16040601