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

NCT01645787 | Completed Phase 2 Results FDA Drug

• 1 other identifier: AAAI7400
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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.

Conditions

Spinal Muscular Atrophy

Keywords

Spinal Muscular Atrophy; 4-aminopyridine; dalfampridine; Ampyra

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Day 42 of each long-term intervention period

Secondary Outcomes (5)

• Hammersmith Functional Motor Scale, Expanded (HFMSE) (Short Term)

  Day 14 of each short-term intervention period

• Hammersmith Functional Motor Scale, Expanded (HFMSE) (Long Term)

  Day 42 of each long-term intervention period

• Manual Muscle Testing (MMT) Total Score (Short Term)

  Day 14 of each short-term intervention period

• Manual Muscle Testing (MMT) Total Score (Long Term)

  Day 42 of each long-term intervention period

• Motor Unit Number Estimation (MUNE)

  Day 14 of each short-term intervention period

Study Arms (2)

4-aminopyridine (Ampyra)

ACTIVE COMPARATOR

10 mg tab/ 1 tab twice daily

Drug: 4-aminopyridine

Sugar pill

PLACEBO COMPARATOR

Placebo 1 tab /twice daily

Drug: Placebo

Interventions

4-aminopyridine DRUG

10 mg/twice daily

Also known as: dalfampridine-ER, Ampyra

4-aminopyridine (Ampyra)

Placebo DRUG

Crossover study involving one trial with sugar pill (placebo)

Also known as: Sugar pill

Sugar pill

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Columbia University: lead
• United States Department of Defense: collaborator

Study Sites (1)

Columbia University Medical Center

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Muscular Atrophy, Spinal

Interventions

4-Aminopyridine; Sugars

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; Neuromuscular Diseases

Intervention Hierarchy (Ancestors)

Aminopyridines; Amines; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carbohydrates

Results Point of Contact

• Title: Claudia A. Chiriboga, MD, MPH
• Organization: Columbia University

cac3@columbia.edu

(212) 305-8549

Study Officials

• Claudia A. Chiriboga, MD, MPH

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Neurology and Pediatrics at CUMC

Study Record Dates

• First Submitted: July 5, 2012
• First Posted: July 20, 2012
• Study Start: June 1, 2012
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2015
• Last Updated: September 3, 2024
• Results First Posted: September 3, 2024

Record last verified: 2024-08

Locations

US (1)