Dalfampridine + Physical Therapy for Multiple Sclerosis
(AmpPT Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
Sponsor: MGH Institute of Health Professions
Disqualifiers: Neurological disorders, Orthopedic conditions, Hypertension, Diabetes, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?The goal of this clinical trial is to evaluate if combining a medication that can help improve walking in people with multiple sclerosis (MS) with a physical therapy program is better for improving walking than either treatment alone. The main questions this study will answer are:
* Does combining dalfampridine with physical therapy improve mobility more than physical therapy without concurrent dalfampridine?
* Is the combined treatment associated with better outcomes than the medication (dalfampridine) on its own?
* How do the individual treatments (dalfampridine, physical therapy) alone compare to each other?
Participants with MS-related mobility deficits will:
* Receive 6 weeks of dalfampridine treatment to assess the effects of this treatment.
* After stopping the medication for 2 weeks, the investigators will re-evaluate walking, then randomly assign individuals to a 6-week physical therapy program.
* Half of the participants will receive physical therapy while resuming dalfampridine treatment. The other half of the participants will receive physical therapy without resuming the medication.
Researchers will compare the combination treatment group (medication plus physical therapy) to the physical therapy only group to see if the combined treatment improves walking-related function. Approximately 3 months after finishing the physical therapy program, participants will undergo a final evaluation to see if the treatment effects have been maintained.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications, but you cannot be currently taking dalfampridine or have stopped it due to side effects. You will need to stop dalfampridine for 2 weeks during the trial.
What data supports the effectiveness of the drug dalfampridine combined with physical therapy for improving mobility in people with multiple sclerosis?
Research shows that dalfampridine, when combined with physical therapy, may improve walking speed in people with multiple sclerosis more than physical therapy alone. In a small study, participants taking dalfampridine and doing physical therapy improved their walking speed by about 20.7%, compared to 10.8% for those only doing physical therapy.
12345Is the combination of Dalfampridine and Physical Therapy safe for humans?
Dalfampridine, also known as Ampyra or Fampridine, is generally well tolerated but may increase the risk of seizures, especially in people with kidney problems. Common side effects include urinary tract infections, insomnia, headache, and dizziness. It is important to avoid use in individuals with a history of seizures.
46789How does the treatment of Dalfampridine combined with physical therapy differ from other treatments for multiple sclerosis?
This treatment is unique because it combines Dalfampridine, a drug that helps improve walking by blocking potassium channels in nerve cells, with physical therapy to enhance mobility in people with multiple sclerosis. The combination aims to improve walking speed more effectively than either treatment alone.
12478Eligibility Criteria
This trial is for people with MS who can walk a bit but have trouble with mobility. They should be able to stand on their own and understand instructions, haven't had a relapse in 3 months, and aren't currently on dalfampridine or physical therapy. People with other conditions affecting movement, recent hospital stays, uncontrolled blood pressure or diabetes, history of seizures, kidney issues, or women who are pregnant can't join.Inclusion Criteria
I have been free from cancer relapse for at least 3 months.
My cognitive function is relatively good.
I am not currently on dalfampridine and have never stopped it due to side effects.
+5 more
Exclusion Criteria
Unable to follow a 3-step verbal command in English
I have a history of seizures.
Women who are breastfeeding, pregnant, or trying to become pregnant
+5 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Dalfampridine Treatment
Participants receive 6 weeks of dalfampridine treatment to assess the effects of this treatment
6 weeks
Regular visits for monitoring
Washout and Re-evaluation
Participants stop dalfampridine for 2 weeks and undergo re-evaluation of walking
2 weeks
Physical Therapy with/without Dalfampridine
Participants are randomly assigned to 6 weeks of physical therapy with or without resuming dalfampridine
6 weeks
Twice per week for physical therapy
Follow-up
Participants are monitored for safety and effectiveness after treatment
12 weeks
Final evaluation approximately 3 months after physical therapy
Participant Groups
Researchers are testing if taking the drug dalfampridine along with physical therapy helps improve walking more than just one treatment alone. Participants will first take the medication for six weeks then stop for two before starting a six-week physical therapy program where half will also resume the medication.
3Treatment groups
Active Control
Group I: Physical therapyActive Control1 Intervention
One-on-one outpatient physical therapy twice per week
Group II: Dalfampridine onlyActive Control1 Intervention
10 mg tablet twice per day
Group III: Dalfampridine plus physical therapyActive Control1 Intervention
10 mg tablet twice per day while receiving one-on-one outpatient physical therapy twice per week
Dalfampridine is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Ampyra for:
- Improvement of walking in adults with multiple sclerosis
🇪🇺 Approved in European Union as Fampyra for:
- Improvement of walking in adults with multiple sclerosis
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
MGH Institute of Health ProfessionsBoston, MA
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Who Is Running the Clinical Trial?
MGH Institute of Health ProfessionsLead Sponsor
References
Dalfampridine for Mobility Limitations in People With Multiple Sclerosis May Be Augmented by Physical Therapy: A Non-randomized Two-Group Proof-of-Concept Pilot Study. [2022]Purpose: To demonstrate proof-of-concept for a combined physical therapy and pharmacological intervention and obtain preliminary estimates of the therapeutic efficacy of a motor-relearning physical therapy intervention with and without concurrent dalfampridine treatment on gait speed in people with mobility limitations due to multiple sclerosis (MS). Methods: Using a non-randomized, two-group design, 4 individuals with MS newly prescribed dalfampridine as part of their routine medical care, and 4 individuals with MS not taking dalfampridine completed a 3-week drug run-in or no-treatment baseline, respectively. After 3 weeks, all participants commenced physical therapy twice weekly for 6 weeks. Participants taking dalfampridine took the medication for the study duration. The physical therapy program comprised functional strengthening, gait training, balance training, and dual-task training. The primary outcome was Timed 25-foot Walk (T25FW) at the end of the 6-week physical therapy program. Results: For the 4 participants taking dalfampridine, average improvement in T25FW on drug only was 12.8% (95% CI 1.2 to 24.4%). During the 6-week physical therapy phase, both groups significantly improved T25FW, but the effect tended to favor the group taking dalfampridine (mean difference = -0.93 s, 95% CI -1.9 to 0.07 s, p = 0.064, d = 1.6). Whereas the physical therapy group had average T25FW improvement of 10.8% (95% CI 1.0 to 20.5%), the physical therapy plus dalfampridine group demonstrated average improvement of 20.7% (95% CI 3.8 to 37.6%). Conclusions: Further research is warranted to examine whether dalfampridine for mobility impairment may be augmented by physical therapy in people with MS.
Long-term effects of dalfampridine in patients with multiple sclerosis. [2022]Dalfampridine is the extended-release formulation of 4-aminopyridine and is approved for the symptomatic treatment of impaired mobility in patients with multiple sclerosis. Our aim was to examine the short- and long-term effects of treatment with dalfampridine on motoric and cognitive assessment parameters of multiple sclerosis (MS) patients over 9-12 months.
Assessing dalfampridine efficacy in the physician's office. [2013]Dalfampridine (extended release 4-aminopyridine) is shown in three recent randomised controlled trials to improve walking speed in people with multiple sclerosis; however, the trial literature makes it clear that dalfampridine is effective in only a subset of patients. For the neurologist working in an everyday physician's office, a key question arises: How to distinguish the few who experience a meaningful clinical benefit, from the many who do not? This question has not yet been adequately addressed in the available literature.
Development of dalfampridine, a novel pharmacologic approach for treating walking impairment in multiple sclerosis. [2014]Walking impairment is a clinical hallmark of multiple sclerosis (MS). Dalfampridine-ER, an extended-release formulation of dalfampridine (also known by its chemical name, 4-aminopyridine, and its international nonproprietary name, fampridine), was developed to maintain drug plasma levels within a narrow therapeutic window, and assessed for its ability to improve walking in MS. The putative mechanism of action of dalfampridine-ER is restoration of axonal conduction via blockade of the potassium channels that become exposed during axonal demyelination. Two pivotal phase III clinical trials demonstrated that dalfampridine-ER 10-mg tablets administered twice daily improved walking speed and patient-reported perceptions of walking in some patients. Dalfampridine-ER was generally well tolerated, and, at the approved dose, risk of seizure was neither elevated relative to placebo nor higher than the rate in the MS population. Dalfampridine-ER (AMPYRA®) was approved in the United States for the treatment of walking in patients with MS as demonstrated by an increase in walking speed. The use of the dalfampridine-ER is contraindicated in patients with a history of seizure. It is the first pharmacologic therapy for this indication and has been incorporated into clinical management of MS.
A phase 3 trial of extended release oral dalfampridine in multiple sclerosis. [2022]A previous phase 3 study showed significant improvement in walking ability in multiple sclerosis (MS) patients treated with oral, extended-release dalfampridine (4-aminopyridine) 10mg twice daily. The current study was designed to confirm efficacy and further define safety and pharmacodynamics.
Dalfampridine prior authorization program: a cohort study. [2023]Dalfampridine (Ampyra) is indicated to improve walking in patients with multiple sclerosis (MS) and was found to be effective in 35%-43% of individuals with MS in clinical trials. Dalfampridine may increase seizure risk, particularly in patients with renal impairment. A U.S. managed care expert consensus panel agreed that patient access to dalfampridine is best managed by a prior authorization (PA) in accordance with the FDA-approved labeling. To ensure safe and appropriate dalfampridine use, a health plan developed and implemented a 2-phase point-of-sale PA program.
Sustained-release oral fampridine in multiple sclerosis: a randomised, double-blind, controlled trial. [2022]Clinical studies suggested that fampridine (4-aminopyridine) improves motor function in people with multiple sclerosis. This phase III study assessed efficacy and safety of oral, sustained-release fampridine in people with ambulatory deficits due to multiple sclerosis.
Dalfampridine in multiple sclerosis. [2017]Dalfampridine (4-aminopyridine or 4-AP) is a potassium channel blocker that is historically known in the literature as fampridine (INN). This review begins with an outline of the pharmacology and pharmacokinetics. Early clinical trials are highlighted, followed by a review of the more recent phase II and III placebo-controlled clinical trials that have examined dalfampridine in multiple sclerosis patients. In these trials, extended-release dalfampridine was shown to result in an average 25% increase in the walking speed in more than one-third of the patients who received the drug and met the prescribed criteria for consistent responders. The safety profile of dalfampridine is also reviewed, with a focus on the risk for epileptic seizures as an adverse effect.
Extended-release dalfampridine in the management of multiple-sclerosis-related walking impairment. [2021]Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system that causes neurological impairment in young adults. As part of the disease, ambulation remains one of the most disabling features of multiple sclerosis. Extended-release dalfampridine is a long-acting form of 4-aminopyridine that has been shown in two phase III trials to increase ambulation speed in a subset of patients with multiple sclerosis (timed walk responders). The primary endpoint of these studies was 'responder status', analyzing difference in the proportion of timed walk responders between extended-release dalfampridine and placebo groups. Extended-release dalfampridine exerts its effects by inhibiting voltage-activated K(+) channels and has been previously demonstrated to improve action potential propagation in demyelinated nerve fibers in vitro. Side effects of extended-release dalfampridine include increased urinary tract infections, insomnia, headache, asthenia, dizziness, back pain, and paresthesias. Rare seizure events are also reported on the approved dose of 10 mg every 12 h. In this review we will summarize the results of key phase II and phase III trials of extended-release dalfampridine, its safety, and potential use in patients with multiple sclerosis.