Dalfampridine + Physical Therapy for Multiple Sclerosis

(AmpPT Trial)

Overseen By Prudence Plummer, PhD, PT

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: MGH Institute of Health Professions

Disqualifiers: Neurological disorders, Orthopedic conditions, Hypertension, Diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

48 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining dalfampridine with physical therapy improves walking in individuals with multiple sclerosis (MS) more effectively than either treatment alone. The researchers aim to determine if this combination leads to better mobility outcomes compared to using only the medication or only physical therapy. Individuals with MS who have difficulty walking and have been relapse-free for at least three months may qualify to participate. Participants will initially take dalfampridine, then switch to physical therapy, with some continuing the medication to compare effects. The study seeks to identify which treatment combination most effectively maintains walking improvements. As a Phase 4 trial, this research focuses on understanding how the already FDA-approved treatment benefits more patients, offering participants a chance to contribute to valuable insights.

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 is the safety track record for these treatments?

Research has shown that dalfampridine, a medication used to improve walking in people with multiple sclerosis (MS), is generally safe at a dose of 10 mg taken twice daily, though it has a narrow safety range. More than 2% of patients have reported side effects such as dizziness, headache, and nausea. A significant risk of dalfampridine is seizures, particularly if the dose is too high or not taken correctly. Despite these risks, the safety record of dalfampridine over several years aligns with findings from clinical trials.

When combined with physical therapy, no new safety concerns have emerged beyond those known for dalfampridine alone. Physical therapy is generally safe and involves exercises to enhance strength and mobility. This study aims to determine if adding physical therapy alters the benefits or risks of dalfampridine. The advanced stage of this trial suggests that dalfampridine is well-tolerated under the conditions studied. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about combining dalfampridine with physical therapy for treating multiple sclerosis (MS) because it offers a unique approach compared to existing treatments. Most current MS therapies focus on modulating the immune system to slow disease progression, but dalfampridine works differently by improving nerve signal conduction, potentially enhancing mobility. When used alongside physical therapy, which helps build strength and coordination, this combination might provide a synergistic effect, improving patients' walking ability and overall quality of life more effectively than either treatment alone. This dual approach could represent a significant advancement in addressing MS-related mobility challenges.

What evidence suggests that this trial's treatments could be effective for improving mobility in multiple sclerosis?

Research has shown that dalfampridine, one of the treatments in this trial, can help people with multiple sclerosis (MS) walk faster, improving their speed by about 25%. This medication has proven effective for many patients compared to a placebo. In this trial, some participants will receive dalfampridine alone, while others will receive physical therapy alone. Another group will receive a combination of dalfampridine and physical therapy. Studies suggest that combining dalfampridine with physical therapy does not lead to further improvements in function or quality of life beyond what each can achieve individually. ^{6 7 8 9 10}

Who Is on the Research Team?

Prudence Plummer, PhD, PT

Principal Investigator

MGH Institute of Health Professions

Are You a Good Fit for This Trial?

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.

Exclusion Criteria

Unable to follow a 3-step verbal command in English

Women who are breastfeeding, pregnant, or trying to become pregnant

I have a history of seizures.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Dalfampridine
• Physical therapy

Trial Overview 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.

How Is the Trial Designed?

Group I: Physical therapy Active Control 1 Intervention

One-on-one outpatient physical therapy twice per week

Group II: Dalfampridine only Active Control 1 Intervention

10 mg tablet twice per day

Group III: Dalfampridine plus physical therapy Active Control 1 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

Who Is Running the Clinical Trial?

MGH Institute of Health Professions

Lead Sponsor

Trials

19

Recruited

2,200+

Published Research Related to This Trial

Extended-release dalfampridine has been shown to significantly increase ambulation speed in patients with multiple sclerosis, particularly in those identified as 'timed walk responders' during two phase III trials.

While effective, extended-release dalfampridine can cause side effects such as urinary tract infections, insomnia, and rare seizure events, highlighting the need for careful monitoring in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended-release dalfampridine in the management of multiple-sclerosis-related walking impairment. Hersh, C., Rae-Grant, A.[2021]

Dalfampridine-ER is an effective treatment for improving walking speed in patients with multiple sclerosis, as shown in two pivotal phase III clinical trials, where it was administered at a dose of 10 mg twice daily.

The drug works by blocking potassium channels to restore axonal conduction and was generally well tolerated, with no increased risk of seizures compared to placebo, although it is contraindicated in patients with a history of seizures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of dalfampridine, a novel pharmacologic approach for treating walking impairment in multiple sclerosis. Blight, AR., Henney, HR., Cohen, R.[2014]

In a study involving 8 individuals with multiple sclerosis, those taking dalfampridine showed a 12.8% improvement in gait speed during a 3-week baseline period, suggesting the drug may enhance mobility.

After 6 weeks of physical therapy, participants taking dalfampridine experienced a greater average improvement in gait speed (20.7%) compared to those not on the medication (10.8%), indicating that combining dalfampridine with physical therapy may be more effective for improving mobility in MS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Plummer, P., Markovic-Plese, S., Giesser, B.[2022]

In a study of 52 multiple sclerosis patients, dalfampridine significantly improved walking ability and reduced motoric and cognitive fatigue within just 2 weeks of treatment, with these benefits lasting up to 9-12 months.

After 9-12 months, improvements in cognitive function, specifically measured by the PASAT test, were also observed, indicating that dalfampridine has both short- and long-term positive effects on mobility and cognitive performance in MS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term effects of dalfampridine in patients with multiple sclerosis. Ruck, T., Bittner, S., Simon, OJ., et al.[2022]

In a phase III trial involving 301 patients with multiple sclerosis, fampridine significantly improved walking ability, with 35% of patients showing a positive response compared to only 8% in the placebo group.

The improvement in walking speed for fampridine-treated patients was substantial at 25.2%, and this was linked to a meaningful reduction in reported ambulatory disability, indicating its efficacy as a treatment for motor function deficits in multiple sclerosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sustained-release oral fampridine in multiple sclerosis: a randomised, double-blind, controlled trial. Goodman, AD., Brown, TR., Krupp, LB., et al.[2022]

In a double-blind trial involving 239 patients with multiple sclerosis, dalfampridine (10mg twice daily) significantly improved walking ability, with 42.9% of patients showing consistent improvement compared to only 9.3% in the placebo group.

The study demonstrated that the improvement in walking speed was maintained over the dosing period, with an average increase of 24.7% during treatment and 25.7% at the last visit, indicating the drug's efficacy and safety profile remains consistent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 3 trial of extended release oral dalfampridine in multiple sclerosis. Goodman, AD., Brown, TR., Edwards, KR., et al.[2022]

Dalfampridine, a potassium channel blocker, has been shown to significantly improve walking speed by an average of 25% in over one-third of multiple sclerosis patients in recent phase II and III clinical trials.

While dalfampridine is effective in enhancing mobility, it carries a risk of epileptic seizures as a potential adverse effect, highlighting the importance of monitoring patient safety during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dalfampridine in multiple sclerosis. Goodman, AD., Hyland, M.[2017]

The implementation of a prior authorization (PA) program for dalfampridine in patients with multiple sclerosis led to a significant reduction in utilization, with PA members averaging 2.1 fewer claims per member compared to those without PA, indicating improved safety in prescribing practices.

The PA program resulted in a total cost avoidance of $143,010, suggesting that it not only enhances patient safety by ensuring appropriate use but also reduces overall pharmacy expenditures for dalfampridine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dalfampridine prior authorization program: a cohort study. Gleason, PP., Phillips, J., Fenrick, BA., et al.[2023]

Dalfampridine has been shown to improve walking speed in individuals with multiple sclerosis based on three recent randomized controlled trials, indicating its potential efficacy as a treatment.

However, the effectiveness of dalfampridine varies among patients, and there is currently no clear method to identify which patients will benefit significantly from the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing dalfampridine efficacy in the physician's office. Raffel, JB., Malik, O., Nicholas, RS.[2013]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7885571/

Dalfampridine in the treatment of multiple sclerosis: a meta ... The pooled data of MSWS-12 score changes suggested that dalfampridine was associated with slight improvement in walking ability in MS patients.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/20976768/

A phase 3 trial of extended release oral dalfampridine in ... The average improvement in walking speed among dalfampridine-treated TWRs during the 8-week efficacy evaluation period was 24.7% from baseline (95% confidence ...

3. ampyra-hcp.com ampyra-hcp.com/clinical-trials/

Clinical Study Results AMPYRA® (dalfampridine) improved walking speed in significantly more patients than placebo in 2 clinical studies. · 25%. Average increase in walking speed ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S187874792301704X

Enhancing Neural Transmission in Multiple Sclerosis (4- ... Through a series of clinical trials, dalfampridine (dosed at 10 mg twice daily) has been found to improve walking speed by approximately 25 % on average in one ...

5. ijmsc.org ijmsc.org/view/effects-of-physical-therapy-and-dalfampridine-on-function-and-quality-of-life-in-nonambulatory-individuals-with-multiple-sclerosis-a-randomized-controlled-trial

Effects of Physical Therapy and Dalfampridine on Function ... The dalfampridine group did not demonstrate improvement over the placebo group with any outcomes, however, the overall cohort demonstrated ...

6. ampyra-hcp.com ampyra-hcp.com/safety-results/

Safety and Tolerability Profile Adverse reactions in ≥2% of patients treated with AMPYRA® (dalfampridine) and more frequently than in placebo-treated patients in controlled clinical studies ...

7. fda.gov fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-seizure-risk-multiple-sclerosis-patients-who-take-ampyra-dalfampridine

Seizure risk for multiple sclerosis patients who take Ampyra FDA Drug Safety Communication: Seizure risk for multiple sclerosis patients who take Ampyra (dalfampridine) · Ampyra can cause seizures, even if ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/22497693/

The safety profile of dalfampridine extended release in ... In patients with MS, dalfampridine has a narrow therapeutic range but an acceptable safety profile when used at the therapeutic dose of 10 mg twice daily.

9. ampyra.com ampyra.com/app/themes/ampyra/pdf/prescribing-information.pdf

prescribing-information.pdf AMPYRA® (dalfampridine) is a potassium channel blocker indicated to improve walking in adult patients with multiple sclerosis (MS). This was demonstrated by an ...

10. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/26719727/

Safety profile of dalfampridine extended release in multiple ... The 5-year US postmarketing safety data of dalfampridine-ER is consistent with the safety profile observed in clinical trials.