Amantadine for Stroke Recovery

(PRESTA Trial)

Overseen By Nichole Gallatti, M.S.Ed.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Pennsylvania

Must not be taking: Anticholinergics, Neuroleptics

Disqualifiers: Aphasia, Dementia, Pregnancy, Seizures, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether amantadine can aid stroke recovery. Participants will receive either amantadine or a placebo (a pill with no active drug) for one month, with progress monitored over three months. The trial seeks individuals who have had a stroke recently (within the last three weeks) and are ready for rehabilitation or a special home program. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group.

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 participate if you are taking certain medications like primary anticholinergic drugs or have a history of neuroleptic use.

Is there any evidence suggesting that amantadine is likely to be safe for humans?

Research has shown that amantadine is generally safe for use. It already treats Parkinson's disease and some flu symptoms. In other studies, participants took amantadine for up to 24 weeks and experienced manageable side effects.

Common side effects include dizziness, dry mouth, and trouble sleeping. More serious issues, like heat stroke, have been reported but are rare. Staying cool and drinking plenty of water while taking this medication is important, especially in hot weather. Individuals with kidney issues should consult a doctor before starting amantadine.

Overall, evidence suggests that amantadine is safe for many, but individual reactions can vary. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for stroke recovery?

Most treatments for stroke recovery focus on physical rehabilitation and medications that improve blood flow or reduce complications. But Amantadine offers a different approach. It's unique because it acts on the brain's neurotransmitter systems, particularly dopamine, which may enhance cognitive and motor recovery post-stroke. Researchers are excited about Amantadine because it might speed up recovery and improve outcomes in ways that traditional treatments don't, potentially offering a new avenue for stroke survivors to regain function more effectively. Additionally, its oral administration makes it easy to use alongside existing therapies.

What evidence suggests that amantadine might be an effective treatment for stroke recovery?

Research has shown that amantadine, which participants in this trial may receive, can aid recovery after a stroke. In one study, 86.9% of patients who took amantadine showed improved alertness, compared to 54% in a group that did not take it. This finding suggests that amantadine can help reawaken parts of the brain that become less active after a stroke. Additionally, amantadine has proven effective in helping people recover from brain injuries by improving their ability to manage daily activities. While this differs from stroke recovery, it indicates that amantadine might have a similar positive effect on the brain. ^{3 6 7 8 9}

Are You a Good Fit for This Trial?

Adults aged 18-85 who've had a recent stroke (ischemic or hemorrhagic) and are in stable condition with mild to moderate impairment can join. They must have good kidney function, be able to swallow, and participate in tests. Excluded are those with severe communication difficulties, cognitive impairments before the stroke, certain medical conditions like active cancer or Parkinson's disease, prior amantadine use, or current participation in other drug trials.

Inclusion Criteria

My kidneys are functioning well, with a creatinine clearance rate of 60 mL/min or more.

Able to participate in administered tests

Your stroke severity score is between 3 and 15 on the NIH Stroke Scale.

Exclusion Criteria

I have Parkinson's disease.

I am currently taking medication for muscle spasms or bladder issues.

I have had seizures in the past.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either amantadine or placebo for 1 month

4 weeks

Regular visits for monitoring and questionnaires

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

Periodic assessments including cognitive and physical evaluations

What Are the Treatments Tested in This Trial?

Interventions

• Amantadine

Trial Overview

The trial is testing if amantadine helps stroke recovery compared to a placebo. Participants will randomly receive either the drug or placebo for one month and will be monitored for three months total through exams and questionnaires assessing their recovery progress.

How Is the Trial Designed?

Group I: Amantadine Active Control 1 Intervention

100 mg amantadine twice daily, or if 65 years or older once daily

Group II: Placebo Placebo Group 1 Intervention

placebo pill, twice daily

Amantadine is already approved in United States, Canada, European Union for the following indications:

Approved in United States as Symmetrel for:

• Parkinson's disease
• Extrapyramidal reactions
• Influenza A virus infections

Approved in United States as Gocovri for:

• Dyskinesia in patients with Parkinson's disease

Approved in United States as Osmolex ER for:

• Parkinson's disease
• Drug-induced extrapyramidal reactions

Approved in Canada as Symmetrel for:

• Parkinson's disease
• Extrapyramidal reactions
• Influenza A virus infections

Approved in European Union as Symmetrel for:

• Parkinson's disease
• Extrapyramidal reactions

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Published Research Related to This Trial

In a study involving 196 levodopa-treated Parkinson's disease patients, Gocovri (amantadine) showed significant improvements in non-motor symptoms like daytime sleepiness and depression compared to placebo, suggesting its efficacy beyond just managing dyskinesia.

The analysis indicated that improvements in non-motor symptoms correlated with reductions in dyskinesia, highlighting a potential mechanism of action where alleviating dyskinesia may also benefit other aspects of Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Gocovri (Amantadine) Extended Release Capsules on Non-Motor Symptoms in Patients with Parkinson's Disease and Dyskinesia. Mehta, SH., Pahwa, R., Tanner, CM., et al.[2021]

In two phase 3 clinical trials involving 196 participants, Gocovri significantly improved patient-perceived disability related to daily living activities in Parkinson's disease, with a mean change of -3.4 in MDS-UPDRS Part II scores compared to -1.4 for placebo (P = 0.004).

The improvements with Gocovri were particularly notable in specific motor symptoms such as freezing, tremor, and difficulties with getting out of bed or eating, indicating its efficacy in enhancing daily functioning for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Gocovri (Amantadine) Extended-Release Capsules on Motor Aspects of Experiences of Daily Living in People with Parkinson's Disease and Dyskinesia. Hauser, RA., Mehta, SH., Kremens, D., et al.[2022]

Amantadine hydrochloride, at doses of 2.5 and 5 mg/kg, significantly reduced the stimulating effects of d-amphetamine on motor activity in mice, indicating its potential to modulate CNS stimulation.

Additionally, amantadine increased the anorexic effects of d-amphetamine, as shown by reduced milk intake, suggesting it may influence appetite regulation in the context of stimulant use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amantadine decreases d-amphetamine stimulation and increases d-amphetamine anorexia in mice. Clark, R., Smith, DH., Vernier, VG., et al.[2020]

A study on the pharmacokinetics of extended-release amantadine involved adults with varying degrees of renal function, showing that renal impairment significantly reduces the clearance of amantadine from the body.

Pharmacokinetic modeling suggested tailored dosing regimens for amantadine based on renal function, allowing for effective treatment while maintaining safety in patients with impaired kidney function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Renal Impairment on the Pharmacokinetics of Once-Daily Amantadine Extended-Release Tablets. deVries, T., Dentiste, A., Di Lea, C., et al.[2020]

A 65-year-old woman with Parkinsonism who did not respond to standard treatments like levodopa and bromocriptine showed significant improvement in motor and mental function after being treated with amantadine (200 mg/day).

This case highlights amantadine's potential as an effective alternative therapy for patients with Parkinsonism who are resistant to conventional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amantadine for levodopa resistant parkinsonism. Sandyk, R., Iacono, RP., Snider, SR.[2019]

In a 2-year open-label trial involving 223 patients with Parkinson's disease, Gocovri (amantadine) demonstrated long-term safety and tolerability, with 75.8% of participants completing one year of treatment.

Gocovri effectively reduced motor complications, such as dyskinesia and OFF time, maintaining low scores on the Movement Disorder Society-Unified Parkinson's Disease Rating Scale throughout the trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EASE LID 2: A 2-Year Open-Label Trial of Gocovri (Amantadine) Extended Release for Dyskinesia in Parkinson's Disease. Tanner, CM., Pahwa, R., Hauser, RA., et al.[2021]

Citations

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pmc.ncbi.nlm.nih.gov/articles/PMC11389468/

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In the analysis, AMT-ER demonstrated the most significant benefit, with a 27.3% improvement in UDysRS scores and a 36.1% reduction in OFF time— ...

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frontiersin.org

frontiersin.org/journals/neurology/articles/10.3389/fneur.2021.645706/full

Pooled Analyses From Pivotal Trials in Parkinson's Disease

Conclusions: Gocovri treatment more than doubled the daily time patients spent ON without dyskinesia. These results suggest that the Gocovri ...

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accessdata.fda.gov/drugsatfda_docs/label/2017/208944lbl.pdf

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clinicaltrials.gov

clinicaltrials.gov/study/NCT05140148

Promoting Recovery After STroke With Amantadine

Also called a data safety and monitoring board, or DSMB. Early Phase 1 (formerly listed as Phase 0). A phase of research used to describe exploratory trials ...

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mayoclinic.org

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Amantadine (oral route) - Side effects & dosage

Amantadine is an antidyskinetic medicine. It is used to treat Parkinson's disease (sometimes called paralysis agitans or shaking palsy) and its symptoms.

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Amantadine: Uses, Dosage, Side Effects, Warnings

Heat stroke has happened in people taking amantadine. Be careful in hot weather and during physical activity. If you have kidney problems, talk ...