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

Trial Summary

What is the purpose of this trial?

The investigators aim to examine whether amantadine can help patients recover from stroke. This will be a blinded randomized clinical trial (RCT). Patients will be randomized post-ischemic or hemorrhagic stroke either to the placebo arm or amantadine arm. Patients will be on study drug or placebo for 1 month but will be enrolled for 3 months total. At various time points patients will be examined and fill out questionnaires to determine level of stroke recovery.

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.

What data supports the effectiveness of the drug Amantadine for stroke recovery?

Amantadine has been shown to improve motor and mental symptoms in Parkinson's disease, which suggests it might help with similar issues in stroke recovery. It is used to manage movement problems and improve daily living activities in Parkinson's patients, indicating potential benefits for stroke patients with similar challenges. ^{1 2 3 4 5}

Is Amantadine generally safe for humans?

Amantadine, known by names like Symmetrel, Gocovri, and Osmolex ER, is approved for treating Parkinson's disease and related conditions, indicating it has been evaluated for safety in humans. It is used at specific doses and has shown effects on motor symptoms and mental status, suggesting it is generally safe when used as directed. ^{2 3 4 5 6}

How is the drug Amantadine unique for stroke recovery?

Amantadine is unique because it is an extended-release formulation that has been used to treat Parkinson's disease and drug-induced movement disorders, suggesting it may help with motor recovery in stroke patients. Its ability to improve motor function and mental status in Parkinson's patients could offer similar benefits for stroke recovery. ^{1 2 3 4 5}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. New Zealand 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. [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Effects of Gocovri (Amantadine) Extended Release Capsules on Non-Motor Symptoms in Patients with Parkinson's Disease and Dyskinesia. [2021]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Effects of Renal Impairment on the Pharmacokinetics of Once-Daily Amantadine Extended-Release Tablets. [2020]

4. Netherlands 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. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Amantadine for levodopa resistant parkinsonism. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Amantadine decreases d-amphetamine stimulation and increases d-amphetamine anorexia in mice. [2020]