Amantadine for Cognitive Impairment in Post-COVID Syndrome

(AmantadineLC Trial)

Overseen By Seuli Brill, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Ohio State University

Must not be taking: Kava-kava, others

Disqualifiers: Psychosis, Seizure disorder, Heart failure, 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: 16 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial will test if amantadine can improve thinking and memory problems in people with Long COVID. It will involve 60 participants who have cognitive symptoms. The study will last several months, comparing amantadine to another treatment. Amantadine has been shown to enhance cognitive function in patients with traumatic brain injury and is well tolerated.

Will I have to stop taking my current medications?

You may need to stop taking certain medications if they have adverse interactions with amantadine. The study requires that you are not currently taking any medication that interacts negatively with amantadine.

Is amantadine generally safe for humans?

Amantadine, under various brand names like Gocovri and Osmolex ER, has been used safely in humans for conditions like Parkinson's disease and multiple sclerosis. It has been studied for its safety in treating symptoms related to these conditions, and ongoing research is assessing its safety for COVID-19-related symptoms. ^{1 2 3 4 5}

How is the drug amantadine unique for treating cognitive impairment in post-COVID syndrome?

Amantadine is unique because it has antiviral, anti-inflammatory, and dopaminergic effects, which may help with cognitive impairment by enhancing dopamine release and potentially reducing neurological complications. Unlike other treatments, it has shown benefits in neurodegenerative diseases and may prevent COVID-19 progression, making it a novel option for post-COVID cognitive issues. ^{4 6 7 8 9}

What data supports the effectiveness of the drug amantadine for cognitive impairment in post-COVID syndrome?

Amantadine has shown potential benefits in improving mental status in Alzheimer's patients and has been effective in treating fatigue in multiple sclerosis, which are conditions with cognitive challenges. Additionally, it has antiviral properties that may help prevent COVID-19 progression, suggesting it could be beneficial for cognitive issues related to post-COVID syndrome. ^{4 6 7 9 10}

Who Is on the Research Team?

Andrew I Schamess, MD

Principal Investigator

Ohio State University

Are You a Good Fit for This Trial?

This trial is for adults over 18 who've had COVID-19 and are now experiencing cognitive issues due to Long COVID. They must not be pregnant, breastfeeding, or at risk of pregnancy without birth control. Participants should not have a history of seizures, heart problems, certain mental health conditions, or be on conflicting medications.

Inclusion Criteria

Is willing to abstain from alcohol use for the duration of the study

Is not breastfeeding

If the participant is of child bearing potential, is not pregnant at enrollment based on negative urine pregnancy test

Exclusion Criteria

You have a history of regularly drinking large amounts of alcohol or have been diagnosed with a serious alcohol problem.

Enrolled in any other research study involving intervention for PASC

If the individual is of child-bearing potential, is not consistently using one or more forms of prescribed birth control

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomly assigned to receive either amantadine or placebo for cognitive impairment related to Long COVID

16 weeks

Regular intervals for assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Amantadine

Trial Overview The study tests whether amantadine can improve brain function in people with Long COVID. It involves taking the drug and undergoing cognitive assessments while avoiding alcohol use during the study period.

How Is the Trial Designed?

Group I: Amantadine Experimental Treatment 1 Intervention

Subjects will be treated with amantadine.

Group II: Placebo Placebo Group 1 Intervention

Subjected received placebo identical to amantadine in appearance.

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?

Ohio State University

Lead Sponsor

Trials

891

Recruited

2,659,000+

Published Research Related to This Trial

A clinical trial is underway to evaluate the efficacy and safety of amantadine in preventing the progression of COVID-19 in 200 patients with risk factors, with treatment lasting 14 days.

The study aims to demonstrate that amantadine can significantly reduce the incidence of acute respiratory failure and neurological complications associated with COVID-19, which are critical for improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of amantadine in the prevention of progression and treatment of COVID-19 symptoms in patients infected with the SARS-CoV-2 virus (COV-PREVENT): Study rationale and design. Rejdak, K., Fiedor, P., Bonek, R., et al.[2022]

Amantadine therapy led to significant improvements in mental status for three patients diagnosed with Alzheimer's disease, with two experiencing dramatic reversals from mute and immobile states to being able to speak coherently during treatment.

The observed improvements were linked to changes in EEG patterns, suggesting that amantadine may enhance dopamine release and act as a central stimulant, although the benefits diminished upon withdrawal of the drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amantadine and the end-stage dementia of Alzheimer's type. Erkulwater, S., Pillai, R.[2019]

Amantadine, an existing drug used for neurodegenerative diseases, shows potential antiviral activity against SARS-CoV-2 by inhibiting viral genome release and preventing lung injury, which could be beneficial during the COVID-19 pandemic.

Patients with Parkinson's disease or multiple sclerosis who were treated with amantadine or memantine for several months did not show signs of COVID-19 infection after being confirmed positive for SARS-CoV-2, suggesting a possible prophylactic effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adamantanes for the treatment of neurodegenerative diseases in the presence of SARS-CoV-2. Butterworth, RF.[2023]

In a study of nine patients with confirmed Creutzfeldt-Jakob disease (CJD), four were treated with amantadine hydrochloride for an average of 32 days, but overall survival did not significantly differ from those receiving only supportive care.

Despite no significant impact on survival, three patients treated with amantadine showed temporary improvements in wakefulness and mental function, and EEG changes were noted in two patients, indicating some potential for amantadine to affect brain activity in CJD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of amantadine on arousal and EEG patterns in Creutzfeldt-Jakob disease. Terzano, MG., Montanari, E., Calzetti, S., et al.[2019]

In a review of 30 dementia patients treated with amantadine for executive dysfunction syndrome, 57% showed significant improvement, indicating potential efficacy of the medication in this context.

Amantadine was well tolerated among the patients, many of whom were also on other psychotropic medications, suggesting it could be a safe option for managing executive dysfunction in dementia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amantadine for executive dysfunction syndrome in patients with dementia. Drayton, SJ., Davies, K., Steinberg, M., et al.[2013]

In a Phase 3 trial involving 558 participants with multiple sclerosis (MS), the 274 mg dose of ADS-5102 significantly improved walking speed, with 21.1% of participants showing a meaningful response compared to 11.3% in the placebo group.

While the primary outcome was met, indicating efficacy, there was a notable increase in adverse events leading to discontinuation, particularly at the higher dose (20.5% for 274 mg), suggesting a need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 3, double-blind, placebo-controlled efficacy and safety study of ADS-5102 (Amantadine) extended-release capsules in people with multiple sclerosis and walking impairment. Cohen, JA., Cameron, MH., Goldman, MD., et al.[2022]

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]

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 randomized, placebo-controlled study involving 186 patients with COVID-19 found that amantadine did not improve recovery times compared to placebo, with both groups showing a median recovery time of 10 days.

The study was terminated early due to a lack of efficacy, and there were no significant differences in mortality or intensive care requirements between the amantadine and placebo groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of oral amantadine among patients hospitalised with COVID-19: A randomised, double-blind, placebo-controlled, multicentre study. Barczyk, A., Czajkowska-Malinowska, M., Farnik, M., et al.[2023]

Citations

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

The use of amantadine in the prevention of progression and treatment of COVID-19 symptoms in patients infected with the SARS-CoV-2 virus (COV-PREVENT): Study rationale and design. [2022]

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

Amantadine and the end-stage dementia of Alzheimer's type. [2019]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Adamantanes for the treatment of neurodegenerative diseases in the presence of SARS-CoV-2. [2023]

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

The effect of amantadine on arousal and EEG patterns in Creutzfeldt-Jakob disease. [2019]

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

Amantadine for executive dysfunction syndrome in patients with dementia. [2013]

6. England pubmed.ncbi.nlm.nih.gov

A Phase 3, double-blind, placebo-controlled efficacy and safety study of ADS-5102 (Amantadine) extended-release capsules in people with multiple sclerosis and walking impairment. [2022]

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

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

8. 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]

9. 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]

10. England pubmed.ncbi.nlm.nih.gov

Efficacy of oral amantadine among patients hospitalised with COVID-19: A randomised, double-blind, placebo-controlled, multicentre study. [2023]