Amantadine for Cognitive Impairment in Post-COVID Syndrome

(AmantadineLC Trial)

Overseen By Shan-Lu Liu, PhD

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 tests whether amantadine, a medication, can improve brain function in individuals with Long COVID. Researchers aim to determine if amantadine can alleviate thinking and memory issues and explore the causes of these cognitive symptoms. Participants will receive either amantadine or a placebo (a pill that resembles the real medication but has no effect) to compare outcomes. Suitable candidates have experienced thinking or memory problems since contracting COVID-19 and are not currently taking medications that adversely interact with amantadine. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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

Research has shown that people usually tolerate amantadine well. Past patients found its side effects manageable. Studies suggest that amantadine may help protect against severe COVID-19, supporting its safety. Notably, the FDA has already approved amantadine for treating other conditions, such as Parkinson’s disease and some types of flu, indicating its general safety. However, like any medication, it can have side effects, so discussing these with a healthcare provider is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Long COVID?

Unlike the standard treatments for cognitive impairment in post-COVID syndrome, which typically include cognitive rehabilitation therapies and medications like stimulants or cholinesterase inhibitors, amantadine offers a different approach. Researchers are excited about amantadine because it acts on the brain's dopamine system, which is not the primary target of most current therapies for this condition. This unique mechanism of action might help improve cognitive function more effectively or in a different way than existing options. This potential to address cognitive issues through a novel pathway is what sets amantadine apart and fuels the excitement surrounding its use for post-COVID cognitive impairment.

What evidence suggests that amantadine might be an effective treatment for cognitive impairment in Long COVID?

Research has shown that amantadine, which participants in this trial may receive, might help with tiredness and cognitive issues in people with Long COVID. One study found that amantadine significantly reduced tiredness in individuals recovering from COVID. Although primarily used to treat Parkinson's disease and flu symptoms, researchers are now exploring its potential to alleviate post-COVID brain fog. The treatment alters certain brain chemicals, which might improve memory and focus. While more research is needed, early results offer promise for those experiencing cognitive issues after COVID-19. ^{1 2 6 7 8}

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]

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]

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]

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]

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 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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06055244

Study Details | NCT06055244 | Amantadine Therapy for ... This study will enroll 60 subjects with Long COVID and cognitive symptoms such as problems with memory, concentration, speech and attention, and brain fog.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38228731/

A randomized open-label clinical trial on the effect of ... In this study, we report the safety, tolerability, and substantial fatigue-relieving effects of Amantadine in post-COVID-19 fatigue.

3. withpower.com withpower.com/trial/phase-1-covid-19-9-2023-95c05

Amantadine for Cognitive Impairment in Post-COVID ... 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 ...

4. researchgate.net researchgate.net/publication/373159963_Amantadine_in_unvaccinated_patients_with_early_mild_to_moderate_COVID-19_A_randomized_placebo-controlled_double-blind_trial

(PDF) Amantadine in unvaccinated patients with early, mild ... We aimed to evaluate the effectiveness of amantadine in preventing the progression of COVID‐19 and its neurological sequelae. Methods Unvaccinated patients with ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06234462

A Study of Amantadine for Cognitive Dysfunction in ... Purpose: To decrease symptom burden, improve cognitive function, improve endurance, and decrease fatigue in subjects with post-acute sequelae of COVID-19 (PASC) ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12154266/

COVID-19 Pandemic Waves and 2024–2025 Winter ... Conclusions: These findings suggest a potential protective effect of ACEI, ARBs, and amantadine against severe COVID-19 and support the safety ...

7. withpower.com withpower.com/trial/phase-2-post-acute-covid-19-syndrome-3-2024-68a27

Amantadine for Long COVID · Info for Participants ... Amantadine will have tolerable side effects & efficacy for patients with Post-COVID Syndrome, Long COVID Syndrome and COVID-19. Learn more about the study.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10310313/

Long COVID: Complications, Underlying Mechanisms, and ... In this article, we provide an overview of some of the main mechanisms by which long Covid induces end-organ damage proposed in recent research studies.