Amantadine for Long COVID

Overseen By Brittany Wright

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Texas Southwestern Medical Center

Disqualifiers: Psychosis, Epilepsy, Severe depression, 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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether amantadine, a medication, can alleviate symptoms of long COVID. Researchers aim to determine if it can reduce symptoms such as brain fog, tiredness, and trouble focusing. Participants will receive either amantadine with their usual care or just their usual care to compare effects. Those who had a confirmed COVID test within the last year and experience issues like memory problems or physical fatigue might be suitable candidates. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that amantadine has been studied for safety in treating symptoms related to COVID-19. One study found that amantadine was generally well-tolerated and might help reduce fatigue in people recovering from COVID-19. While no severe side effects were reported when using it for post-COVID-19 symptoms, research continues to ensure its safety for these specific conditions.

The FDA has already approved amantadine for other uses, such as treating Parkinson's disease and certain types of flu, which means its safety is well-known. This provides some reassurance about its use, but it's important to remember that current studies specifically examine its effects and safety for long COVID symptoms. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for Long COVID, which typically includes physical therapy, occupational therapy, speech-language pathology, counseling, and targeted medications, Amantadine offers a fresh approach. Amantadine is unique because it has antiviral and neuroprotective properties that may help alleviate persistent symptoms by modulating neurotransmitter activity, which is not the focus of current treatments. Researchers are excited about Amantadine because it targets different underlying mechanisms of Long COVID, offering hope for more comprehensive symptom relief.

What evidence suggests that amantadine might be an effective treatment for long COVID?

Research into using amantadine for long COVID, also known as post-acute sequelae of COVID-19 (PASC), continues. In this trial, one group of participants will receive standard care plus amantadine, while another group will receive only standard care. Some reports suggest that amantadine might help with brain-related symptoms like memory and attention problems. It has previously treated Parkinson's disease, which involves similar issues. However, a recent study found that amantadine does not affect the progression of COVID-19 itself. While these observations offer some hope, more evidence is needed to confirm its effectiveness for long COVID symptoms. ^{2 3 4 6 7}

Who Is on the Research Team?

Amy Mathews, M.D.

Principal Investigator

UT Southwestern Medical Center

Are You a Good Fit for This Trial?

This trial is for English-speaking adults aged 20-65 who had a confirmed COVID-19 test result between 8 weeks and one year before the initial visit. It's aimed at those experiencing long-COVID symptoms like decreased endurance, fatigue, weakness, depression, or anxiety.

Inclusion Criteria

I am between 20 and 65 years old.

Can provide informed consent

Confirmed COVID+ test (either rapid antigen or PCR) between 8 weeks and one year prior to initial visit

Exclusion Criteria

Known hypersensitivity to amantadine

Clinically significant psychiatric, neurologic, renal, hepatic, ophthalmologic, cardiac impairment in the opinion of the investigators, including but not limited to: Psychiatric: Acute or chronic unstable Axis I psychiatric illness History of psychosis Severe depression Patient Health Questionnaire-9 (PHQ-9) score >= 20 Suicidality Neurologic: Epilepsy Cognitive dysfunction predating COVID infection History of delirium Neurologic conditions with agitation or confusion

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive amantadine or standard of care for cognitive dysfunction in long-COVID

6 weeks

Baseline visit and regular follow-ups

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 help reduce symptoms and improve cognitive function and endurance in 'long-hauler' COVID patients. Participants will also receive counseling and may engage in physical, occupational, or speech therapy as part of their treatment.

How Is the Trial Designed?

Group I: Standard of Care + Amantadine Experimental Treatment 4 Interventions

Participants in this arm will review standard of care and amantadine.

Group II: Standard of Care Active Control 3 Interventions

Participants in this arm will receive current standard of care for PASC symptoms which may include: PT, OT, SLP, provider counseling, and/or pharmacologic interventions for targeted symptom management.

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 Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Published Research Related to This Trial

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 the ALLAY-LID II trial, IR/ER-amantadine significantly reduced levodopa-induced dyskinesia (LID) compared to placebo, with a notable improvement in Unified Dyskinesia Rating Scale (UDysRS) scores for both 193 mg and 258 mg doses.

The 258 mg dose of IR/ER-amantadine also increased the time patients spent ON without troublesome dyskinesia, although some participants experienced adverse effects like hallucinations, leading to a discontinuation rate of 18.7%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immediate-release/extended-release amantadine (OS320) to treat Parkinson's disease with levodopa-induced dyskinesia: Analysis of the randomized, controlled ALLAY-LID studies. Rascol, O., Tönges, L., deVries, T., 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]

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]

ADS-5102 (amantadine extended release) significantly reduces dyskinesia and OFF time in Parkinson's disease patients, showing sustained effects over a treatment duration of up to two years, particularly in those switched from immediate-release amantadine.

The safety profile of ADS-5102 remains consistent with previous studies, indicating that it can provide additional benefits without increasing adverse events for patients transitioning from amantadine IR.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Parkinson's Patients with Dyskinesia Switched from Immediate Release Amantadine to Open-label ADS-5102. Isaacson, SH., Fahn, S., Pahwa, R., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10284620/

Amantadine for COVID-19 treatment (ACT study) Conclusions. We found no effect of amantadine on disease progression of SARS-CoV-2 infection. Keywords: Amantadine COVID-19, ...

2. 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.

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

Amantadine for Cognitive Impairment in Post-COVID ... The study aims to demonstrate that amantadine can significantly reduce the incidence of acute respiratory failure and neurological complications associated with ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9735925/

Psychotic Disorders in the Course of SARS-CoV-2 Infection or ... Single reports [17,18,19] suggest the effectiveness of amantadine in the treatment of COVID-19. Amantadine has been used for the treatment of Parkinson's ...

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/PMC11493926/

Post-acute sequelae of SARS-CoV-2 infection (Long COVID ... Long COVID, also known as PASC (post-acute sequelae of SARS-CoV-2), is a complex infection-associated chronic condition affecting tens of millions of people ...

7. researchgate.net researchgate.net/publication/377441707_A_randomized_open-label_clinical_trial_on_the_effect_of_Amantadine_on_post_Covid_19_fatigue

(PDF) 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. The ...