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

30 Participants Needed

Trial Summary

What is the purpose of this trial?

Purpose: To decrease symptom burden, improve cognitive function, improve endurance, and decrease fatigue in subjects with post-acute sequelae of COVID-19 (PASC) or "long-hauler" COVID using amantadine. If amantadine use is determined to be efficacious in this population, the findings of this study will be used towards a subsequent randomized control trial.

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.

What data supports the effectiveness of the drug Amantadine for Long COVID?

Amantadine has been shown to improve motor symptoms and mental status in Parkinson's disease, suggesting it may have potential benefits for neurological symptoms in Long COVID, although direct evidence for Long COVID is not provided. ^{1 2 3 4 5}

How is the drug Amantadine unique for treating Long COVID?

Amantadine is unique because it is an extended-release formulation originally used for Parkinson's disease, which may offer a novel approach for Long COVID by potentially improving symptoms through its effects on the brain and nervous system. ^{1 2 4 5 6}

Research Team

Amy Mathews, M.D.

Principal Investigator

UT Southwestern Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

References

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

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

2. 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]

3. 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]

4. England pubmed.ncbi.nlm.nih.gov

Amantadine for levodopa resistant parkinsonism. [2019]

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

Parkinson's Patients with Dyskinesia Switched from Immediate Release Amantadine to Open-label ADS-5102. [2022]

6. England 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. [2022]