Amantadine Therapy for Cognitive Impairment in Long COVID

NCT06055244 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: 2023H0268GF317855
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

This study will look at the effects of amantadine on cognitive function in persons with Long COVID. It will also collect specimens to study possible causes of cognitive symptoms in Long COVID, and whether any lab tests can predict who will respond better to amantadine.

Conditions

Long COVID; Post-COVID19 Condition; Post-Acute COVID19 Syndrome

Keywords

long covid; PASC; post COVID condition; cognition; brain fog; amantadine

Outcome Measures

Primary Outcomes (2)

• Improvement in cognitive symptoms

  Improvement in scores on self-assessment of overall cognitive functioning

  4 months

• Improvement on objective cognitive testing

  Subjects will be administered battery of cognitive tests to determine if there is a change in objective cognitive function

  4 months

Secondary Outcomes (2)

• Mood symptoms

  4 months

• Medication tolerability

  4 months

Study Arms (2)

Amantadine

EXPERIMENTAL

Subjects will be treated with amantadine.

Drug: Amantadine

Placebo

PLACEBO COMPARATOR

Subjected received placebo identical to amantadine in appearance.

Drug: Amantadine

Interventions

Amantadine DRUG

Subjects will be give amantadine 100 mg twice daily.

Amantadine; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age and above at the signing of informed consent
• Had a positive laboratory or home test for COVID19 within one year prior to signing of informed consent, with subsequent symptoms meeting criteria for PASC.
• Subjective Cognitive impairment associated with PASC
• Cognitive symptoms will be formally assessed at a pre-enrollment visit using the PROMIS Cognitive Function Questionnaire (CGQ) and the PROMIS Cognitive Abilities subset (CAS), which are validated patient-reported measures of subjective cognitive functioning. Potential participants must have a cumulative score less than 60 (indicating at least mild subjective cognitive dysfunction) to be eligible.
• Is willing and able to comply with study visits and study-related procedures/assessments.
• Is able to provide informed consent to participate in the study 5.
• Is not currently taking a medication with adverse interactions with amantadine. (Table 2)
• If the participant is of child bearing potential, , is not pregnant at enrollment based on negative urine pregnancy test.
• If the participant is of child-bearing potential, is consistently using one or more forms of prescribed birth control, such as an oral contraceptive, intrauterine device or a long-acting reversible contraceptive.
• Is not breastfeeding.
• Is willing to abstain from alcohol use for the duration of the study.
• Endorses self-reported cognitive impairment on the PROMIS CF\[40\].
• Does not have any other contraindications to amantadine use as noted in section 6 below or as identified by the study clinician investigators.

You may not qualify if:

• At risk for complications of study drug with conditions such as:
• Lifetime history of compulsive or impulsive behavior: Compulsive gambling, hypersexuality, binge eating; suicidality.
• Underweight, malnourished at time of enrollment.
• History of restrictive eating disorder within 3 months prior to consent.
• Lifetime history of heart failure or diagnosed cardiac arrhythmia.
• Untreated angle closure glaucoma at time of enrollment.
• Lifetime history of psychosis or psychotic disorder.
• Lifetime history of seizure disorder.
• Known allergy to amantadine.
• History of binge drinking, heavy alcohol use, or alcohol use disorder as defined by the National Institute on Alcohol Abuse and Alcoholism (NIAAA)\[54\] and the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)\[55\].
• Use of kava-kava within 3 months prior to consent.
• Breastfeeding at screening or expected to be breastfeeding during study period.
• Pregnant at time of screening or expecting to become pregnant during the study period.
• Is taking a medication that adversely interacts with amantadine (see Table 2)
• Has any physical examination findings, and/or history of any illness, concomitant medications or recent live vaccines that, in the opinion of the study investigator, might confound the results of the study or pose an additional risk to the subject by their participation in the study.

Sponsors & Collaborators

• Ohio State University: lead

Study Sites (1)

The Ohio State University Medical Center

Columbus, Ohio, 43221, United States

Location

MeSH Terms

Conditions

Post-Acute COVID-19 Syndrome; Mental Fatigue

Interventions

Amantadine

Condition Hierarchy (Ancestors)

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Fatigue; Signs and Symptoms; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Andrew I Schamess, MD

  Ohio State University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor - Clinical

Model Details: Pilot randomized clinical trial

Study Record Dates

• First Submitted: September 22, 2023
• First Posted: September 26, 2023
• Study Start: December 7, 2023
• Primary Completion: December 11, 2025
• Study Completion: December 29, 2025
• Last Updated: January 27, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Upon study completion
• Access Criteria: As appropriate

Locations

US (1)