A Study of Amantadine for Cognitive Dysfunction in Patients With Long-Covid

NCT06234462 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: STU-2023-0234
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Long COVID; Post-Acute COVID-19 Syndrome

Outcome Measures

Primary Outcomes (6)

• Measures of cognitive functioning

  Repeatable Battery for the Assessment of Neuropsychological Status (R BANS) Self-reported percent back to normal, FAS, Trails A\&B, and Digit Vigilance Test (DVT)

  4 weeks

• Measures of cognitive functioning

  Cognitive Subscale of Modified Fatigue Impact Scale (MFIS)

  4 weeks

• Measures of cognitive functioning

  Self-reported percent back to normal

  4 weeks

• Measures of cognitive functioning

  FAS Test

  4 weeks

• Measures of cognitive functioning

  Trails A \& B

  4 weeks

• Measures of cognitive functioning

  Digit Vigilance Test

  4 weeks

Secondary Outcomes (8)

• Measures of endurance and strength

  4 weeks

• Measures of endurance and strength

  4 weeks

• Measures of endurance and strength

  4 weeks

• Measures of endurance and strength

  4 weeks

• Measures of fatigue

  4 weeks

Study Arms (2)

Standard of Care

ACTIVE COMPARATOR

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.

Other: Physical, Occupational, Speech Therapy; Other: Provider Counseling; Other: Medications for symptoms management

Standard of Care + Amantadine

EXPERIMENTAL

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

Drug: Amantadine; Other: Physical, Occupational, Speech Therapy; Other: Provider Counseling; Other: Medications for symptoms management

Interventions

Amantadine DRUG

Participants that have been randomized to the study group will be instructed to begin taking amantadine on the day after this study visit. They will self-administer amantadine 100 mg twice daily (morning and noon) for four weeks

Standard of Care + Amantadine

Physical, Occupational, Speech Therapy OTHER

Physical Therapy (PT) and Occupational Therapy (OT) train patients on breathing exercises and gradual reconditioning. Patients are referred to speech therapy (SLP) for cognitive remediation and metacognitive strategies.

Standard of Care; Standard of Care + Amantadine

Provider Counseling OTHER

Clinic providers will provide counseling/education on Long-COVID.

Standard of Care; Standard of Care + Amantadine

Medications for symptoms management OTHER

Clinic providers may recommend targeted pharmacologic management for symptoms the patient is experience. As an example, if a patient reports a headache the provider may recommend over-the-counter or prescription medications to target this particular symptom.

Standard of Care; Standard of Care + Amantadine

Eligibility Criteria

• Age: 20 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 20-65
• Can provide informed consent
• Confirmed COVID+ test (either rapid antigen or PCR) between 8 weeks and one year prior to initial visit.
• Able to consent in English
• Endorse symptoms during their initial evaluation and history with the provider that began around the time of the acute COVID19 infection (subjective) including cognitive changes such as cognitive fatigue, brain fog, memory issues,attention issues AND have symptoms in at least 1 out of the 2 following symptom categories:
• Category 1: Decreased endurance, physical fatigue, weakness
• Category 2: Depression, anxiety

You may not qualify if:

• Known hypersensitivity to amantadine
• Clinically significant psychiatric, neurologic, renal, hepatic, opthalmologic, 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

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead

Study Sites (1)

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Post-Acute COVID-19 Syndrome

Interventions

Amantadine; Restraint, Physical; Speech Therapy; Dosage Forms; Palliative Care

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

Intervention Hierarchy (Ancestors)

Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Behavior Control; Therapeutics; Immobilization; Investigative Techniques; Rehabilitation of Speech and Language Disorders; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Pharmaceutical Preparations; Technology, Pharmaceutical; Health Services; Health Care Facilities Workforce and Services

Study Officials

• Amy Mathews, M.D.

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: January 8, 2024
• First Posted: January 31, 2024
• Study Start: June 1, 2025
• Primary Completion: September 1, 2025
• Study Completion: October 1, 2025
• Last Updated: August 26, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)