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

Phase 2

Recruiting

• Conditions: Long COVID; Post-Acute COVID-19 Syndrome
• Interventions: Drug: Amantadine; Other: Provider Counseling; Other: Physical, Occupational, Speech Therapy; Other: Medications for symptoms management

• Registration Number: NCT06234462
• Lead Sponsor: University of Texas Southwestern Medical Center

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.

Detailed Description

This study is a prospective, open-label, single-blind, randomized control study. Study duration is approximately 6 weeks starting at the baseline visit. We will recruit 30 participants (15 per arm) for this pilot study.

Study Timeline

• Study First Submitted: 2024-01-08
• Study First Submitted QC: 2024-01-29
• Study First Posted: 2024-01-31
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-07
• Last Update Posted: 2025-05-08
• Study Start: 2025-06
• Primary Completion: 2025-09-01
• Study Completion: 2025-10-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• 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

Exclusion Criteria

• 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Standard of Care	Provider Counseling	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.
Standard of Care + Amantadine	Physical, Occupational, Speech Therapy	Participants in this arm will review standard of care and amantadine.
Standard of Care + Amantadine	Provider Counseling	Participants in this arm will review standard of care and amantadine.
Standard of Care	Physical, Occupational, Speech Therapy	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.
Standard of Care	Medications for symptoms management	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.
Standard of Care + Amantadine	Medications for symptoms management	Participants in this arm will review standard of care and amantadine.
Standard of Care + Amantadine	Amantadine	Participants in this arm will review standard of care and amantadine.

Primary Outcome Measures

Name	Time	Method
Measures of cognitive functioning	4 weeks	Digit Vigilance Test

Secondary Outcome Measures

Name	Time	Method
Measures of fatigue	4 weeks	Physical Subscale of the Modified Fatigue Impact Scale; (MFIS), and fatigue subsection of PROMIS-29.
Measures of anxiety and depression	4-6 weeks	anxiety and depression sections of the PROMIS-29
Measures of endurance and strength	4 weeks	Physical Function subsection of PROMIS-29

Trial Locations

Locations (1)

UT Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States