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

Feasibility Study of Amantadine for Cognitive Dysfunction in Patients With Long-Covid: A Pilot Randomized Control 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.

Study Overview

• Status: Not yet recruiting
• Conditions: Long COVID; Post-Acute COVID-19 Syndrome
• Intervention / Treatment: Other: Physical, Occupational, Speech Therapy; Other: Provider Counseling; Other: Medications for symptoms management; Drug: Amantadine

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 Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Brittany Wright, PhD; Phone Number: 469-892-8637; Email: brittany.wright@utsouthwestern.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard of Care; 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; 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.; Other: Provider Counseling; Clinic providers will provide counseling/education on Long-COVID.; Other: Medications for symptoms management; 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.
Experimental: Standard of Care + Amantadine; Participants in this arm will review standard of care and amantadine.	Other: Physical, Occupational, Speech Therapy; 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.; Other: Provider Counseling; Clinic providers will provide counseling/education on Long-COVID.; Other: Medications for symptoms management; 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.; Drug: Amantadine; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measures of endurance and strength	6 Minute Walk Test (6MWT)	4 weeks
Measures of endurance and strength	30 second sit-to-stand	4 weeks
Measures of endurance and strength	grip strength grip strength	4 weeks
Measures of endurance and strength	Physical Function subsection of PROMIS-29	4 weeks
Measures of fatigue	Physical Subscale of the Modified Fatigue Impact Scale (MFIS), and fatigue subsection of PROMIS-29.	4 weeks
Measures of anxiety and depression	Patient Health Questionnaire-9 (PHQ-9)	4-6 weeks
Measures of anxiety and depression	Generalized Anxiety DIsorder-7 (GAD-7) questionnaires	4-6 weeks
Measures of anxiety and depression	anxiety and depression sections of the PROMIS-29	4-6 weeks

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Investigators: Principal Investigator: Amy Mathews, M.D., UT Southwestern Medical Center

Study record dates

Study Major Dates

• Study Start (Estimated): May 13, 2024
• Primary Completion (Estimated): May 1, 2025
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: January 8, 2024
• First Submitted That Met QC Criteria: January 29, 2024
• First Posted (Actual): January 31, 2024

Study Record Updates

• Last Update Posted (Actual): May 6, 2024
• Last Update Submitted That Met QC Criteria: May 3, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Neurocognitive Disorders; Disease Attributes; Cognition Disorders; Chronic Disease; Post-Infectious Disorders; COVID-19; Cognitive Dysfunction; Post-Acute COVID-19 Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Antiviral Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Amantadine
• Other Study ID Numbers: STU-2023-0234

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No