Long COVIDPhase 2NCT06234462
A Study of Amantadine for Cognitive Dysfunction in Patients With Long-Covid
A Phase 2 study testing Amantadine, Physical, Occupational, Speech Therapy and Provider Counseling in people with Long COVID and Post-Acute COVID-19 Syndrome, run by University of Texas Southwestern Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 to 65 years
- Conditions the study is for
- Long COVID, Post-Acute COVID-19 Syndrome
- What is being tested?
- Amantadine, Physical, Occupational, Speech Therapy and Provider Counseling
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2025to 1 Oct 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- Suicidality
- Neurologic:
- Epilepsy
- Cognitive dysfunction predating COVID infection
- History of delirium
- Neurologic conditions with agitation or confusion
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Long COVID, Post-Acute COVID-19 Syndrome
- Being tested
- Amantadine, Physical, Occupational, Speech Therapy, Provider Counseling, Medications for symptoms management
- Medical subject headings
- Post-Acute COVID-19 Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AmantadineDrug
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
Physical, Occupational, Speech TherapyOther
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.
Provider CounselingOther
Clinic providers will provide counseling/education on Long-COVID.
Medications for symptoms managementOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Amantadine; Other: Physical, Occupational, Speech Therapy; Other: Provider Counseling; Other: Medications for symptoms management |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 4 weeks
Measures of cognitive functioning
Cognitive Subscale of Modified Fatigue Impact Scale (MFIS)
Measured: 4 weeks
Measures of cognitive functioning
Self-reported percent back to normal
Measured: 4 weeks
Measures of cognitive functioning
FAS Test
Measured: 4 weeks
Measures of cognitive functioning
Trails A \& B
Measured: 4 weeks
Measures of cognitive functioning
Digit Vigilance Test
Measured: 4 weeks
Secondary outcomes (8)
Measures of endurance and strength
6 Minute Walk Test (6MWT)
Measured: 4 weeks
Measures of endurance and strength
30 second sit-to-stand
Measured: 4 weeks
Measures of endurance and strength
grip strength
grip strength
Measured: 4 weeks
Measures of endurance and strength
Physical Function subsection of PROMIS-29
Measured: 4 weeks
Measures of fatigue
Physical Subscale of the Modified Fatigue Impact Scale
(MFIS), and fatigue subsection of PROMIS-29.
Measured: 4 weeks
Measures of anxiety and depression
Patient Health Questionnaire-9 (PHQ-9)
Measured: 4-6 weeks
Measures of anxiety and depression
Generalized Anxiety DIsorder-7 (GAD-7) questionnaires
Measured: 4-6 weeks
Measures of anxiety and depression
anxiety and depression sections of the PROMIS-29
Measured: 4-6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2024
- Study startJun 2025 (estimated)
- Primary completion1 Sep 2025 (estimated)
- Study completion1 Oct 2025 (estimated)
Why it stopped: challenges with recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Long COVIDStudies of the same condition, open and under way.
- More trials run by University of Texas Southwestern Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Amy Mathews, University of Texas Southwestern Medical Center
- Investigators
- Amy Mathews, M.D., Principal investigator, University of Texas Southwestern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06234462
- Sponsor's protocol ID
- STU-2023-0234
- Status last verified
- Aug 2025
- First submitted
- 8 Jan 2024
- Last updated
- 26 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Feasibility Study of Amantadine for Cognitive Dysfunction in Patients With Long-Covid: A Pilot Randomized Control Trial
- ClinicalTrials.gov ID
- NCT06234462
- Acronym / sponsor ID
- STU-2023-0234
- Conditions
- Long COVID, Post-Acute COVID-19 Syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: challenges with recruitment
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Study start
- Jun 2025 (estimated)
- Primary completion
- 1 Sep 2025 (estimated)
- Study completion
- 1 Oct 2025 (estimated)
- First posted
- 31 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard of Care | Active comparator | Other: Physical, Occupational, Speech Therapy, Other: Provider Counseling, Other: Medications for symptoms managementParticipants 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 | Experimental | Drug: Amantadine, Other: Physical, Occupational, Speech Therapy, Other: Provider Counseling, Other: Medications for symptoms managementParticipants in this arm will review standard of care and amantadine. |
Who may qualify
- Ages
- 20 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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:
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AmantadineParticipants 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 | Drug | Standard of Care + Amantadine |
| Physical, Occupational, Speech TherapyPhysical 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 | Standard of Care, Standard of Care + Amantadine |
| Provider CounselingClinic providers will provide counseling/education on Long-COVID. | Other | Standard of Care, Standard of Care + Amantadine |
| Medications for symptoms managementClinic 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. | Other | Standard of Care, Standard of Care + Amantadine |
Primary outcome
Measures of cognitive functioning
Time frame: 4 weeks
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)
Measures of cognitive functioning
Time frame: 4 weeks
Cognitive Subscale of Modified Fatigue Impact Scale (MFIS)
Measures of cognitive functioning
Time frame: 4 weeks
Self-reported percent back to normal
Measures of cognitive functioning
Time frame: 4 weeks
FAS Test
Measures of cognitive functioning
Time frame: 4 weeks
Trails A \& B
Measures of cognitive functioning
Time frame: 4 weeks
Digit Vigilance Test
8 secondary outcomes
Measures of endurance and strength
Time frame: 4 weeks
Measures of endurance and strength
Time frame: 4 weeks
Measures of endurance and strength
Time frame: 4 weeks
Measures of endurance and strength
Time frame: 4 weeks
Measures of fatigue
Time frame: 4 weeks
Measures of anxiety and depression
Time frame: 4-6 weeks
Measures of anxiety and depression
Time frame: 4-6 weeks
Measures of anxiety and depression
Time frame: 4-6 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Aug 2025.
- Individual participant dataSharing planned: No
Related trials for Long COVID
Not yet recruitingPhase 1
Phase I Open-Label Safety Trial of Pembrolizumab for Neurological Post- Acute Sequelae of SARS-CoV-2 (PD1-PASC I)
Post-Acute COVID-19 Syndrome
Recruiting
Whole-body Cryotherapy in Those With Chronic Fatigue: A Feasibility Study
ME/CFS, Fibromyalgia (FM)
Not yet recruitingPhase 3
The Study of Brave-LC LDN Treatment Trial
Post-acute COVID-19 Syndrome
Active, not recruitingObservational study
Epigenetic Changes in Long COVID Patients
Long COVID-19 Syndrome, Long COVID Symptoms
Enrolling by invitationPhase 2
Immunotherapy for Neurological Post-Acute Sequelae of SARS-CoV-2
Systemic Inflammation, Neuroinflammation
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Amy Mathews, M.D. principal investigator
University of Texas Southwestern Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Amantadine, Physical, Occupational, Speech Therapy and Provider Counseling in people with Long COVID and Post-Acute COVID-19 Syndrome, run by University of Texas Southwestern Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 26 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Measures of cognitive functioning (time frame: 4 weeks). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Aug 2025.