Evaluating the Neuromodulatory Effect of Ketamine in Long COVID-19

April 27, 2026 updated by: William Michael Brode, University of Texas at Austin

Evaluating the Neuromodulatory Effect of Ketamine in Long COVID: A Pilot Study Targeting Fatigue and Neurocognitive Symptoms

Plain Language Summary:

This study is a clinical trial to see if ketamine can help treat symptoms of Long COVID, especially fatigue and problems with thinking clearly (often called "brain fog"). Long COVID is a condition that affects people even after they have recovered from COVID-19, causing ongoing health issues like tiredness, memory problems, and difficulty concentrating. Right now, there are very few treatments available for these symptoms, and many people are looking for new options to feel better.

What is the study trying to find out? Does ketamine help reduce fatigue and improve thinking skills in people with Long COVID? Does ketamine improve overall quality of life and mental health for people with Long COVID? Is ketamine safe and well-tolerated for people with Long COVID? How does ketamine affect the body's biological processes, like inflammation and brain function? How will the study work?

The study will include 20 adults between 18 and 65 years old who have Long COVID symptoms like fatigue or brain fog.

Participants will first meet with researchers to answer health questions, take surveys about their symptoms, and do tests to check their thinking skills. All participants will also have a brain scan (MRI) and give a blood sample to look at markers of inflammation.

Participants will then receive four ketamine treatments over two weeks at a specialized clinic. The ketamine will be given as an injection, with the dose slightly increasing during the treatment period.

After six weeks, participants will return for follow-up tests to see if their symptoms have improved. This includes repeating the surveys, thinking tests, MRI and blood test.

Why ketamine? Ketamine is a medicine originally used for anesthesia but has also been found to help with depression and other mental health issues. Researchers think it might help with Long COVID symptoms because it can reduce inflammation in the brain and improve how the brain functions. People with Long COVID often have signs of inflammation and changes in brain chemicals, which ketamine might help balance.

What are the potential benefits? Participants might experience less fatigue and clearer thinking after ketamine treatment. They could also feel better overall in terms of mood and quality of life. Since ketamine can work quickly, some people may notice improvements shortly after starting the treatment.

What are the risks? Ketamine can cause side effects like feeling dizzy, anxious, or having an unusual sense of reality (sometimes called dissociation). It may also cause temporary increases in blood pressure or heart rate. All treatments will be carefully monitored by healthcare professionals to ensure safety.

Who can participate? Adults aged 18-65 with Long COVID who have significant fatigue or thinking problems can join. People will not be able to participate if they have certain health conditions like severe heart disease, uncontrolled high blood pressure, or a history of severe mental health disorders.

Why is this study important? Long COVID affects millions of people, and many are struggling to find treatments that work. This study is one of the first to explore ketamine as a potential treatment for Long COVID symptoms. If ketamine helps, it could lead to more research and eventually new treatment options for people living with Long COVID.

Study Overview

Status

Enrolling by invitation

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

20

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Austin, Texas, United States, 78712
        • UT Health Austin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Adults aged 18-65 years diagnosed with LC and possess a documented history of positive COVID-19 diagnostic testing or a probable infection as determined by a healthcare provider.
  • One persistent symptom of fatigue or neurocognitive dysfunction as defined by rating their symptoms as moderate to severe on the screening form.
  • English as a primary language OR comprehension of English suitable to understand research staff instructions.
  • All participants must be eligible for MRI and will undergo MRI scans pre- and post-treatment

Exclusion Criteria:

Contraindications to ketamine therapy:

  • Current substance use disorder
  • Current mania or psychosis
  • Recent myocardial infarction or stroke (within 1 year)
  • Unstable cardiovascular disease (including uncontrolled high blood pressure > 180/110 mmHg)
  • Uncontrolled seizure disorder
  • Pregnancy

Additional exclusion criteria include:

  • Recent COVID-19 infection or reinfection within 8 weeks
  • Prior receipt of ketamine treatment

  • History of treatment resistant depression (TRD) prior to development of LC

    • Defined as completing a trial (2 months of treatment at highest tolerated dose) of 3 or more psychotropic medications from at least 2 classes of medications (i.e. SSRIs, SNRIs, antipsychotic medications, or mood stabilizers such as lithium, lamotrigine, Depakote, or oxcarbazepine)
    • Psychotropic medications used during treatment of LC will not be counted as medications used for TRD

  • Current severe depression or anxiety, and/or active suicidal ideation

    • Severe depression and anxiety defined as scoring > 19 on PHQ-9 screening or > 14 on GAD-7 screening.
    • Active suicidal ideation is defined as answering "yes" to question #9 on the PHQ-9
  • History of bipolar disorder, schizophrenia, or schizoaffective disorder
  • History of suicide attempt or psychiatric hospitalization for any reason in the last 5 years
  • Current benzodiazepine or naltrexone medication use within 4 weeks of enrollment as these may decrease or block the therapeutic effect of ketamine treatment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Ketamine Therapy
Participants in this arm will receive four intramuscular (IM) ketamine injections over a two-week period. The initial dose will be 0.5 mg/kg during the first session, increasing to 0.65 mg/kg in the second session, and 0.75 mg/kg for the third and fourth sessions. Injections will be administered at least three days apart. All treatments will be conducted under medical supervision at a specialized clinic with standard safety protocols in place. Vital signs will be monitored before, during, and after each session to assess tolerability. Participants will also undergo assessments of fatigue, cognitive function, quality of life, and biomarkers pre- and post-treatment. Participants will receive fMRI imaging pre- and post-treatment.
Drug: Ketamine only
Participants in this arm will receive four intramuscular (IM) ketamine injections over a two-week period. The initial dose will be 0.5 mg/kg during the first session, increasing to 0.65 mg/kg in the second session, and 0.75 mg/kg for the third and fourth sessions. Injections will be administered at least three days apart.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
PROMIS SF v1.0 - Fatigue 8a
Time Frame: At enrollment and at the post-treatment assessment visit, 6 weeks following completion of the ketamine treatment.
A patient-reported questionnaire measuring the severity and impact of fatigue on daily activities over the past 7 days. Higher scores indicate greater fatigue.
At enrollment and at the post-treatment assessment visit, 6 weeks following completion of the ketamine treatment.
PROMIS SF v2.0 Cognitive Function 4a
Time Frame: At enrollment and at the post-treatment assessment visit, 6 weeks following completion of the ketamine treatment.
A patient-reported tool that measures perceived cognitive abilities, such as memory, concentration, and mental clarity, over the past 7 days. Higher scores reflect better cognitive function.
At enrollment and at the post-treatment assessment visit, 6 weeks following completion of the ketamine treatment.
BrainCheck Cognitive Battery
Time Frame: At enrollment and at the post-treatment assessment visit, 6 weeks following completion of the ketamine treatment.
A computerized series of neuropsychological tests assessing objective cognitive functions, including memory, attention, executive function, processing speed, and response inhibition. Scores are age-normalized.
At enrollment and at the post-treatment assessment visit, 6 weeks following completion of the ketamine treatment.
Number of participants with treatment-related adverse events as assessed by standardized interview
Time Frame: Adverse events will be assessed at each of the four ketamine treatment sessions and during the final post-treatment assessment, which occurs six weeks after the last ketamine injection.
A standardized interview conducted post-treatment to identify and record any physical or psychological side effects experienced by participants during the ketamine therapy.
Adverse events will be assessed at each of the four ketamine treatment sessions and during the final post-treatment assessment, which occurs six weeks after the last ketamine injection.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
PROMIS Global 10 v1.2
Time Frame: Collected at baseline (pre-treatment) and at the post-treatment assessment (6 weeks after the final ketamine session).
A 10-item questionnaire assessing overall physical, mental, and social health, including pain, fatigue, and emotional well-being.
Collected at baseline (pre-treatment) and at the post-treatment assessment (6 weeks after the final ketamine session).
NASA Task Load Index (NASA-TLX)
Time Frame: Collected at baseline (pre-treatment) and at the post-treatment assessment (6 weeks after the final ketamine session).
A tool used to evaluate perceived mental workload, assessing factors like mental demand, effort, and frustration during cognitive tasks like BrainCheck.
Collected at baseline (pre-treatment) and at the post-treatment assessment (6 weeks after the final ketamine session).
Patient Health Questionnaire-9 (PHQ-9)
Time Frame: Collected before each ketamine treatment session, at baseline, and at the post-treatment assessment (6 weeks post-treatment).
A widely used self-report measure to assess the severity of depressive symptoms over the past two weeks.
Collected before each ketamine treatment session, at baseline, and at the post-treatment assessment (6 weeks post-treatment).
Generalized Anxiety Disorder-7 (GAD-7)
Time Frame: Collected before each ketamine treatment session, at baseline, and at the post-treatment assessment (6 weeks post-treatment).
A widely used 7-item scale measuring the severity of anxiety symptoms over the past two weeks.
Collected before each ketamine treatment session, at baseline, and at the post-treatment assessment (6 weeks post-treatment).
Depression in Medically Ill 10 Scale (DMI-10)
Time Frame: Collected at baseline (pre-treatment) and at the post-treatment assessment (6 weeks after the final ketamine session).
A measure designed to assess depressive symptoms specifically in individuals with medical conditions, focusing on somatic and cognitive symptoms.
Collected at baseline (pre-treatment) and at the post-treatment assessment (6 weeks after the final ketamine session).
Long COVID Review of Systems
Time Frame: Collected at baseline (pre-treatment) and at the post-treatment assessment (6 weeks after the final ketamine session).
A comprehensive symptom checklist adapted from the WHO's Global COVID-19 Clinical Platform, evaluating the range and severity of Long COVID symptoms.
Collected at baseline (pre-treatment) and at the post-treatment assessment (6 weeks after the final ketamine session).
Serum Biomarker Analysis
Time Frame: Collected at baseline and at the post-treatment assessment (6 weeks after the final ketamine session).
Blood samples will be analyzed for inflammatory and metabolic markers, including cytokines and metabolites in the kynurenine pathway, to assess biological responses to ketamine treatment.
Collected at baseline and at the post-treatment assessment (6 weeks after the final ketamine session).
Neuroimaging (MRI) Outcomes
Time Frame: Performed at baseline and repeated at the post-treatment assessment (6 weeks after the final ketamine session).
Functional MRI (fMRI) scans will evaluate changes in brain structure and connectivity, providing insight into the neurological effects and mechanisms of ketamine.
Performed at baseline and repeated at the post-treatment assessment (6 weeks after the final ketamine session).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Texas at Austin

Collaborators

Roots Behavioral Health

Investigators

  • Principal Investigator: W. Michael Brode, MD, University of Texas at Austin

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 28, 2025

Primary Completion (Estimated)

May 1, 2026

Study Completion (Estimated)

May 1, 2026

Study Registration Dates

First Submitted

February 10, 2025

First Submitted That Met QC Criteria

February 10, 2025

First Posted (Actual)

February 11, 2025

Study Record Updates

Last Update Posted (Actual)

April 28, 2026

Last Update Submitted That Met QC Criteria

April 27, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STUDY00006367

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Individual Participant Data (IPD) to be shared will include de-identified data related to primary and secondary outcomes, such as patient-reported outcomes (e.g., PROMIS Fatigue and Cognitive Function scores), objective cognitive assessments from the BrainCheck battery, and adverse event reports. Additionally, de-identified neuroimaging data (for participants undergoing MRI) and biomarker data from blood samples will be included. Only data used in the results publication and relevant to the study's primary and secondary outcomes will be shared. All shared data will be stripped of personal identifiers to maintain participant confidentiality, following HIPAA guidelines.

IPD Sharing Time Frame

The de-identified IPD will be made available beginning 6 months after publication of the primary study results. Data will be available for a period of 3 years following this initial release.

IPD Sharing Access Criteria

Data will be shared with qualified researchers affiliated with academic institutions, healthcare organizations, or other research entities conducting studies related to Long COVID, neurocognitive function, or ketamine treatment. Researchers must submit a formal data request, including a summary of the proposed research and intended use of the data. Requests will be reviewed by the study's principal investigator and research team to ensure alignment with ethical guidelines and scientific merit. Approved researchers will be required to sign a data use agreement to ensure proper handling and confidentiality of the data.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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