Clinical trial NCT06821087: Evaluating the Neuromodulatory Effect of Ketamine in Long COVID-19
Official title: Evaluating the Neuromodulatory Effect of Ketamine in Long COVID: A Pilot Study Targeting Fatigue and Neurocognitive Symptoms
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE2
Conditions: Long COVID
Keywords: Long COVID
Post-COVID Condition
Post-Acute Sequelae of COVID-19
Brain Fog
Fatigue
Ketamine
Lead sponsor: University of Texas at Austin
Sponsor class: OTHER
Collaborators: name: Roots Behavioral Health
First posted: 2025-02-11
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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. Some 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, and for some, another 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.


Eligibility criteria: 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.

The first 5 male and first 5 female participants to enroll will be invited to participate in the MRI portion of the study, provided they have no contraindications to MRI on screening. If participants decline to participate in the MRI portion, it will be offered to subsequent participants upon enrollment, ensuring there is no gender imbalance greater than 6 to 4 for the MRI portion.

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

Note participants with contraindications to MRI imaging will be excluded from the subset of 10 patients undergoing that testing

Primary outcomes:
measure: PROMIS SF v1.0 - Fatigue 8a
timeFrame: At enrollment and at the post-treatment assessment visit, 6 weeks following completion of the ketamine treatment.
measure: PROMIS SF v2.0 Cognitive Function 4a
timeFrame: At enrollment and at the post-treatment assessment visit, 6 weeks following completion of the ketamine treatment.
measure: BrainCheck Cognitive Battery
timeFrame: At enrollment and at the post-treatment assessment visit, 6 weeks following completion of the ketamine treatment.
measure: Number of participants with treatment-related adverse events as assessed by standardized interview
timeFrame: 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 outcomes:
measure: PROMIS Global 10 v1.2
timeFrame: Collected at baseline (pre-treatment) and at the post-treatment assessment (6 weeks after the final ketamine session).
measure: NASA Task Load Index (NASA-TLX)
timeFrame: Collected at baseline (pre-treatment) and at the post-treatment assessment (6 weeks after the final ketamine session).
measure: Patient Health Questionnaire-9 (PHQ-9)
timeFrame: Collected before each ketamine treatment session, at baseline, and at the post-treatment assessment (6 weeks post-treatment).
measure: Generalized Anxiety Disorder-7 (GAD-7)
timeFrame: Collected before each ketamine treatment session, at baseline, and at the post-treatment assessment (6 weeks post-treatment).
measure: Depression in Medically Ill 10 Scale (DMI-10)
timeFrame: Collected at baseline (pre-treatment) and at the post-treatment assessment (6 weeks after the final ketamine session).
measure: Long COVID Review of Systems
timeFrame: Collected at baseline (pre-treatment) and at the post-treatment assessment (6 weeks after the final ketamine session).
measure: Neuroimaging (MRI) Outcomes
timeFrame: Performed at baseline and repeated at the post-treatment assessment (6 weeks after the final ketamine session) for participants in the imaging subgroup.
measure: Serum Biomarker Analysis
timeFrame: Collected at baseline and at the post-treatment assessment (6 weeks after the final ketamine session).
Other outcomes:
Locations:
city: Austin
country: United States
facility: UT Health Austin
state: Texas
Study officials:
affiliation: University of Texas at Austin
name: W. Michael Brode, MD
role: PRINCIPAL_INVESTIGATOR
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