Ketamine for Post-COVID Syndrome

Overseen By Kristina Kashyap

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Texas at Austin

Must not be taking: Benzodiazepines, Naltrexone

Disqualifiers: Substance use, Mania, Psychosis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

Duration: 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether ketamine, an anesthetic, can alleviate Long COVID symptoms such as fatigue and brain fog. Long COVID affects individuals even after recovering from COVID-19, leading to persistent tiredness and memory issues. The trial aims to determine if ketamine can reduce these symptoms and enhance overall quality of life by assessing its impact on brain function and inflammation. Adults with Long COVID experiencing significant fatigue or cognitive issues may qualify, provided they do not have certain other health conditions like severe heart disease or mental health disorders. As a Phase 2 trial, this research measures ketamine's effectiveness in an initial, smaller group, offering a potential improvement in quality of life.

Do I need to stop my current medications to join the trial?

Yes, you will need to stop taking benzodiazepines or naltrexone at least 4 weeks before enrolling in the trial, as these medications may interfere with the effects of ketamine.

Is there any evidence suggesting that ketamine is likely to be safe for humans?

Research has shown that ketamine is generally safe and well-tolerated under medical supervision. In studies where ketamine was used for conditions like depression, participants experienced side effects such as dizziness, anxiety, and a temporary feeling of disconnection from reality. These effects typically occur soon after taking the drug and often resolve quickly.

Some studies found that ketamine can temporarily raise blood pressure or heart rate. Healthcare professionals monitor and manage these changes during treatment. While short-term use of ketamine has been studied, less information exists about its long-term safety, especially with repeated doses.

The FDA has already approved ketamine for use as an anesthetic, indicating a known safety profile when used correctly. However, more research is needed specifically for its use in Long COVID. This study will closely monitor participants to ensure their safety throughout the treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Long COVID?

Unlike the standard treatments for post-COVID syndrome, which typically involve symptom management with medications like steroids, antivirals, or physical therapy, ketamine offers a unique approach. Ketamine is believed to work by modulating glutamate, a neurotransmitter in the brain, potentially addressing both physical and mental health aspects of post-COVID syndrome. Researchers are excited about ketamine because it might provide rapid relief from symptoms like fatigue and cognitive issues, and it could improve quality of life more quickly than traditional therapies. Additionally, its administration through intramuscular injections under medical supervision ensures both safety and precise dosing.

What evidence suggests that ketamine might be an effective treatment for Long COVID?

Studies have shown that ketamine might help with symptoms of Long COVID, such as tiredness and difficulty thinking clearly. This trial will administer ketamine therapy to participants to evaluate its effects on these symptoms. Ketamine reduces brain swelling and improves brain function, which could address some changes seen in Long COVID. Evidence from other conditions, like depression, suggests ketamine can quickly boost mood and clear thinking. One case report indicated that ketamine helped with tiredness after COVID, showing promise for its effectiveness. While more research is needed, these early findings offer hope that ketamine could be a helpful treatment for those dealing with Long COVID symptoms. ^{1 5 6 7 8}

Who Is on the Research Team?

W. Michael Brode, MD

Principal Investigator

University of Texas at Austin

Are You a Good Fit for This Trial?

Adults aged 18-65 with Long COVID, experiencing significant fatigue or thinking problems, can join this trial. They must have had a positive COVID-19 test or probable infection and be able to understand English. Those with severe heart issues, uncontrolled high blood pressure, or serious mental health disorders cannot participate.

Inclusion Criteria

English as a primary language OR comprehension of English suitable to understand research staff instructions

I am one of the first 5 men/women enrolled and can have an MRI.

I am between 18-65 years old, have lung cancer, and had COVID-19.

Exclusion Criteria

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Treatment

Participants receive four ketamine treatments over two weeks, with doses increasing from 0.5 mg/kg to 0.75 mg/kg

2 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including surveys, cognitive tests, and for some, MRI and blood tests

6 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Ketamine

Trial Overview

The study is testing if ketamine injections can reduce fatigue and improve cognitive function in Long COVID patients. Over two weeks, participants will receive four increasing doses of ketamine at a clinic. Follow-up tests after six weeks will check for symptom improvements.

How Is the Trial Designed?

Group I: Ketamine Therapy Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

University of Texas at Austin

Lead Sponsor

Trials

387

Recruited

86,100+

Roots Behavioral Health

Collaborator

Trials

1

Recruited

20+

Published Research Related to This Trial

In a systematic review of 93 studies involving 3756 participants receiving sub-anesthetic doses of ketamine for psychiatric disorders, only four serious adverse medical events (MSAEs) were reported, resulting in an incidence of approximately 0.1%, indicating a very low risk of serious complications.

No serious cardiac events or deaths were observed, and most studies effectively screened out high-risk patients, suggesting that with proper medical screening, ketamine can be administered safely for psychiatric treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review of the incidence of medical serious adverse events in sub-anesthetic ketamine treatment of psychiatric disorders. Hovda, N., Gerrish, W., Frizzell, W., et al.[2023]

This systematic review analyzed 60 studies on the safety of ketamine for treating depression, revealing that acute doses of ketamine led to more frequent side effects, including psychiatric and cardiovascular issues, compared to placebo.

There is a notable lack of data on the long-term safety and effects of repeated ketamine dosing, highlighting the need for large-scale clinical trials to better understand its safety profile over extended use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Side-effects associated with ketamine use in depression: a systematic review. Short, B., Fong, J., Galvez, V., et al.[2019]

Ketamine and esketamine demonstrate rapid antidepressant effects, with improvements in clinical response observed within 40 minutes to 1 week for ketamine and 2 hours to 4 weeks for esketamine, along with reductions in depression scores and suicidality.

Despite their effectiveness, the long-term safety and efficacy of ketamine and esketamine remain uncertain, and the overall quality of the studies reviewed was critically low, highlighting the need for more rigorous research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of ketamine and esketamine for depression: an overview of systematic reviews with meta-analyses. Lima, TM., Visacri, MB., Aguiar, PM.[2022]

A review of 34 articles revealed 312 cases of overdose and 138 deaths related to ketamine use, primarily in recreational settings and often involving polydrug use, highlighting significant risks associated with misuse.

Despite concerns about ketamine's safety in non-medical contexts, no overdoses or deaths were reported from its use as an antidepressant in therapeutic settings, suggesting it can be safely prescribed when used appropriately.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overdoses and deaths related to the use of ketamine and its analogues: a systematic review. Chaves, TV., Wilffert, B., Sanchez, ZM.[2023]

In a study involving 6630 patients treated with repeated parenteral ketamine for depression, only 0.7% experienced adverse effects that required discontinuation, indicating a high safety profile for this treatment.

Among published reports, the rate of significant adverse events leading to treatment discontinuation was low at 1.2%, suggesting that long-term ketamine treatment for depression is reasonably safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Repeated Administration of Parenteral Ketamine for Depression. Feifel, D., Dadiomov, D., C Lee, K.[2020]

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Neuropsychiatric manifestations related to COVID‐19 in 22% of patients, including anxiety, depression, mood disorders, and psychosis.

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IV Ketamine Therapy for Long COVID

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Ketamine, given mainly IV or parenterally, is a unique and safe drug that enables well-controlled, dose-dependent and timely calculated sedation, analgesia and ...