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

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

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 ketamine safe for use in humans?

Ketamine is generally considered safe when used in a medical setting, with low rates of serious side effects reported in studies for conditions like depression. Most adverse effects are mild, and serious issues are rare, especially compared to recreational use, which carries higher risks. ^{1 2 3 4 5}

How does the drug ketamine differ from other treatments for post-COVID syndrome?

Ketamine is unique because it can rapidly improve severe depression and suicidal thoughts, which are common after COVID-19, and it also helps with sedation in critically ill patients. Unlike traditional antidepressants, ketamine works quickly and can be administered intravenously, making it a valuable option when fast action is needed. ^{6 7 8 9 10}

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. A subset of 10 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]

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]

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]

Citations

1. Netherlands pubmed.ncbi.nlm.nih.gov

A systematic review of the incidence of medical serious adverse events in sub-anesthetic ketamine treatment of psychiatric disorders. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Side-effects associated with ketamine use in depression: a systematic review. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Overdoses and deaths related to the use of ketamine and its analogues: a systematic review. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Safety of Repeated Administration of Parenteral Ketamine for Depression. [2020]

5. Germany pubmed.ncbi.nlm.nih.gov

Use of ketamine and esketamine for depression: an overview of systematic reviews with meta-analyses. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Observational study of the effect of ketamine infusions on sedation depth, inflammation, and clinical outcomes in mechanically ventilated patients with SARS-CoV-2. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

The Therapeutic Effects of Ketamine in Mental Health Disorders: A Narrative Review. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Uncovering the Benefits of the Ketamine-Dexmedetomidine Combination for Procedural Sedation during the Italian COVID-19 Pandemic. [2023]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Successful use of ketamine to treat severe depression with suicidality post-COVID-19 - A case report. [2023]

10. Ireland pubmed.ncbi.nlm.nih.gov

Real-world effectiveness of repeated ketamine infusions for treatment resistant depression during the COVID-19 pandemic. [2022]