Ketamine for Depression and PTSD

Overseen By Mike Mallin, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: TruDiagnostic

Must not be taking: Ketamine, PCP, others

Disqualifiers: Dementia, Cardiovascular disease, Psychotic disorder, Substance use, 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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 2-3 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how ketamine, a type of medication, affects DNA-level aging in people with Major Depressive Disorder (MDD) or Post-Traumatic Stress Disorder (PTSD). The researchers aim to determine if ketamine can alter the rate of epigenetic aging (how old the body appears at a cellular level) using a specific test. Participants will receive a series of ketamine infusions over two to three weeks. Suitable candidates for the trial include those who have had MDD or PTSD for over four weeks, have tried medication without success, and can travel to the treatment location. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

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

The trial protocol does not specify if you need to stop your current medications, but it does exclude those who require medications that interact with ketamine. It's best to discuss your current medications with the trial team.

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

Research has shown that ketamine is generally safe for treatment, though it can have some side effects. The FDA has already approved ketamine as a general anesthetic, indicating a well-understood safety profile, which is promising for its use in other treatments.

In studies, about 12% of participants experienced "emergence reactions" after taking ketamine. These reactions can range from pleasant to slightly unsettling, such as feeling dreamy or confused. Typically, these effects are short-lived and resolve on their own.

Other possible side effects include changes in heart rate and blood pressure, as well as irritation if it contacts the eyes or skin. These effects are common with anesthetics and are managed by healthcare professionals during treatment.

Before starting any treatment, discussing all potential risks and benefits with a healthcare provider is important. They can help determine if ketamine is the right choice for a specific condition. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for MDD or PTSD?

Most treatments for mental health conditions such as depression typically involve antidepressants or psychotherapy, which can take weeks to show results. But ketamine offers something different and exciting. Unlike standard options, ketamine is administered through subanesthetic infusion and acts rapidly, often bringing relief within hours or days. Researchers are particularly interested in ketamine's unique mechanism of action, which involves modulating the brain's NMDA receptors, potentially leading to faster and more effective treatment outcomes. This makes ketamine a promising alternative for those who do not respond well to traditional therapies.

What evidence suggests that ketamine might be an effective treatment for MDD or PTSD?

Research has shown that ketamine can help treat Major Depressive Disorder (MDD) and Post Traumatic Stress Disorder (PTSD). One study found that a single, low-dose ketamine infusion quickly reduced depression symptoms in some patients within hours. Another study showed that 91% of patients experienced positive effects from ketamine treatment for up to four weeks. In this trial, participants will receive subanesthetic ketamine infusions over 2-3 weeks. Receiving ketamine infusions over several days has also reduced depression, anxiety, and pain in patients with ongoing issues. These findings suggest ketamine could be a promising option for those with MDD or PTSD. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

Inclusion Criteria

Read, understand, and provide written informed consent in English

Have a history of at least 1 failed medication trial targeting MDD or PTSD

Be generally healthy, as assessed by medical history, physical examination (including vital signs), and clinical laboratory evaluations

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Subjects receive a series of six ketamine infusions over two to three weeks

2-3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ketamine

How Is the Trial Designed?

Group I: Ketamine Infusion Experimental Treatment 1 Intervention

subanesthetic ketamine infusion (0.5mg/kg) over 2-3 weeks

Ketamine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Ketalar for:

• Anesthesia
• Treatment-resistant depression

Approved in European Union as Ketalar for:

• Anesthesia
• Treatment-resistant depression

Approved in United States as Spravato for:

• Treatment-resistant depression

Approved in European Union as Spravato for:

• Treatment-resistant depression

Approved in Canada as Spravato for:

• Treatment-resistant depression

Who Is Running the Clinical Trial?

TruDiagnostic

Lead Sponsor

Trials

12

Recruited

490+

Founded

2019

Headquarters

Lexington, United States

Known For

Epigenetic testing

Wild Health

Collaborator

Trials

1

Recruited

20+

Published Research Related to This Trial

In a study involving 9 children with refractory convulsive status epilepticus (RSE), intravenous ketamine was found to be effective in resolving RSE in 6 of the patients, demonstrating its potential as a treatment option.

The treatment was deemed safe, as none of the patients experienced serious adverse events, suggesting that ketamine could be a viable alternative for children who do not respond to conventional anesthetics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of ketamine in refractory status epilepticus in children. Rosati, A., L'Erario, M., Ilvento, L., et al.[2022]

A new method using gas chromatography-mass spectrometry (GC-MS) allows for the sensitive detection and measurement of ketamine and its metabolite norketamine in hair samples, with a quantitation limit of 0.05 ng/mg.

In an experiment with 15 cavies, it was found that the concentration of ketamine in hair is directly related to the dosage administered, with higher concentrations observed in black hair compared to brown and white hair, indicating that hair color may influence drug incorporation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hair analysis for ketamine and its metabolites. Xiang, P., Shen, M., Zhuo, X.[2016]

A new subcutaneous formulation of ketamine was developed using Captisol® to achieve a balanced pH and osmolality close to physiological levels, which may reduce injection site irritation and sterile abscesses commonly seen with current formulations.

This innovative formulation strategy allows for a buffered ketamine solution that maintains high concentration while minimizing adverse reactions, suggesting potential for broader application in other amine-based medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three Birds, One Excipient: Development of an Improved pH, Isotonic, and Buffered Ketamine Formulation for Subcutaneous Injection. Wallach, J., Gamrat, J., Jauhola-Straight, R., et al.[2022]

A review of 41 treatment arms from 21 studies found that ketamine formulations that maximize first pass metabolism and delay the time to peak concentration (Tmax) are associated with better safety and tolerability, particularly in reducing side effects like dissociation and increased blood pressure.

The study revealed strong correlations between the ketamine:norketamine ratio and both dissociation ratings and blood pressure changes, suggesting that careful formulation can help minimize adverse effects while maintaining the antidepressant efficacy of ketamine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of formulation and route of administration on ketamine's safety and tolerability: systematic review. Glue, P., Russell, B., Medlicott, NJ.[2021]

In a European clinical trial, a 55-year-old male with treatment-resistant depression and substance use disorder showed significant improvement in depression symptoms after a single intravenous infusion of ketamine, with reductions in Hamilton Depression Rating Scale (HDRS) scores from 36 to 16 and Beck Depression Inventory (BDI) scores from 26 to 9.

The antidepressant effects of ketamine were rapid, with the patient reporting improvements just 25 minutes into the infusion, and these effects lasted for at least 7 days, demonstrating ketamine's potential as a fast-acting treatment for depression even in patients with co-occurring substance use disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous ketamine therapy in a patient with a treatment-resistant major depression. Liebrenz, M., Borgeat, A., Leisinger, R., et al.[2022]

A systematic review of 19 studies involving 1006 patients found that combining psychotherapy with ketamine treatment for psychiatric disorders generally leads to positive outcomes, particularly for conditions like substance use disorders and treatment-resistant depression.

Despite the promising results, the significant variability in psychotherapy types and ketamine protocols across studies means that more standardized and larger randomized controlled trials are needed to determine the best ways to integrate these treatments effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine and psychotherapy for the treatment of psychiatric disorders: systematic review. Kew, BM., Porter, RJ., Douglas, KM., et al.[2023]

A 49-year-old woman with severe treatment-resistant major depression experienced significant improvement after receiving 36 sessions of ketamine intravenous therapy over 10 months, resulting in nearly a 50% reduction in her depressive symptoms.

The case suggests that long-term repeated ketamine therapy could be a viable option for patients with treatment-resistant depression, but further research is needed to determine the best treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous ketamine infusion for a patient with treatment-resistant major depression: a 10-month follow-up. Kwon, JH., Sim, WS., Hong, JP., et al.[2018]

Oral ketamine is a potentially safe and effective treatment for depression, but it requires higher doses (2.0-2.5 mg/kg) compared to intravenous administration due to lower systemic absorption (20%-25%).

Despite its promise as a more accessible and affordable option for treatment, the current literature on oral ketamine is limited, and further research is needed to understand its pharmacokinetics, safety, and efficacy compared to other administration routes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral Ketamine for Depression, 2: Practical Considerations. Andrade, C.[2020]

There is currently no standardized safety monitoring protocol for off-label use of generic ketamine, and safety monitoring for intranasal esketamine varies by jurisdiction, leading to potential gaps in patient safety.

The Ketamine Side Effect Tool (KSET) is recommended as a comprehensive tool for monitoring both acute and long-term side effects of ketamine and esketamine treatments, addressing the lack of agreed frameworks for safety monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Ketamine Side Effect Tool (KSET): A comprehensive measurement-based safety tool for ketamine treatment in psychiatry. Bayes, A., Short, B., Zarate, CA., et al.[2023]

Subcutaneous (SC) administration of racemic ketamine and esketamine has shown rapid and robust antidepressant effects in both unipolar and bipolar patients, with response and remission rates ranging from 50% to 100% after single or multiple doses.

The studies indicated that SC ketamine is generally well-tolerated, with only transitory side effects, making it a promising and cost-effective treatment option for depression, especially in developing countries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous Ketamine in Depression: A Systematic Review. Cavenaghi, VB., da Costa, LP., Lacerda, ALT., et al.[2021]

In a study of 9016 patients receiving ketamine intravenous therapy (KIT) for depression, 53.6% showed a significant response (≥50% reduction in depression scores) within 14-31 days, indicating KIT's efficacy in real-world settings.

While most patients benefited from KIT, a small percentage (8.4%) experienced worsening depressive symptoms, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective analysis of ketamine intravenous therapy for depression in real-world care settings. McInnes, LA., Qian, JJ., Gargeya, RS., et al.[2023]

Citations

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Conclusion: Multiday subanesthetic ketamine infusions effectively reduce pain, anxiety and depression in patients with complex chronic pain. Plain language ...

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Ketamine treatment for depression: a review - PMC

A single, subanesthetic-dose IV ketamine infusion was shown to rapidly and effectively reduce suicidal ideation in controlled trials of TRD ...

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sciencedirect.com

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Real World Effectiveness of Maintenance Ketamine ...

91% of 23 patients had shown sustained response over 4 weeks of maintenance treatment [Phillips et al., 2019]. An additional naturalistic follow ...

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medrxiv.org

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Effectiveness of continuous Ketamine infusion associated ...

This study aims to evaluate the effectiveness of continuous four days of Ketamine infusion associated with magnesium sulfate for inpatients.

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A randomized, double-blind, active placebo-controlled ...

Single ketamine at subanesthetic dose of 0.5 mg/kg for 40 min has demonstrated improvement in mood within a few hours in some patients with ...

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Ketamine - StatPearls - NCBI Bookshelf - NIH

Ketamine is a medication approved by the United States Food and Drug Administration (FDA) for use as a general anesthetic either on its own or in combination ...

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accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2012/016812s039lbl.pdf

Ketalar Label - accessdata.fda.gov

SPECIAL NOTE. EMERGENCE REACTIONS HAVE OCCURRED IN APPROXIMATELY 12 PERCENT OF PATIENTS. THE PSYCHOLOGICAL MANIFESTATIONS VARY IN SEVERITY BETWEEN PLEASANT ...

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northamerica.covetrus.com

northamerica.covetrus.com/Content/pdfs/P010177.pdf

SAFETY DATA SHEET

Other Hazards. Short Term: Anesthetic drug: may cause central nervous system and cardiovascular system May cause eye irritation. May be harmful if absorbed ...

9.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2017/016812s043lbl.pdf

KETALAR (ketamine hydrochloride) injection

Since the safe use in pregnancy, including obstetrics (either vaginal or abdominal delivery), has not been established, such use is not recommended (see ANIMAL ...

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research.fiu.edu

research.fiu.edu/documents/facilities/acf/documents/Ketamine.pdf

Material Safety Data Sheet

Flush skin with plenty of soap and water for at least 15 minutes (remove all contaminated clothing and shoes). Get medical attention.