Ketamine and Epigenetic Aging

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

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing ketamine infusions to help people with depression or PTSD. The treatment involves multiple sessions over a short period. Ketamine may improve mood by changing how brain cells communicate. Ketamine has been shown to have rapid and robust effects on depression, with improvements often seen immediately after administration and lasting for a significant duration.

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.

What evidence supports the effectiveness of the drug ketamine for treating depression?

Research shows that ketamine, when given intravenously, can quickly improve symptoms in people with severe depression, especially those who haven't responded to other treatments. It has been found effective in both short-term and long-term use for depression. ^{1 2 3 4 5}

Is ketamine generally safe for human use?

Ketamine has been used in various medical treatments, including depression and pain management. Common side effects include a sense of detachment from reality and increased blood pressure. While it shows promise in treating certain conditions, it can cause temporary side effects, and its safety can depend on the formulation and method of administration. ^{6 7 8 9 10}

How does the drug ketamine differ from other treatments for its condition?

Ketamine is unique because it works on multiple receptors in the brain, including NMDA receptors, which makes it effective for conditions like depression and pain. Unlike many other treatments, it can be administered in various ways, such as intravenously, and even in low doses, it provides pain relief. Its rapid action and ability to work in patients with cardiovascular instability make it stand out from other options. ^{11 12 13 14 15}

Eligibility Criteria

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

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

Treatment Details

Interventions

• Ketamine

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

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

A retrospective analysis of ketamine intravenous therapy for depression in real-world care settings. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Intravenous ketamine therapy in a patient with a treatment-resistant major depression. [2022]

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

Ketamine and psychotherapy for the treatment of psychiatric disorders: systematic review. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Intravenous ketamine infusion for a patient with treatment-resistant major depression: a 10-month follow-up. [2018]

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

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

6. Switzerland pubmed.ncbi.nlm.nih.gov

Three Birds, One Excipient: Development of an Improved pH, Isotonic, and Buffered Ketamine Formulation for Subcutaneous Injection. [2022]

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

Efficacy and safety of ketamine in refractory status epilepticus in children. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

The Ketamine Side Effect Tool (KSET): A comprehensive measurement-based safety tool for ketamine treatment in psychiatry. [2023]

9. Germany pubmed.ncbi.nlm.nih.gov

Influence of formulation and route of administration on ketamine's safety and tolerability: systematic review. [2021]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Subcutaneous Ketamine in Depression: A Systematic Review. [2021]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Targeted mass spectrometry of ketamine and its metabolites cis-6-hydroxynorketamine and norketamine in human blood serum. [2021]

12. Korea (South) pubmed.ncbi.nlm.nih.gov

Ketamine anaesthesia following premedication of rabbits with vitamin C. [2013]

13. Germany pubmed.ncbi.nlm.nih.gov

Ketamine. [2017]

14. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[The influence of modulators of enzyme activity on the pharmacological effect of thiopental sodium and ketamine and on the pharmacokinetics of thiopental sodium]. [2017]

15. Ireland pubmed.ncbi.nlm.nih.gov

Hair analysis for ketamine and its metabolites. [2016]