Ketamine + Cognitive Behavioral Therapy for Neuropathic Pain

(PSYKED-NP Trial)

Overseen By Janneth Pazmino-Canizares, MSc

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Akash Goel

Must not be taking: Theophylline, Aminophylline, others

Disqualifiers: Schizophrenia, Bipolar, Hypertension, 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: Unknown

Duration: 20 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new methods to reduce chronic nerve pain using ketamine (a medication), cognitive behavioral therapy (a talking therapy), or a combination of both. The goal is to determine which treatment best eases pain. Individuals with moderate to severe chronic neuropathic pain (pain caused by nerve damage) who can give consent may be suitable for this study. Participants will be randomly assigned to one of the three treatment options to test their effectiveness. As a Phase 4 trial, the treatments are already FDA-approved and proven effective, aiming to understand how they benefit more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently using theophylline or aminophylline, or if you have used certain substances like amphetamines, alcohol, or ketamine in the past 6 months.

What is the safety track record for these treatments?

Research has shown that ketamine is generally safe for treating long-term pain. Studies have found that small doses of ketamine provide strong pain relief by blocking certain signals in the brain. These small doses are safer than when ketamine is used as a full anesthetic, making serious side effects less likely.

The FDA has approved ketamine for other uses, indicating its general safety. Even accidental overdoses have been managed safely in the past. However, ketamine can still affect the brain, nerves, and heart, so careful use is essential.

Previous studies have safely combined ketamine with Cognitive Behavioral Therapy (CBT). This combination is being explored for its potential to enhance pain relief. Overall, current evidence supports the safety of using ketamine alone or with CBT, especially at low doses for chronic pain. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments for neuropathic pain because they offer a potentially groundbreaking approach. Unlike standard treatments like antidepressants, anticonvulsants, or opioids, which can take weeks to show effects, ketamine has the potential to provide rapid pain relief by targeting NMDA receptors in the brain. Additionally, combining ketamine with cognitive behavioral therapy (CBT) could enhance and prolong pain relief by addressing both the physical and psychological aspects of pain. This dual approach not only targets the pain directly but also empowers patients with coping strategies, making it a comprehensive treatment option.

What evidence suggests that this trial's treatments could be effective for neuropathic pain?

Research has shown that ketamine, one of the treatments in this trial, can greatly reduce pain in people with long-term nerve pain. It has provided lasting pain relief, especially when the pain involves nerve damage. Ketamine works well for about 44% of patients and somewhat helps another 20%.

This trial will also explore the effects of Cognitive Behavioral Therapy (CBT) as a separate treatment arm. Evidence suggests that when ketamine is used with CBT, the pain relief may last longer. Combining these two treatments, as tested in another arm of this trial, could improve pain management and enhance quality of life. Studies are examining how this combination can help, and early results are promising. ^{1 5 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with moderate-to-severe chronic neuropathic pain, as confirmed by a specialist and specific pain scores. Participants must be able to consent and if of childbearing potential, use effective contraception or practice abstinence.

Inclusion Criteria

I understand and can agree to the study's procedures and risks.

I have chronic nerve pain rated above 3 out of 10 in the last week.

I use effective birth control or practice abstinence as my usual lifestyle.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either Ketamine, psychotherapy, or a combination of both

20 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cognitive Behavioral Therapy
• Ketamine Hydrochloride

Trial Overview The study tests three approaches: Ketamine Hydrochloride alone, Cognitive Behavioral Therapy (CBT) alone, and a combination of both. The goal is to see which method best alleviates chronic neuropathic pain in this pilot study with 60 participants.

How Is the Trial Designed?

Group I: Ketamine + Psychotherapy Experimental Treatment 1 Intervention

Group II: Ketamine only Active Control 1 Intervention

Group III: Psychotherapy only Active Control 1 Intervention

Cognitive Behavioral Therapy is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Cognitive Behavioral Therapy for:

• Anxiety disorders
• Depressive disorders
• Eating disorders
• Post-traumatic stress disorder (PTSD)
• Obsessive-compulsive disorder (OCD)

Approved in United States as Cognitive Behavioral Therapy for:

• Anxiety disorders
• Depressive disorders
• Eating disorders
• Post-traumatic stress disorder (PTSD)
• Obsessive-compulsive disorder (OCD)
• Substance use disorders

Approved in Canada as Cognitive Behavioral Therapy for:

• Anxiety disorders
• Depressive disorders
• Eating disorders
• Post-traumatic stress disorder (PTSD)
• Obsessive-compulsive disorder (OCD)

Who Is Running the Clinical Trial?

Akash Goel

Lead Sponsor

Trials

1

Recruited

30+

Unity Health Toronto

Lead Sponsor

Trials

572

Recruited

470,000+

Published Research Related to This Trial

Ketamine shows moderate to weak evidence for efficacy in managing chronic pain, with level II evidence supporting its use for conditions like fibromyalgia and ischemic pain, while also being considered a 'third line' option when standard treatments fail.

For specific pain conditions such as phantom limb pain and postherpetic neuralgia, ketamine has demonstrated substantial pain relief, indicating its potential as an effective treatment in certain cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine in chronic pain management: an evidence-based review. Hocking, G., Cousins, MJ.[2022]

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]

This study is investigating the safety and feasibility of intranasal ketamine for treating uncontrolled cancer pain, with initial results from 7 subjects indicating potential for effective pain management without the harmful side effects associated with opioids.

If successful, intranasal ketamine could offer a non-opioid alternative for cancer pain relief, improving patients' quality of life while avoiding issues like respiratory depression and constipation that are common with opioid use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Intranasal Ketamine for Reducing Uncontrolled Cancer-Related Pain: Protocol of a Phase I/II Clinical Trial. Shteamer, JW., Harvey, RD., Spektor, B., et al.[2020]

Ketamine has been found to be an effective treatment for chronic pain conditions, including cancer-related neuropathic pain, and can help reduce the need for opioids by counteracting opioid-induced hyperalgesia.

At sub-anesthetic doses, ketamine demonstrates a significantly improved safety profile and fewer adverse events compared to its use as an anesthetic, making it a promising option for pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine Use for Cancer and Chronic Pain Management. Culp, C., Kim, HK., Abdi, S.[2021]

A patient with cancer-related neuropathic pain, unresponsive to standard treatments, was successfully treated with intrathecal administration of S(+)-ketamine alongside morphine, indicating its potential as an effective pain management option.

The continuous administration of S(+)-ketamine over 3 months resulted in low plasma levels and no significant side effects, suggesting a favorable safety profile for this treatment method.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term intrathecal S(+)-ketamine in a patient with cancer-related neuropathic pain. Benrath, J., Scharbert, G., Gustorff, B., et al.[2018]

In a study involving 20 patients with neuropathic pain, ketamine did not significantly reduce pain intensity compared to placebo over a 35-day period, indicating it may not provide long-term pain relief in this context.

The combination of ketamine with magnesium sulfate also showed no added benefit for pain relief or cognitive-emotional improvement, and the incidence of adverse events was relatively low across all treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine and Magnesium for Refractory Neuropathic Pain: A Randomized, Double-blind, Crossover Trial. Pickering, G., Pereira, B., Morel, V., et al.[2020]

Adding ketamine to standard treatment for neuropathic pain significantly reduces pain intensity both one week and 30 days after treatment, based on a meta-analysis of 18 randomized controlled trials with 706 participants.

While ketamine effectively alleviates pain, it also increases the risk of adverse effects, particularly psychedelic experiences, highlighting the need for careful consideration of its use in pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Ketamine in the Treatment of Neuropathic Pain: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Guimarães Pereira, JE., Ferreira Gomes Pereira, L., Mercante Linhares, R., et al.[2022]

Cognitive Behavioral Therapy (CBT) shows potential benefits for managing neuropathic pain, particularly in migraine patients, but the overall evidence is limited and of low methodological quality, with only 2 out of 34 systematic reviews rated as 'high' quality.

The study highlights the need for more rigorous research and improved methodologies in future systematic reviews to better assess the efficacy of different CBT formats for neuropathic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence Mapping Based on Systematic Reviews of Cognitive Behavioral Therapy for Neuropathic Pain. Li, C., Hou, W., Ding, D., et al.[2023]

In a study of 21 patients with chronic neuropathic pain, only 14% (3 patients) experienced an additional analgesic effect from oral ketamine, indicating limited efficacy for this treatment.

Adverse effects, such as dizziness and drowsiness, were significant, leading to almost half of the participants not progressing to the next phase of the trial, highlighting safety concerns with oral ketamine use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

N of 1 randomised controlled trials of oral ketamine in patients with chronic pain. Haines, DR., Gaines, SP.[2019]

Ketamine, traditionally used as an anesthetic, has shown effectiveness in treating chronic neuropathic pain, particularly in a patient with pain from cauda equina trauma, suggesting its potential as a pain management option.

The case report highlights the importance of using haloperidol to mitigate ketamine's psychomimetic side effects and suggests that oral administration may require lower doses and result in fewer side effects, indicating a need for further research on monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analgesic effect of oral ketamine in chronic neuropathic pain of spinal origin: a case report. Fisher, K., Hagen, NA.[2019]

A pediatric patient with chronic neuropathic pain and suicidality was successfully treated with subanesthetic intravenous ketamine infusion, highlighting its potential efficacy in managing both pain and depressive symptoms.

This case adds to the emerging evidence supporting ketamine as a treatment option for refractory pain and depression, particularly in challenging cases where traditional therapies may not be effective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case Report of Subanesthetic Intravenous Ketamine Infusion for the Treatment of Neuropathic Pain and Depression with Suicidal Features in a Pediatric Patient. Weber, G., Yao, J., Binns, S., et al.[2020]

Ketamine, when used in subanesthetic doses, has shown effectiveness in treating various types of neuropathic pain, including postherpetic neuralgia and cancer pain.

The review discusses different methods of administering ketamine, highlighting its potential for both central and peripheral pain management, which could offer new options for patients suffering from chronic pain conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic administration of ketamine for analgesia. Ben-Ari, A., Lewis, MC., Davidson, E.[2013]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9007468/

Efficacy and Safety of Ketamine in the Treatment of ... There is a statistically significant pain reduction by adding ketamine to the treatment of chronic NP when compared to the standard treatment.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4014022/

Ketamine for chronic pain: risks and benefits - PMC There is evidence that long term treatment of chronic pain (particularly in pain with a neuropathic component) with ketamine will cause prolonged pain relief, ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01951911

Effectiveness of Ketamine in Malignant Neuropathic Pain ... Study Overview​​ To see whether the addition of low-dose ketamine to a subcutaneous morphine infusion improves analgesia in patients with neuropathic cancer pain.

4. dig.pharmacy.uic.edu dig.pharmacy.uic.edu/faqs/2022-2/july-2022-faqs/what-is-the-role-of-oral-ketamine-in-pain-management/

What is the role of oral ketamine in pain management? Overall, ketamine was effective in 44% of patients, partially effective in 20%, opioid-sparing without pain reduction in 14%, and ineffective in ...

5. cda-amc.ca cda-amc.ca/sites/default/files/pdf/htis/2020/RC1281%20-%20Ketamine%20for%20CNCP%20Final.pdf

Ketamine for Chronic Non- Cancer Pain: A Review of ... Another systematic review found that topical ketamine and oral ketamine were not efficacious for treatment of neuropathic pain, while IV ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2018/016812s040lbl.pdf

ketamine - accessdata.fda.gov Ketamine has a wide margin of safety; several instances of unintentional administration of overdoses of. KETALAR (up to ten times that usually required) have ...

7. cdn.pfizer.com cdn.pfizer.com/pfizercom/products/material_safety_data/526.pdf

Material Safety Data Sheet Statement of Hazard: Harmful if swallowed. May be harmful if absorbed through the skin. Anesthetic drug: may cause central nervous system and cardiovascular ...

8. mayoclinic.org mayoclinic.org/drugs-supplements/ketamine-injection-route/description/drg-20075559

Ketamine (injection route) - Side effects & uses Ketamine may cause serious reactions (eg, brain or nerve problems) to children younger than 3 years of age.