Ketamine + Cognitive Behavioral Therapy for Neuropathic Pain
(PSYKED-NP Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
Sponsor: Akash Goel
Must not be taking: Theophylline, Aminophylline, others
Disqualifiers: Schizophrenia, Bipolar, Hypertension, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?The purpose of the study is to investigate new therapies to alleviate pain on neuropathic chronic pain. At this time, the main purpose is to complete a feasibility or pilot study with 60 participants suffering from neuropathic chronic pain. Participants will be randomized to (1) Ketamine (Hydrochloride) HCL; (2) psychotherapy (using Cognitive Behavioral Therapy); or (3) a combination of Ketamine HL and psychotherapy.
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 data supports the effectiveness of the drug ketamine for neuropathic pain?
Research shows that ketamine, a drug with strong pain-relieving properties, can reduce pain intensity and improve quality of life for some patients with neuropathic pain. However, its effectiveness varies, and it may cause side effects in many patients.
12345Is the combination of ketamine and cognitive behavioral therapy safe for treating neuropathic pain?
Ketamine has been used safely in low doses for chronic pain and depression, with improved safety profiles at these doses compared to its use as an anesthetic. However, some side effects like psychiatric and cardiovascular issues have been reported, especially with repeated doses. Cognitive behavioral therapy is generally considered safe for treating various conditions, including neuropathic pain.
16789How does the treatment of Ketamine + Cognitive Behavioral Therapy for neuropathic pain differ from other treatments?
This treatment is unique because it combines ketamine, a drug known for its strong pain-relieving properties, with cognitive behavioral therapy (CBT), a psychological approach that helps patients manage pain by changing their thought patterns. Ketamine works by blocking certain receptors in the brain to reduce pain, while CBT provides tools to cope with pain mentally, offering a dual approach that targets both physical and emotional aspects of neuropathic pain.
59101112Eligibility Criteria
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.
+1 more
Trial Timeline
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
Participant Groups
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.
3Treatment groups
Experimental Treatment
Active Control
Group I: Ketamine + PsychotherapyExperimental Treatment1 Intervention
Group II: Psychotherapy onlyActive Control1 Intervention
Group III: Ketamine onlyActive Control1 Intervention
Cognitive Behavioral Therapy is already approved in European Union, United States, Canada, Australia 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)
🇦🇺 Approved in Australia as Cognitive Behavioral Therapy for:
- Anxiety disorders
- Depressive disorders
- Eating disorders
- Post-traumatic stress disorder (PTSD)
- Obsessive-compulsive disorder (OCD)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
St. Michael's HospitalToronto, Canada
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Who Is Running the Clinical Trial?
Akash GoelLead Sponsor
Unity Health TorontoLead Sponsor
References
Evidence Mapping Based on Systematic Reviews of Cognitive Behavioral Therapy for Neuropathic Pain. [2023]This evidence mapping is aimed at identifying, summarizing, and analyzing the available evidence on cognitive behavioral therapy (CBT) for neuropathic pain (NP).
N of 1 randomised controlled trials of oral ketamine in patients with chronic pain. [2019]Anecdotal reports suggest that the general anaesthetic drug ketamine, taken orally in low doses, can give rise to some extra analgesia in patients with refractory neuropathic pain. This study was designed to determine the proportion of patients with chronic neuropathic pain responding to oral ketamine, and then to separate the true treatment effect from non-specific effects by means of an n of 1 randomised controlled trial. Twenty-one patients gave informed consent and completed daily pain diaries and continued on their usual treatments (drug and non-drug) for the duration of the study. After a 'baseline' week, oral ketamine was taken once a day for 1 week. The dose of 20 mg was increased each day until an analgesic effect was noticed or adverse effects occurred, or until a maximum of 100 mg was reached. Those patients responding to oral ketamine were then entered into the n of 1 randomised trial which consisted of three treatment/placebo week pairs. Twelve patients did not progress to the n of 1 trial because of no benefit and/or intolerable adverse effects (dizziness, drowsiness etc.). Nine patients completed the n of 1 trial; there was no difference between the ketamine and placebo weeks in six patients; one patient demonstrated effective analgesia with ketamine, but it was of short duration and marred by unpleasant adverse effects; two patients showed some evidence of a beneficial response to ketamine, and continued with the oral ketamine after the trial. We conclude that oral ketamine only gave rise to an extra analgesic response in three out of 21 patients with chronic neuropathic pain (14%). Adverse effects limited the use of the drug in almost half of the patients. The n of 1 trial was useful in demonstrating no true therapeutic effect for the ketamine in two thirds of the patients progressing to that part of the trial.
Ketamine in chronic pain management: an evidence-based review. [2022]Ketamine has diverse effects that may be of relevance to chronic pain including: N-methyl-D-aspartic acid, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, kainate, gamma-aminobutyric acid(A) receptors; inhibition of voltage gated Na(+) and K(+) channels and serotonin, dopamine re-uptake. Ketamine has been in clinical practice for over 30 yr; however, there has been little formal research on the effectiveness of ketamine for chronic pain management. In this review we evaluate the available clinical data as a basis for defining the potential use of ketamine for chronic pain. Literature referenced in this review was obtained from a computer search of EMBASE and MEDLINE from 1966 through August, 2002. Search terms included ketamine, ketalar, pain, painful, analgesic, and analgesia. Abstracts were screened for relevance and publications relating to chronic pain use were obtained. Levels of evidence were stratified according to accepted guidelines (level I-IV). For central pain, there is level II and level IV evidence of efficacy for parenteral and oral ketamine. For complex regional pain syndromes, there is only level IV evidence of efficacy of epidural ketamine. For fibromyalgia, there is level II evidence of pain relief, reduced tenderness at trigger points, and increased endurance. For ischemic pain, a level II study reported a potent dose-dependent analgesic effect, but with a narrow therapeutic window. For nonspecific neuropathic pain, level II and level IV studies reported divergent results with questionable long-term effects on pain. For phantom limb pain and postherpetic neuralgia, level II and level II studies provided objective evidence of reduced hyperpathia and pain relief was usually substantial either after parenteral or oral ketamine. Acute on chronic episodes of severe neuropathic pain represented the most frequent use of ketamine as a "third line analgesic," often by IV or subcutaneous infusion (level IV). In conclusion, the evidence for efficacy of ketamine for treatment of chronic pain is moderate to weak. However, in situations where standard analgesic options have failed ketamine is a reasonable "third line" option. Further controlled studies are needed.
Analgesic effect of oral ketamine in chronic neuropathic pain of spinal origin: a case report. [2019]Ketamine is an injectable anesthetic induction agent that has been reported to have analgesic activity in pain from a variety of mechanisms, but predominantly in neuralgic and dysesthetic neuropathic pain. In this case report we illustrate the effectiveness of ketamine in a patient with neuropathic pain resulting from cauda equina trauma. Among the issues addressed are the role of pretreatment with haloperidol to prevent ketamine-induced psychomimetic effects, the potential for fewer side effects and a need for lower doses when ketamine is administered orally, and the need for further study regarding appropriate monitoring parameters during the titration phase. Oral ketamine can be effective in treatment refractory chronic neuropathic pain of spinal origin.
Efficacy and Safety of Ketamine in the Treatment of Neuropathic Pain: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. [2022]Ketamine is a N-methyl-D-aspartate (NMDA) antagonist with strong analgesic properties. Its addition to the treatment of neuropathic pain may reduce pain intensity and improve overall quality of life. A systematic review and meta-analysis of randomized controlled trials was performed to investigate the addition of ketamine to the treatment of patients with neuropathic pain.
Side-effects associated with ketamine use in depression: a systematic review. [2019]This is the first systematic review of the safety of ketamine in the treatment of depression after single and repeated doses. We searched MEDLINE, PubMed, PsycINFO, and Cochrane Databases and identified 288 articles, 60 of which met the inclusion criteria. After acute dosing, psychiatric, psychotomimetic, cardiovascular, neurological, and other side-effects were more frequently reported after ketamine treatment than after placebo in patients with depresssion. Our findings suggest a selective reporting bias with limited assessment of long-term use and safety and after repeated dosing, despite these being reported in other patient groups exposed to ketamine (eg, those with chronic pain) and in recreational users. We recommend large-scale clinical trials that include multiple doses of ketamine and long-term follow up to assess the safety of long-term regular use.
Safety of Intranasal Ketamine for Reducing Uncontrolled Cancer-Related Pain: Protocol of a Phase I/II Clinical Trial. [2020]Approximately 12 million Americans are affected with cancer. Of these, 53% experience pain at all stages of cancer. Pain may remain uncontrolled despite high-dose opioid therapy, and opioids have many well-documented harmful side effects. Intranasal ketamine has been shown to be effective in controlling breakthrough noncancer pain in a double-blind randomized control trial (DBRCT) by Carr et al in 2003 as well as to help with depression in a DBRCT by Lapidus et al in 2014. We seek to obtain preliminary data on the safety, feasibility, and utility of this novel technique for the treatment of uncontrolled cancer pain.
Ketamine Use for Cancer and Chronic Pain Management. [2021]Ketamine, an N-methyl-D-aspartate receptor antagonist, is widely known as a dissociative anesthetic and phencyclidine derivative. Due to an undesirable adverse event profile when used as an anesthetic it had widely fallen out of human use in favor of more modern agents. However, it has recently been explored for several other indications such as treatment resistant depression and chronic pain. Several recent studies and case reports compiled here show that ketamine is an effective analgesic in chronic pain conditions including cancer-related neuropathic pain. Of special interest is ketamine's opioid sparing ability by counteracting the central nervous system sensitization seen in opioid induced hyperalgesia. Furthermore, at the sub-anesthetic concentrations used for analgesia ketamine's safety and adverse event profiles are much improved. In this article, we review both the basic science and clinical evidence regarding ketamine's utility in chronic pain conditions as well as potential adverse events.
Long-term intrathecal S(+)-ketamine in a patient with cancer-related neuropathic pain. [2018]Neuropathic pain sometimes needs invasive pain therapy. We present the case of a patient with cancer-related neuropathic pain untreatable with conventional pain therapy after tumour-embolization. The patient was treated successfully with intrathecal (i.t.) administration of S(+)-ketamine, in addition to morphine. Plasma concentrations of S(+)-ketamine were measured regularly throughout the treatment. Continuous i.t. administration of S(+)-ketamine over a period of 3 months demonstrated low plasma levels and no unwanted side-effects.
Ketamine and Magnesium for Refractory Neuropathic Pain: A Randomized, Double-blind, Crossover Trial. [2020]Ketamine is often used for the management of refractory chronic pain. There is, however, a paucity of trials exploring its analgesic effect several weeks after intravenous administration or in association with magnesium. The authors hypothesized that ketamine in neuropathic pain may provide pain relief and cognitive-emotional benefit versus placebo and that a combination with magnesium may have an additive effect for 5 weeks.
Case Report of Subanesthetic Intravenous Ketamine Infusion for the Treatment of Neuropathic Pain and Depression with Suicidal Features in a Pediatric Patient. [2020]Chronic neuropathic pain and depression are often comorbid. Ketamine has been used to treat refractory pain. There is emerging evidence for use in depression. We present a case of a pediatric patient who was successfully treated with subanesthetic intravenous ketamine infusion for chronic neuropathic pain and suicidality.
Chronic administration of ketamine for analgesia. [2013]Use of the dissociative anesthetic ketamine in subanesthetic doses has demonstrated efficacy in neuropathic pain. This article reviews the scientific and clinical literature on ketamine. Mechanisms of both central and peripheral neuropathic pain are described. Studies of ketamine analgesia in postherpetic neuralgia, phantom pain, complex regional pain syndrome and cancer pain are reviewed. A range of administration methods for ketamine including neuroaxial administration are described.