Gabapentin + Ketamine for Head and Neck Cancer Pain Management
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Dianne Lou
Must not be taking: Gabapentin, Ketamine
Disqualifiers: Seizure disorder, Schizophrenia, others
No Placebo Group
Trial Summary
What is the purpose of this trial?This is a study to establish a safe and feasible dose for prophylactic use of a combination of gabapentin and ketamine in head and neck cancer patients undergoing chemoradiation.
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 taking gabapentin or ketamine.
What data supports the effectiveness of the drug combination of Gabapentin and Ketamine for managing head and neck cancer pain?
Gabapentin has been shown to reduce opioid use in head and neck cancer patients, indicating its potential effectiveness in managing pain. Additionally, ketamine has been used to treat pain in various settings, including chronic pain and postoperative pain, suggesting it may also contribute to pain relief in cancer patients.
12345Is gabapentin generally safe for humans?
Gabapentin is generally considered safe when used as prescribed, with common side effects like dizziness and drowsiness. However, it can cause serious issues if misused or in people with kidney problems, and there is potential for abuse.
678910How does the drug combination of Gabapentin and Ketamine differ from other treatments for head and neck cancer pain management?
The combination of Gabapentin and Ketamine for head and neck cancer pain management is unique because it targets pain through different mechanisms than traditional opioids, with Ketamine acting as an NMDA receptor antagonist to reduce pain and potentially lower opioid use. This approach may offer pain relief without the typical side effects associated with opioids, addressing an unmet need in managing severe pain from cancer treatments.
24111213Eligibility Criteria
This trial is for adults over 21 with advanced but non-metastatic head and neck cancer, who are about to undergo or are currently receiving radiation or chemoradiation. Participants must be able to consent and speak English. Those already on gabapentin or ketamine, with a history of seizures, schizophrenia, high brain pressure, or poor kidney function cannot join.Inclusion Criteria
I am 21 years old or older.
My cancer is in the head or neck area, confirmed by a biopsy.
My cancer is advanced but hasn't spread to distant parts of my body.
+4 more
Exclusion Criteria
I am currently taking gabapentin or ketamine.
I have had issues with high pressure inside my skull.
You have been diagnosed with schizophrenia in the past.
+4 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive gabapentin and ketamine three times per day during chemoradiation
28 days
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Extension
Participants are assessed for pain, symptom burden, functionality, and quality of life
Up to 30 days post-treatment
Participant Groups
The study is testing the safety and appropriate dose of gabapentin combined with ketamine given before treatment to prevent acute and chronic pain in patients undergoing chemoradiation for head and neck cancer.
1Treatment groups
Experimental Treatment
Group I: Gabapentin plus KetamineExperimental Treatment2 Interventions
Gabapentin and Ketamine will be taken 3 times per day.
Gabapentin is already approved in United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as Neurontin for:
- Postherpetic neuralgia
- Partial-onset seizures
🇪🇺 Approved in European Union as Gabapentin for:
- Peripheral neuropathic pain
- Partial-onset seizures
🇨🇦 Approved in Canada as Gabapentin for:
- Postherpetic neuralgia
- Partial-onset seizures
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Vanderbilt-Ingram Cancer CenterNashville, TN
Loading ...
Who Is Running the Clinical Trial?
Dianne LouLead Sponsor
Natalie LockneyLead Sponsor
References
Topical and peripheral ketamine as an analgesic. [2021]Ketamine, in subanesthetic doses, produces systemic analgesia in chronic pain settings, an action largely attributed to block of N-methyl-D-aspartate receptors in the spinal cord and inhibition of central sensitization processes. N-methyl-D-aspartate receptors also are located peripherally on sensory afferent nerve endings, and this provided the initial impetus for exploring peripheral applications of ketamine. Ketamine also produces several other pharmacological actions (block of ion channels and receptors, modulation of transporters, anti-inflammatory effects), and while these may require higher concentrations, after topical (e.g., as gels, creams) and peripheral application (e.g., localized injections), local tissue concentrations are higher than those after systemic administration and can engage lower affinity mechanisms. Peripheral administration of ketamine by localized injection produced some alterations in sensory thresholds in experimental trials in volunteers and in complex regional pain syndrome subjects in experimental settings, but many variables were unaltered. There are several case reports of analgesia after topical application of ketamine given alone in neuropathic pain, but controlled trials have not confirmed such effects. A combination of topical ketamine with several other agents produced pain relief in case, and case series, reports with response rates of 40% to 75% in retrospective analyses. In controlled trials of neuropathic pain with topical ketamine combinations, there were improvements in some outcomes, but optimal dosing and drug combinations were not clear. Given orally (as a gargle, throat swab, localized peritonsillar injections), ketamine produced significant oral/throat analgesia in controlled trials in postoperative settings. Topical analgesics are likely more effective in particular conditions (patient factors, disease factors), and future trials of topical ketamine should include a consideration of factors that could predispose to favorable outcomes.
Use of Various Doses of S-Ketamine in Treatment of Depression and Pain in Cervical Carcinoma Patients with Mild/Moderate Depression After Laparoscopic Total Hysterectomy. [2021]BACKGROUND This study investigated the effects of various doses of S-ketamine on depression and pain management of cervical carcinoma patients with mild/moderate depression. MATERIAL AND METHODS This randomized, double-blind, controlled study included 417 cervical carcinoma patients who received laparoscopic modified radical hysterectomy from April 2015 to July 2018 and who also had mild/moderate depression symptoms based on HAMD-17 scores (8~24). All patients were randomized into 4 groups: 1) the control group, 2) the racemic ketamine group, 3) the high-dose S-ketamine group; and 4) the low-dose S-ketamine group. Pain was assessed using the Visual Analogue Score (VAS), and depression was assessed using theHAMD-17 score. Serum levels of BDNF and 5-HT were measured. RESULTS The 4 groups of patients showed no significant differences in operation time, bleeding volume, hospitalization duration, or complications. The high-dose S-ketamine group showed significantly lower VAS and HAMD-17 scores than all other groups at 1 day and 3 days postoperatively, but no differences were observed in the low-dose S-ketamine group and the racemic ketamine group. The high-dose S-ketamine group showed significantly higher serum BDNF and 5-HT levels at 1 day and 3 days after surgery. However, 1 week after surgery, no difference was observed in any of the treatment groups. CONCLUSIONS At subanesthetic dose, both 0.5 mg/kg and 0.25 mg/kg S-ketamine improved short-term depression and pain for cervical carcinoma patients after surgery, and the effects were better than with the same dose of racemic ketamine.
Implementing practice change in chronic cancer pain management: clinician response to a phase III study of ketamine. [2015]An adequately powered, double-blind, multisite, randomised controlled trial has shown no net clinical benefit for subcutaneous ketamine over placebo in the management of cancer pain refractory to combination opioid and co-analgesic therapy. The results of the trial were disseminated widely both nationally and internationally.
Development of a sublingual/oral formulation of ketamine for use in neuropathic pain: Preliminary findings from a three-way randomized, crossover study. [2021]Enterally administered low-dose ketamine is being used increasingly to treat pain states. However, suitable oral or sublingual formulations are not available. The objective of the study was to develop a lozenge formulation of ketamine for use in patients with neuropathic pain, and to investigate its storage stability and bioavailability after oral or sublingual administration.
Effectiveness of gabapentin in reducing opioid requirements after radiation in head and neck cancer in a single institution. [2022]Gabapentin has been shown to reduce opioid use in head and neck cancer patients. Here, we examine the efficacy of prophylactic gabapentin at reducing opioid use in these patients at our institution.
Gabapentin-induced neurologic toxicities. [2018]Gabapentin is an antiepileptic drug approved for the treatment of postherpetic neuralgia and as adjunctive therapy for partial seizures. The drug has been shown to be safe and nontoxic. The current literature has limited reports of neurologic toxicity associated with gabapentin therapy in patients with or without renal dysfunction. We describe the case of a 75-year-old man with renal dysfunction who developed neurologic toxicity due to gabapentin accumulation. Future studies are warranted to confirm the neurologic adverse effects of gabapentin, including any additional risks in patients with renal dysfunction.
An acute gabapentin fatality: a case report with postmortem concentrations. [2022]Gabapentin (GBP) (Neurontin®, Horizant®, Gralise®) is a widely prescribed medication used primarily for the treatment of epilepsy and neuropathic pain. GBP has a favorable adverse effect profile in therapeutic dosing with the most common reported effects being dizziness, fatigue, drowsiness, weight gain, and peripheral edema. Even with intentional GBP self-poisonings, serious effects are rare. A 47-year-old female was found dead at work with her daughter's bottle of GBP 600 mg. There were 26 tablets missing and the decedent's only known medication was hydrocodone/acetaminophen. Following initial detection by an alkaline drug screen (GC-MS), analysis utilizing specific liquid chromatography-mass spectrometry revealed an elevated postmortem GBP peripheral blood concentration of 37 mg/L, central blood 32 mg/L, liver 26 mg/kg, vitreous 32 mg/L, and gastric contents 6 mg. Screening for volatiles, drugs of abuse, alkaline compounds, and acid/neutral compounds was negative with the exception of ibuprofen (
A qualitative analysis of gabapentin misuse and diversion among people who use drugs in Appalachian Kentucky. [2021]Gabapentin, an anticonvulsant and analgesic for postherpetic neuralgia, has been thought to have no abuse potential despite numerous published reports to the contrary. Gabapentin has been linked with impaired driving and opioid use, highlighting the need to more fully understand its risk profile. Thirty-three individuals reporting recent nonmedical use of gabapentin were recruited from two ongoing longitudinal studies of drug users in Appalachian Kentucky to participate in focus groups. Four sessions were held (two in the community and two in jail settings), during which participants responded to questions regarding their personal experiences with gabapentin misuse. Focus group participants were similar to other gabapentin users in the larger cohort studies with respect to demographics and drug use behaviors. Overall, the sample reported having initiated gabapentin more than 10 years earlier after having it prescribed for a legitimate, though generally off-label, medical indication (e.g., pain, anxiety, opioid detoxification). Participants reported use of gabapentin in combination with buprenorphine, other opioids, cocaine, and caffeine to produce sought-after central nervous system effects (e.g., muscle relaxation, pain reduction, sleep induction, feeling drunk, and feeling "high"). Focus group responses highlighted the low cost of gabapentin for the purpose of getting high and noted increasing popularity in the community, particularly over the last 2 years. Gabapentin was a prominent drug of abuse in two cohorts of the primarily opioid-using individuals. Providers should be aware of gabapentin's abuse potential, and a reexamination of the need for scheduling is warranted. (PsycINFO Database Record
Gabapentin-Induced Myokymia: A Case Report. [2021]Gabapentin is a commonly used medication for neuropathic pain and epilepsy that is prescribed by a wide range of medical specialties. Adverse effects including asterixis and myoclonus have been described in patients with chronic kidney disease, but myokymia has not been previously reported.
A randomized controlled study of 6% gabapentin topical formulation for chronic kidney disease-associated pruritus. [2021]Novel agents with good safety profiles are needed in the management of chronic kidney disease-associated pruritus (CKD-AP). This study aims to assess the efficacy and safety of topical gabapentin in the treatment of CKD-AP.
Efficacy of ketamine mouthwash in the management of oral and pharyngeal toxicity associated with head and neck chemoradiotherapy: protocol for a phase II, Simon's two-stage trial. [2023]Curative intent treatment of head and neck cancer (HNC) is frequently radiation therapy over 7 weeks with concurrent chemotherapy. This regimen is effective but carries a burden of toxicity leading to severe pain and treatment breaks portending inferior outcomes. Conventional palliation methods include opioids, anticonvulsants and local anaesthetics. Breakthrough toxicities are nevertheless ubiquitous and present an urgent unmet need. Ketamine is an inexpensive drug with mechanisms of analgesia outside the opioid pathway including N-methyl-D-aspartate (NMDA) receptor antagonism and a pharmacologically unique property of opioid desensitisation. Systemic ketamine is validated in randomised controlled trials for efficacy in reducing pain and/or opioid burden in the oncologic setting. Literature supports peripherally administered ketamine for pain control without systemic toxicity. These data support our rationale of using ketamine mouthwash to decrease acute toxicity of curative treatment of HNC, the efficacy of which is our aim to elucidate.
Pharmacological Management of Neuropathic Pain after Radiotherapy in Head and Neck Cancer Patients: A Systematic Review. [2023]Background: Neuropathic pain (NP) in head and neck cancer (HNC) patients represents a treatment challenge. Most studies investigating drugs against NP are conducted in patients suffering with diabetic neuropathy or postherpetic neuralgia, while data are limited in cancer pain management. Additionally, regarding cancer therapy-related NP, most of the studies do not focus on HNC patients. The aim of this review is to identify the studies on systematically administered medication for NP management that included HNC patients under radiotherapy. Methods: A systematic literature search was performed, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, in PubMed, Cochrane Library, Web of Science and ClinicalTrials.gov on 30 October 2021. The medical subject heading (MeSH) terms were (“head and neck cancer” OR “tumor”) AND “neuropathic pain” AND “medication” AND “radiotherapy.” The Cochrane Collaboration tool was used for quality assessment. Results: The search identified 432 articles. Three more articles were identified after searching the reference lists of the retrieved articles. A total of 10 articles met the eligibility inclusion criteria and were included in this review; 6 on gabapentin, 1 on pregabalin, 1 on nortriptyline, 1 on methadone, and 1 on ketamine. Statistically significant results in pain reduction compared to placebo or standard pain medication were found in the studies on pregabalin (p = 0.003), methadone (p = 0.03), ketamine (p = 0.012), and in two out of six gabapentin studies (p
Oral ketamine in the palliative care setting: a review of the literature and case report of a patient with neurofibromatosis type 1 and glomus tumor-associated complex regional pain syndrome. [2021]Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has been shown to be effective not only for its anesthetic properties but also for the analgesic and opiate-sparing effects. However, data on efficacy and safety of oral ketamine for the treatment of neuropathic or cancer pain syndromes is limited with most of the evidence based on small clinical trials and anecdotal experiences. In this review, we will analyze the clinical data on oral ketamine in the palliative care setting. After an extensive search using five major databases, a total of 19 relevant articles were included. No official clinical guidelines for the use of oral ketamine in this patient population were found. Studies on oral ketamine for cancer and neuropathic pain have shown mixed results which could be partially due to significant differences in hepatic metabolism. In addition, we will include a case report of a 38-year-old female with neurofibromatosis type 1 (NF1) with history of chronic, severe pain in her fingertips secondary to multiple glomus tumors which evolved into CRPS resistant to multiple therapies but responsive to oral ketamine. Based on our experience with oral ketamine, this drug should be administered after an intravenous trial to monitor response and side effects in patients with an adequate functional status. However, patients in the palliative care and hospice setting, especially the one at the end of their lives, may also benefit from oral ketamine even if an intravenous trial is not feasible.