(2R,6R)-Hydroxynorketamine a Novel Therapeutic Analgesic for the Treatment of Neuropathic Pain
Abstract
Objectives and Rationale: Neuropathic pain is pain that arises from the nerves and is described as numbness, tingling, loss of feeling, and stabbing by the patient. Neuropathic pain can occur due to an injury, diabetes, alcoholism, or unknown causes. This pain is often relentless, affecting the individual s ability to work, perform daily activities of life, and limits the patient s ability to sleep. The yearly cost of neuropathic pain in the United States is more than $100 billion. Neuropathic pain is very difficult to treat and patients frequently do not respond to the medications that are the mainstay of the treatment. Common drugs treatments include antidepressants, gabapentin, and pregabalin are often not well tolerated by patients, and physicians frequently need to prescribe opioid analgesics to treat the pain. Ketamine is a drug that has shown some promise in the treatment of neuropathic pain when administered as a series of infusions over days or weeks. The pain relief from ketamine lasts much longer than the time that drug can be detected in the body and can provide pain relief for weeks to months in patients that have failed other treatments. Unfortunately, ketamine has undesirable side effects including nausea, vomiting, hallucinations, delusional thoughts, and can cause a state of unease or general dissatisfaction with life. Ketamine also has the potential to lead to drug abuse. When administered ketamine is rapidly metabolized into over 20 metabolites including (2R,6R)-Hydroxynorketamine (HNK). HNK appears to have antidepressant activity and is currently being studied under a U.S. Food and Drug Administration safety and tolerability protocol in humans. The investigators of this proposal have demonstrated that HNK has analgesic properties in animal models of pain. Unlike ketamine, HNK has not been found to have the same dose limiting side effects as ketamine, it does not act at opioid receptors, and does not appear to have the potential to lead to drug abuse. The dose of HNK that is currently being studied in humans appears to overlap with the analgesic dosage range that has been shown in animal studies. However, the analgesic activity of HNK in humans is unknown and needs to be evaluated to move forward for approval of (2R,6R)-HNK as an analgesic for clinical use. The proposed study specifically addresses the Fiscal Year 2022 Chronic Pain Management Research Program Clinical Exploration Award Focus Area effectiveness of a novel, nonopioid or untested approach to chronic pain management. The objective of this study will be to provide evidence that an infusion of HNK will provide analgesic benefit to subjects with chronic NP. It will also access the duration of the analgesic effect and safety of the use of a single dose of (2R,6R)-HNK in the treatment of chronic NP. The study will include patients (n=25) with chronic neuropathic pain of the extremities. Patients will receive three different drug infusions in this study separated by 35 days. They will receive an infusion of (2R,6R)-HNK, ketamine, or saline decided by chance (coin flip). All subjects will receive each of the study drugs. The investigators administering the drug and evaluating the patient will not know which drug the patient received. The study will evaluate the subjects reported pain intensity and unpleasantness and well as the qualities of their pain (burning, aching, tingling, stabbing) 1 week before 28 days after each treatment. They will also measure physical activity, sleep quality and quantity, and the amount that pain interferes with their daily activities and quality of life. We will also assess safety and side effects of the treatment. If we are successful in showing the analgesia and safety benefit of HNK in our study it will lead to additional studies of the use of HNK in other acute and chronic pain conditions. This study will also support the decision of the U.S. Food and Drug Administration on making H
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310834
Entities
People
- Asokumar Buvanendran
Organizations
- Rush University Medical Center
- United States Army