"A Phase I Study of the Intrathecal Administration of Resiniferatoxin for Treating Severe Refractory Pain Associated with Advanced Cancer"

Summary: The NIDCR and the NIH Clinical Center have begun a clinical trial to evaluate a new treatment for intractable cancer pain. This novel, very potent treatment does not use opioid drugs like morphine. This is a phase I trial, meaning that it is the first time this will be tried in humans. It is a one-time intervention that should produce permanent pain relief. This study is currently recruiting participants.

Details: This is a phase I clinical trial to test the safety of an Investigational New Drug (IND). Previous studies in several animal pain models have demonstrated profound pain relief after the spinal administration of resiniferatoxin (RTX). RTX is a small organic compound extracted from a North African succulent plant and is similar to capsaicin, the active ingredient in hot pepper, although much more potent. The vanilloid receptor-1 (TRPV1) is a heat- and chemo-sensitive calcium/sodium ion channel selectively expressed in a subpopulation of pain-sensing primary afferent neurons. Binding of RTX or capsaicin to TRPV1 produces excessive ion channel open time, elevating intracellular calcium to cytotoxic levels and thereby deleting the target neurons. We propose to produce a selective and irreversible deletion of the neurons that transmit chronic pain sensations by injecting RTX into the cerebrospinal fluid surrounding the spinal cord and dorsal root ganglia (intrathecal injection). Our preclinical data in mouse, rat, dog and non-human primates demonstrate that deletion of these pain-specific neurons substantially attenuates pain and reduces the need for pain medications. At the same time, proprioception, locomotion and several types of thermal and mechanical pain sensations are completely preserved. Assessments of pain status will be made pre- and post-injection. Endpoints to be measured include: pain scores, amount of analgesic medication requested, quality of life, activity, and mood scores. The injection may cause transient pain and patients will be given a brief general anesthetic prior to the intrathecal injection of RTX. An escalating dosing regimen is planned with a total of 18-24 patients recruited. This therapy has significant and substantial implications for reducing the suffering and improving the quality of life in patients with advanced disease who are experiencing severe, refractory pain. Read more about this clinical trial at ClinicalTrials.gov.