Sativex for Treatment of Chemotherapy Induced Neuropathic Pain

Neuropathic Pain Clinical Trial

Official title: A Double Blind Placebo Controlled Crossover Pilot Trial of Sativex With Open Label Extension for Treatment of Chemotherapy Induced Neuropathic Pain

Status Completed

Clinical Trial Summary

Chemotherapy is often used to treat cancer and in many cases can cure it or extend life. Unfortunately many of the chemotherapeutic agents used in treating cancer can cause nerve damage, resulting in severe pain involving the extremities. This "neuropathic" pain causes significant suffering in cancer survivors and may also limit the amount of chemotherapy patients are able to tolerate in attempting to treat the cancer. There is evidence that cannabinoids can suppress chemotherapy evoked neuropathy in animal models, in some cases better than morphine. This study proposes to examine the effect of a cannabinoid extract (Sativex) in treatment of neuropathic pain caused by chemotherapy.

Clinical Trial Description

The problem of neuropathic pain:

A recent review has identified a neuropathic pain prevalence rate of 2-3% in the general population 1. Based on a Canadian population of 30 million, this means that close to one million Canadians suffer with neuropathic pain. Neuropathic pain is one of the most difficult types of persistent pain to treat effectively. No more than 50% 2 of patients with neuropathic pain obtain adequate relief using current treatments. This is related to the fact that there are numerous pathophysiological mechanisms that contribute to neuropathic pain. Neuropathic pain is now understood to involve neural responses in which both peripheral and central mechanisms contribute to the generation of spontaneous pain and evoked aspects including allodynia and hyperalgesia 3-5, Traditional approaches to neuropathic pain have involved the use of oral medications as single agents or in combination (NSAIDs, opioids, anticonvulsants, tricyclic type antidepressants) 6,7. Unfortunately this approach is often inadequate and accompanied by side effects. New treatments are needed for management of neuropathic pain

Neuropathic pain associated with chemotherapy:

Neuropathic pain associated with chemotherapy used for treatment of solid tumors (eg. paclitaxil, vincristine and cis-platin) is particularly resistant to treatment and is a growing clinical problem as chemotherapeutic regimes grow more successful in extending life. This type of neuropathic pain is particularly resistant to treatment and contributes to the overall level of suffering experienced by patients who recovering from cancer treatment with chemotherapy. There is pre-clinical evidence supporting that cannabinoid agonists may be helpful for treatment neuropathic pain caused by chemotherapy.

Cannabinoids in treatment of pain:

The potent anti-nociceptive and antihyperalgesic effects of cannabinoid agonists in animal models of acute and chronic pain, the presence of cannabinoid receptors in pain-processing areas of the brain, spinal cord and periphery and evidence supporting endogenous modulation of pain systems by cannabinoids, provide support that cannabinoids exhibit significant potential as analgesics8-13.

In addition sixteen of 19 randomized controlled trials examining cannabinoids in the treatment of pain have demonstrated a significant analgesic effect , nine of the positive trials involved neuropathic pain 14. Several of these trials examined a cannabinoid extract preparation Sativex15-20 proposed in the current trial.

What is the current standard of care for neuropathic pain caused by chemotherapy?

The current standard of care for neuropathic pain associated with chemotherapy is similar to that for management of chronic neuropathic pain. The approach consists of an interdisciplinary active participatory approach to living with incurable pain. This includes trials of pharmacotherapy (eg. anti-convulsant analgesics, tricyclic antidepressant analgesics and opioids), therapeutic exercise programs and training in coping strategies such as pacing and positive self talk. Such an approach is offered at multidisciplinary pain centres such as the Pain Management Unit (PMU) here at CDHA.

Study question:

Given the limitations of current best practice, the compelling pre-clinical work supporting that cannabinoids exhibit anti-nociceptive effects in neuropathic pain and more specifically in chemotherapy induced neuropathic pain and initial clinical trials supporting that Sativex exhibits efficacy in other types of neuropathic pain we propose a pilot trial of 30 patient to evaluate the effectiveness of Sativex in treatment of neuropathic pain caused by chemotherapy. If there are positive therapeutic effects in the pilot trial, we plan a subsequent randomized controlled trial. ;

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neuralgia
• Neuropathic Pain

• NCT number: NCT00872144
• Study type: Interventional
• Source: Nova Scotia Health Authority
• Status: Completed
• Phase: Phase 3
• Start date: June 2010
• Completion date: March 2013