Neuropathic PainPhase 3NCT00872144
Sativex for Treatment of Chemotherapy Induced Neuropathic Pain
A Phase 3 study testing Sativex in people with Neuropathic Pain, run by Mary Lynch at 1 site in Canada.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neuropathic Pain
- What is being tested?
- Sativex
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteCanada
- Study dates
- Jun 2010to Mar 2013
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age >18 years
- Neuropathic pain beginning after chemotherapy with paclitaxil, vincristine or cis-platin that has been present for 3 months or longer.
- Presence of allodynia, hyperalgesia or hypoesthesia on sensory testing in the area of pain.
- Moderate to severe pain, as defined by an average 7-day pain score of greater than 4.0 on an 11-point numerical rating scale for pain intensity (NRS-PI).
- Medications must have been stable for at least14 days.
- Ability to follow the protocol
- Willing and able to give written informed consent.
Who cannot join
- Ischemic heart disease
- Personal history of schizophrenia or psychotic disorder
- Family history of schizophrenia or psychotic disorder in first degree family member (parent, sibling or child)
- Allergy to cannabinoids
- Presence of any other clinically significant medical disorder (other than the cancer requiring chemotherapy) on history or physical exam that would compromise the participants' safety in the trial as judged by the study physician
Trial locations and contacts
1 site in 1 country.
Canada1 site
Queen Elizabeth II Health Sciences Centre, Pain Management Unit
Halifax, Nova Scotia, B3H 2Y9
About this study
Official title: A Double Blind Placebo Controlled Crossover Pilot Trial of Sativex With Open Label Extension for Treatment of Chemotherapy Induced Neuropathic Pain
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.
Read the detailed 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.
- Conditions
- Neuropathic Pain
- Being tested
- Sativex
- Medical subject headings
- Neuralgia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SativexDrug
Sativex (or placebo) will be dispensed identical 5.5 ml containers. Participants will be instructed to start with a dose of 1 spray trans-mucosally at 1800 hrs. If there are no limiting adverse effects such as sedation or dizziness, participants will be instructed to increase the dose to 2 sprays- one in the morning and the other in the early evening on day two. Participants may increase the dose by 1-2 sprays per day to a maximum dose of 12 sprays per day given 3 sprays 4 times per day. In the initial titration phase participants will be instructed to space each dose actuation 15 minutes apart until accustomed to the preparation. Participants will titrate the dose to a level where they obtain an analgesic effect without limiting side effects.
| Study group | Role | What they receive |
|---|---|---|
| Sativex | Active comparator | Not described Receives: Drug: Sativex |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in the NRS-PI from baseline to the final week of stable dose treatment)
Measured: Patients will titrate the dose to a level where they obtain an analgesic effect without limiting side effects (week 3)
Participants gaining a 30% or greater reduction in the NRS-PI
Measured: Patients will titrate the dose to a level where they obtain an analgesic effect without limiting side effects (week 3)
Secondary outcomes (1)
Secondary outcome measures will include measures in the remaining domains (suggested by IMMPACT). These include SF36, Quantitative sensory examination, Global Impression of Change, PGIC and Patient Satisfaction Scale, PSS
Measured: After stable dosing is achieved (week 3)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2009 (estimated)
- Study startJun 2010
- Primary completionDec 2012
- Study completionMar 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Neuropathic PainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mary Lynch
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Mary Lynch, Nova Scotia Health Authority
- Investigators
- Mary E Lynch, MD, Principal investigator, Nova Scotia Health Authority
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00872144
- Sponsor's protocol ID
- CDHA-RS/2009-316
- Status last verified
- Mar 2014
- First submitted
- 25 Mar 2009
- Last updated
- 7 Mar 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Lynch ME, Cesar-Rittenberg P, Hohmann AG. A double-blind, placebo-controlled, crossover pilot trial with extension using an oral mucosal cannabinoid extract for treatment of chemotherapy-induced neuropathic pain. J Pain Symptom Manage. 2014 Jan;47(1):166-73. doi: 10.1016/j.jpainsymman.2013.02.018. Epub 2013 Jun 4.
PubMed 23742737
Study at a glance
From the registry record, last updated by the sponsor on 7 Mar 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double Blind Placebo Controlled Crossover Pilot Trial of Sativex With Open Label Extension for Treatment of Chemotherapy Induced Neuropathic Pain
- ClinicalTrials.gov ID
- NCT00872144
- Acronym / sponsor ID
- CDHA-RS/2009-316
- Conditions
- Neuropathic Pain
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Mary LynchUniversity, hospital or other
- Study start
- Jun 2010
- Primary completion
- Dec 2012 (actual)
- Study completion
- Mar 2013 (actual)
- First posted
- 31 Mar 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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
- Primary purpose
- Treatment
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sativex | Active comparator | Drug: Sativex |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age >18 years
- Neuropathic pain beginning after chemotherapy with paclitaxil, vincristine or cis-platin that has been present for 3 months or longer.
- Presence of allodynia, hyperalgesia or hypoesthesia on sensory testing in the area of pain.
- Moderate to severe pain, as defined by an average 7-day pain score of greater than 4.0 on an 11-point numerical rating scale for pain intensity (NRS-PI).
- Medications must have been stable for at least14 days.
Key exclusion criteria (5 listed)
- Ischemic heart disease
- Personal history of schizophrenia or psychotic disorder
- Family history of schizophrenia or psychotic disorder in first degree family member (parent, sibling or child)
- Allergy to cannabinoids
- Presence of any other clinically significant medical disorder (other than the cancer requiring chemotherapy) on history or physical exam that would compromise the participants' safety in the trial as judged by the study physician
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SativexSativex (or placebo) will be dispensed identical 5.5 ml containers. Participants will be instructed to start with a dose of 1 spray trans-mucosally at 1800 hrs. If there are no limiting adverse effects such as sedation or dizziness, participants will be instructed to increase the dose to 2 sprays- one in the morning and the other in the early evening on day two. Participants may increase the dose by 1-2 sprays per day to a maximum dose of 12 sprays per day given 3 sprays 4 times per day. In the initial titration phase participants will be instructed to space each dose actuation 15 minutes apart until accustomed to the preparation. Participants will titrate the dose to a level where they obtain an analgesic effect without limiting side effects. | Drug | Sativex |
Primary outcome
Change in the NRS-PI from baseline to the final week of stable dose treatment)
Time frame: Patients will titrate the dose to a level where they obtain an analgesic effect without limiting side effects (week 3)
Participants gaining a 30% or greater reduction in the NRS-PI
Time frame: Patients will titrate the dose to a level where they obtain an analgesic effect without limiting side effects (week 3)
1 secondary outcome
Secondary outcome measures will include measures in the remaining domains (suggested by IMMPACT). These include SF36, Quantitative sensory examination, Global Impression of Change, PGIC and Patient Satisfaction Scale, PSS
Time frame: After stable dosing is achieved (week 3)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Mar 2014.
- Results publication: PubMed 23742737Lynch ME, Cesar-Rittenberg P, Hohmann AG. A double-blind, placebo-controlled, crossover pilot trial with extension using an oral mucosal cannabinoid extract for treatment of chemotherapy-induced neuropathic pain. J Pain Symptom Manage. 2014 Jan;47(1):166-73. doi: 10.1016/j.jpainsymman.2013.02.018. Epub 2013 Jun 4.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mary E Lynch, MD principal investigator
Nova Scotia Health Authority
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Sativex in people with Neuropathic Pain, run by Mary Lynch at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Mar 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in the NRS-PI from baseline to the final week of stable dose treatment) (time frame: Patients will titrate the dose to a level where they obtain an analgesic effect without limiting side effects (week 3)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00872144, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Mar 2014.