Neuropathic PainPhase 2NCT00488969
Effectiveness of Controlled-Release Morphine for Chronic Neuropathic Pain After Spinal Cord Injury
A Phase 2 study testing Modified-release morphine in people with Neuropathic Pain and Spinal Cord Injury, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.
Trial summary
We would like to learn if a medicine called "modified-release morphine sulfate" (Avinza) helps reduce Spinal Cord Injury (SCI)-related pain that has lasted a long time. "Modified-release" means that the medicine in the capsules is slowly released to the body, instead of being released all at once. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Neuropathic Pain, Spinal Cord Injury
- What is being tested?
- Modified-release morphine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2007to Jul 2013
- Phase
- Phase 2
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 - 65
- Diagnosis of traumatic spinal cord injury
- Neuropathic pain (pain related to the nervous system) rated at least 4 on a 11-point numeric rating scale at the time of screening
- Pain classified as at level radicular pain (ALRP), at level central pain (ALCP) or below level central pain (BLCP).
- Pain that is present regularly for at least 3 months prior to enrollment, in spite of medication or other pain treatment. This pain can be paroxysmal in nature (attacks of pain).
- Ability to understand instructions and reliably provide pain assessments
- Willingness to stop current opioid medications, if any
- If a female with childbearing potential, using an approved method of birth control (intrauterine device (IUD), barrier protection, a contraceptive implantation system or injection (Norplant® or Depo-Provera®), oral contraceptive pills, or celibacy)
Who cannot join
- A known sensitivity to opioids
- A history of substance or alcohol abuse within the past 2 years
- A need for elective surgery involving preoperative or postoperative analgesics or anesthetics during the study period
- Other chronic pain that cannot be differentiated from ALCP, ALRP, or BLCP
- A history of active cancer, excluding basal carcinoma of the skin, in the past 3 years
- Serum creatinine levels >= 2.5 mg/dl or hepatic (liver) dysfunction with serum ALT, AST, GGT, or total bilirubin >= 3 times the upper limit of normal
- Participation in any drug study in the last three months
- Currently pregnant or breastfeeding
Trial locations and contacts
1 site in 1 country.
United States1 site
Mount Sinai School of Medicine
New York, New York, 10029
About this study
We would like to learn if a medicine called "modified-release morphine sulfate" (Avinza) helps reduce Spinal Cord Injury (SCI)-related pain that has lasted a long time. "Modified-release" means that the medicine in the capsules is slowly released to the body, instead of being released all at once. Avinza is approved by the Food and Drug Administration for the treatment of pain, but we do not know how effective Avinza is in reducing SCI-related pain.
Read the detailed description
Neuropathic pain occurs as a result of damage to neural tissue either in the peripheral or in the central nervous system. Three types of neuropathic pain after SCI are especially difficult to treat: at level central pain (ALCP), at level radicular pain (ALRP), and below level central pain (BLCP). Various analgesic medications with distinct mechanisms and sites of action are currently used in clinical practice for treatment of neuropathic pain after SCI, including antidepressants, anticonvulsants, nonsteroidal anti-inflammatory drugs (NSAIDs), and opioids. These analgesic medications, when evaluated in animal models of SCI pain and in the treatment of other neuropathic pain states, have been shown to have only modest pain reducing effect. This modest effect is seen clinically as the majority of persons with SCI receiving these drugs continue to experience pain, which is severe and disabling in one third of cases.
This study proposes to examine the efficacy of oral modified release morphine in reducing pain in persons with neuropathic pain after SCI who have not adequately responded to other oral pharmacologic, psychologic, or physical interventions. Only subjects who have failed prior pain treatment regimes will be enrolled. Failure of pain regimen is defined as the presence of pain in spite of medication(s) or other pain treatment, such as biofeedback or other psychological or physical therapy interventions prescribed by a physician.
The following hypothesis will be tested: morphine, when added to non-opioid medications, is more effective than placebo in reducing pain and increasing activity and subjective well-being, in persons with ALCP, ALRP and BLCP. In order to test this hypothesis, a randomized, double blind, placebo-controlled, two period cross-over trial is proposed, during which subjects with ALCP, ALRP, and BLCP will receive daily placebo or modified release morphine while being closely monitored and assessed for: (1) adverse effects, (2) quality and intensity of pain, (3) intensity of allodynia and hyperalgesia, and (4) activity levels and well-being.
All subjects whether assigned to the placebo or active drug will be able to continue any previously prescribed or non-prescribed (over-the-counter) non-opioid medication that has been taken on a regular basis, without dose change, for at least three weeks prior to study entry. These medications may include but are not limited to the analgesics: acetaminophen and any non-steroidal anti-inflammatory drugs; local anesthetics- topical patches such as the lidocaine patch or otherwise; and adjuvant pain medications of the anti-depressant or anticonvulsant classes. Subjects will not be allowed to take any opioid medication, including non-opioid-opioid combination analgesics, other than the study drug for the duration of the study.
- Conditions
- Neuropathic Pain, Spinal Cord Injury
- Being tested
- Modified-release morphine, Placebo
- Keywords
- Morphine, Chronic Pain, Spinal Cord Injury, Neuropathic Pain
- Medical subject headings
- Neuralgia, Spinal Cord Injuries, Chronic Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Modified-release morphineDrug
Also called Modified-release morphine sulfate
During the first three weeks of each treatment (drug or placebo), the dose will be escalated toward a maximally tolerated dose or a dose sufficient to eliminate pain (up to a ceiling dose of 120 mg), whichever is reached first. During the entire fourth and fifth week of each period, subjects will receive their maximally tolerated dose of study medication. During the sixth and seventh weeks, they will undergo a seven-day dose tapering and a seven-day complete washout of the study drug.
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Modified-release morphine then Placebo | Active comparator | up to a ceiling dose of 120 mg Receives: Drug: Modified-release morphine; Drug: Placebo |
| Placebo then modified-release morphine | Placebo comparator | Matching placebo Receives: Drug: Modified-release morphine; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pain severity
Pain severity rated using a 0-10 Numeric Rating Scale (NRS)
Measured: Average of daily ratings over 14 days
Secondary outcomes (10)
Short McGill Pain Questionnaire (modified) (SF-McGill)
Measured: up to 14 weeks
Opioids cognitive effects scale
Measured: up to 14 weeks
Patient Generated Index for activity (PGI)
Measured: up to 14 weeks
Daily number of attacks of paroxysmal pain
Measured: up to 14 weeks
Quantitative sensory testing
Allodynia, hyperalgesia, and temporal summation (determined using quantitative sensory testing)
Measured: up to 14 weeks
Subject global impression of change
Measured: up to 14 weeks
Short-Form 36 (SF-36)
Measured: up to 14 weeks
Positive And Negative Affect Schedule (PANAS)
Measured: up to 14 weeks
Brief Patient Health Questionnaire (PHQ-9)
Measured: up to 14 weeks
Multidimensional Pain Inventory Life Interference subscale (MPI-LIS)
Measured: up to 14 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jun 2007 (estimated)
- Study startJul 2007
- Primary completionJul 2013
- Study completionJul 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neuropathic PainStudies of the same condition, open and under way.
- More trials run by Icahn School of Medicine at Mount SinaiThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Icahn School of Medicine at Mount Sinai
- Sponsor type
- University, hospital or other
- Collaborators
- U.S. Department of Education
- Responsible party
- Principal investigator, Thomas N. Bryce, Icahn School of Medicine at Mount Sinai
- Investigators
- Thomas Bryce, MD, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00488969
- Sponsor's protocol ID
- H133N060027
- Other IDs
- GCO # 90-135
- Status last verified
- Mar 2016
- First submitted
- 19 Jun 2007
- Last updated
- 22 Mar 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effectiveness of Controlled-Release Morphine for Chronic Neuropathic Pain After Spinal Cord Injury
- ClinicalTrials.gov ID
- NCT00488969
- Acronym / sponsor ID
- H133N060027
- Conditions
- Neuropathic Pain, Spinal Cord Injury
- Keywords
- Morphine, Chronic Pain, Spinal Cord Injury, Neuropathic Pain
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Icahn School of Medicine at Mount SinaiUniversity, hospital or other
- Collaborators
- U.S. Department of Education
- Study start
- Jul 2007
- Primary completion
- Jul 2013 (actual)
- Study completion
- Jul 2013 (actual)
- First posted
- 20 Jun 2007 (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.
We would like to learn if a medicine called "modified-release morphine sulfate" (Avinza) helps reduce Spinal Cord Injury (SCI)-related pain that has lasted a long time. "Modified-release" means that the medicine in the capsules is slowly released to the body, instead of being released all at once. Avinza is approved by the Food and Drug Administration for the treatment of pain, but we do not know how effective Avinza is in reducing SCI-related pain.
Detailed description
Neuropathic pain occurs as a result of damage to neural tissue either in the peripheral or in the central nervous system. Three types of neuropathic pain after SCI are especially difficult to treat: at level central pain (ALCP), at level radicular pain (ALRP), and below level central pain (BLCP). Various analgesic medications with distinct mechanisms and sites of action are currently used in clinical practice for treatment of neuropathic pain after SCI, including antidepressants, anticonvulsants, nonsteroidal anti-inflammatory drugs (NSAIDs), and opioids. These analgesic medications, when evaluated in animal models of SCI pain and in the treatment of other neuropathic pain states, have been shown to have only modest pain reducing effect. This modest effect is seen clinically as the majority of persons with SCI receiving these drugs continue to experience pain, which is severe and disabling in one third of cases.
This study proposes to examine the efficacy of oral modified release morphine in reducing pain in persons with neuropathic pain after SCI who have not adequately responded to other oral pharmacologic, psychologic, or physical interventions. Only subjects who have failed prior pain treatment regimes will be enrolled. Failure of pain regimen is defined as the presence of pain in spite of medication(s) or other pain treatment, such as biofeedback or other psychological or physical therapy interventions prescribed by a physician.
The following hypothesis will be tested: morphine, when added to non-opioid medications, is more effective than placebo in reducing pain and increasing activity and subjective well-being, in persons with ALCP, ALRP and BLCP. In order to test this hypothesis, a randomized, double blind, placebo-controlled, two period cross-over trial is proposed, during which subjects with ALCP, ALRP, and BLCP will receive daily placebo or modified release morphine while being closely monitored and assessed for: (1) adverse effects, (2) quality and intensity of pain, (3) intensity of allodynia and hyperalgesia, and (4) activity levels and well-being.
All subjects whether assigned to the placebo or active drug will be able to continue any previously prescribed or non-prescribed (over-the-counter) non-opioid medication that has been taken on a regular basis, without dose change, for at least three weeks prior to study entry. These medications may include but are not limited to the analgesics: acetaminophen and any non-steroidal anti-inflammatory drugs; local anesthetics- topical patches such as the lidocaine patch or otherwise; and adjuvant pain medications of the anti-depressant or anticonvulsant classes. Subjects will not be allowed to take any opioid medication, including non-opioid-opioid combination analgesics, other than the study drug for the duration of the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Modified-release morphine then Placebo | Active comparator | Drug: Modified-release morphine, Drug: Placeboup to a ceiling dose of 120 mg |
| Placebo then modified-release morphine | Placebo comparator | Drug: Modified-release morphine, Drug: PlaceboMatching placebo |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age 18 - 65
- Diagnosis of traumatic spinal cord injury
- Neuropathic pain (pain related to the nervous system) rated at least 4 on a 11-point numeric rating scale at the time of screening
- Pain classified as at level radicular pain (ALRP), at level central pain (ALCP) or below level central pain (BLCP).
- Pain that is present regularly for at least 3 months prior to enrollment, in spite of medication or other pain treatment. This pain can be paroxysmal in nature (attacks of pain).
Key exclusion criteria (8 listed)
- A known sensitivity to opioids
- A history of substance or alcohol abuse within the past 2 years
- A need for elective surgery involving preoperative or postoperative analgesics or anesthetics during the study period
- Other chronic pain that cannot be differentiated from ALCP, ALRP, or BLCP
- A history of active cancer, excluding basal carcinoma of the skin, in the past 3 years
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 |
|---|---|---|
| Modified-release morphineAlso: Modified-release morphine sulfateDuring the first three weeks of each treatment (drug or placebo), the dose will be escalated toward a maximally tolerated dose or a dose sufficient to eliminate pain (up to a ceiling dose of 120 mg), whichever is reached first. During the entire fourth and fifth week of each period, subjects will receive their maximally tolerated dose of study medication. During the sixth and seventh weeks, they will undergo a seven-day dose tapering and a seven-day complete washout of the study drug. | Drug | Modified-release morphine then Placebo, Placebo then modified-release morphine |
| Placebo | Drug | Modified-release morphine then Placebo, Placebo then modified-release morphine |
Primary outcome
Pain severity
Time frame: Average of daily ratings over 14 days
Pain severity rated using a 0-10 Numeric Rating Scale (NRS)
10 secondary outcomes
Short McGill Pain Questionnaire (modified) (SF-McGill)
Time frame: up to 14 weeks
Opioids cognitive effects scale
Time frame: up to 14 weeks
Patient Generated Index for activity (PGI)
Time frame: up to 14 weeks
Daily number of attacks of paroxysmal pain
Time frame: up to 14 weeks
Quantitative sensory testing
Time frame: up to 14 weeks
Subject global impression of change
Time frame: up to 14 weeks
Short-Form 36 (SF-36)
Time frame: up to 14 weeks
Positive And Negative Affect Schedule (PANAS)
Time frame: up to 14 weeks
Brief Patient Health Questionnaire (PHQ-9)
Time frame: up to 14 weeks
Multidimensional Pain Inventory Life Interference subscale (MPI-LIS)
Time frame: up to 14 weeks
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 22 Mar 2016.
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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.
Thomas Bryce, MD principal investigator
Icahn School of Medicine at Mount Sinai
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Modified-release morphine in people with Neuropathic Pain and Spinal Cord Injury, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.
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 8 inclusion and 8 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 22 Mar 2016. 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 United States. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Pain severity (time frame: Average of daily ratings over 14 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 22 Mar 2016.