PainNCT00679458
Randomized, Double-Blind Cross-Over Trial Of Buprenorphine and Low-Dose Naloxone Versus Buprenorphine
A study testing buprenorphine and low-dose naloxone and buprenorphine alone in people with Pain, run by University of California, Los Angeles at 1 site in United States.
Trial summary
This study compares two medications for analgesic potency and side effects in a sample of individuals with moderate pain. After screening, eligible participants will be randomly assigned to begin blinded treatment with one of two medications. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pain
- What is being tested?
- buprenorphine and low-dose naloxone and buprenorphine alone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2008to Nov 2009
- Phase
- Interventional
- 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
- Participants must meet all of the following:
- 18 years of age or older
- Have chronic pain that is not related to cancer, defined as pain expected to last a month or more,(i.e. musculoskeletal pain or neuropathic pain)
- Report pain of moderate to moderately-severe intensity during the week prior to the baseline screening visit (a score greater than or equal to 4 for average pain in the past week on the 0-10 point Pain Intensity-Numerical Rating Scale)
- Have used prescription opioid and/or non-opioid analgesics for the pain on at least 15 of the 30 days prior to the initial baseline/screening visit and have clearance from their prescribing physician to discontinue all non-study-related opiates during study participation
- Willing and able to comply with study procedures
- Willing and able to provide written consent
- If female, not pregnant or lactating and willing to use an acceptable method of birth control (e.g., condoms, IUD, birth control pills, or Depo-Provera)
Who cannot join
- Participants must not meet any of the following:
- Have a history of dependence on opiates, stimulants, alcohol, or benzodiazepines, as defined by DSM-IV criteria, within the past year (physical dependence on prescribed opioid analgesics is allowed but opioid dependence according to DSM-IV, i.e. opioid addiction, is not)
- Use of any illicit or recreational drugs (heroin, cocaine, methamphetamine, marijuana, etc.) ; or use of any long-acting opioid (i.e., methadone) in the 30 days prior to the initial screening visit
- Concomitant use of medications that are inhibitors of CYP3A4 (e.g., azole antifungals, macrolide antibiotics, and HIV protease inhibitors), or medications that induce CYP3A4 activity (e.g., anticonvulsants and rifampin) that may alter the metabolism of buprenorphine
- Have a medical condition that, in the study physician's judgment, may interfere with safe study participation for the individual study candidate. Because medical conditions may differ in terms of safe participation on an individual basis, this criterion must be based on a physician's determination after a medical history, exam, and lab tests and may also involve consultation with a study candidate's primacy care physician. Some examples of medical conditions that may be exclusionary for a particular individual, however include active tuberculosis, unstable and/or significant cardiovascular or liver disease, unstable diabetes (i.e., glycosylated hemoglobin A1C of 12%), uncontrolled HIV infection, altered renal function (serum creatinine males and females:>3x upper limit of normal) or clinically significant elevated liver enzymes (ALT or AST greater than 3x the upper limit of normal)
- Have a current neurological disorder (e.g., organic brain disease, dementia) or current major psychiatric disorder (e.g., schizophrenia, bipolar illness, or PTSD) that would make study agent compliance difficult, that would compromise informed consent, or that would jeopardize safety
Show all 12Show fewer
- Have a history of suicide attempts in the past 180 days and/or current serious suicidal risk
- Have any history of a seizure disorder
- Have a known allergy or sensitivity to buprenorphine or naloxone
- Receiving long-acting opioids, such as methadone, LAAM, or sustained release morphine, for treatment of pain (due to problems with initiating buprenorphine treatment among patients receiving long-acting opioids)
- Have recent surgery or a major medical procedure that could potentially interfere with study participation
- Any other circumstances that, in the opinion of the investigators, would interfere with study participation
Trial locations and contacts
1 site in 1 country.
United States1 site
UCLA Integrated Substance Abuse Programs Outpatient Research Center
Los Angeles, California, 90025'
About this study
Official title: A Randomized, Double-blind, Cross-over Trial Comparing the Analgesic Potency and Side Effects of Buprenorphine and Ultra-low-dose Naloxone to Buprenorphine Alone
This study compares two medications for analgesic potency and side effects in a sample of individuals with moderate pain. After screening, eligible participants will be randomly assigned to begin blinded treatment with one of two medications. Participants receive 5 daily doses of medication (no more than 2 days between each dose) followed by crossover to the opposite treatment condition for 5 additional daily doses. Each study day, participants will provide a daily pain assessment, receive administration of study medication, and will then be monitored and assessed for pain and side effects over 6 hours.
Read the detailed description
Treatment of chronic pain typically relies on the effectiveness of opioid analgesics, however, side effects and the potential for users to develop tolerance and addiction may make physicians hesitant to prescribe them. The development of opioid analgesics with fewer side effects and decreased potential tolerance and addiction would increase the ability to safely and effectively treat pain. This study will determine whether the addition of an ultra-low dose of naloxone, an opioid antagonist, to buprenorphine, an opioid analgesic pain medication, increases the analgesic potency and reduces side effects compared to buprenorphine alone. Low doses of naloxone added to buprenorphine have been shown to increase the potency and reduce the side effects of buprenorphine in animal studies and in a human study with healthy volunteers. The current study aims to extend these findings by assessing the analgesic potency and side effects of a 15:1 ratio of buprenorphine to naloxone in a sample of 12 outpatient participants with moderate pain (4 or greater pain intensity) who are experienced with opioid analgesics. Participants will be randomly assigned to begin blinded treatment starting with one of two medication regimens: IV buprenorphine + ultra-low-dose naloxone or IV buprenorphine alone. Participants receive 5 daily doses of medication (no more than 2 days between each dose) followed by crossover to the opposite treatment condition for 5 additional daily doses. Each study day, participants will provide a daily pain assessment, receive administration of study medication, and will then be monitored and assessed for pain and side effects over the next six hours. Outcomes for the study include: (1) pain intensity as measured using the Brief Pain Inventory, pain intensity numerical rating scale, and the Beck Depression Inventory, and (2) self-reported side effects/adverse events. After completion of study participation, participants will resume pre-study pain treatments with their own physician.
- Conditions
- Pain
- Being tested
- buprenorphine and low-dose naloxone, buprenorphine alone
- Keywords
- analgesia, pain, buprenorphine, opioid, naloxone
- Medical subject headings
- Pain, Agnosia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
buprenorphine and low-dose naloxoneDrug
each participant will be randomly assigned to order of study drug administration in a double-blind manner. Five doses of first study drug will be administered for 5 days, with each administration following the previous dose by not more than 2 days. Administration of the second study drug, buprenorphine only, will follow at least 2 days after the completion of the first study drug with the same administration criteria. Medication will be administered IV, and assessments will continue for 6 hours after administration. Study drugs include 1) buprenorphine 0.3mg and naloxone 0.02mg and, 2) buprenorphine 0.3mg.
buprenorphine aloneDrug
each participant will be randomly assigned to order of study drug administration in a double-blind manner. Five doses of first study drug will be administered for 5 days, with each administration following the previous dose by not more than 2 days. Administration of the second study drug will follow at least 2 days after the completion of the first study drug with the same administration criteria. Medication will be administered IV, and assessments will continue for 6 hours after administration. Study drugs include 1) buprenorphine 0.3mg and naloxone 0.02mg and, 2) buprenorphine 0.3mg.
| Study group | Role | What they receive |
|---|---|---|
| 1. | Experimental | Study drug: buprenorphine and ultra-low-dose naloxone Receives: Drug: buprenorphine and low-dose naloxone |
| 2. | Active comparator | Study drug: buprenorphine Receives: Drug: buprenorphine alone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pain intensity
Measured: After each dose of study drug
Secondary outcomes (1)
Self-reported side effects/adverse events
Measured: after each daily dose of study drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2008 (estimated)
- Study startSep 2008
- Primary completionNov 2009
- Study completionNov 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PainStudies of the same condition, open and under way.
- More trials run by University of California, Los AngelesThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of California, Los Angeles
- Sponsor type
- University, hospital or other
- Collaborators
- Indivior Inc.
- Investigators
- Walter Ling, M.D., Principal investigator, UCLA Integrated Substance Abuse Programs
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00679458
- Sponsor's protocol ID
- 07-06-005
- Status last verified
- Nov 2009
- First submitted
- 14 May 2008
- Last updated
- 7 Jan 2010
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Jan 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Cross-over Trial Comparing the Analgesic Potency and Side Effects of Buprenorphine and Ultra-low-dose Naloxone to Buprenorphine Alone
- ClinicalTrials.gov ID
- NCT00679458
- Acronym / sponsor ID
- 07-06-005
- Conditions
- Pain
- Keywords
- analgesia, pain, buprenorphine, opioid, naloxone
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- University of California, Los AngelesUniversity, hospital or other
- Collaborators
- Indivior Inc.
- Study start
- Sep 2008
- Primary completion
- Nov 2009 (actual)
- Study completion
- Nov 2009 (actual)
- First posted
- 16 May 2008 (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.
This study compares two medications for analgesic potency and side effects in a sample of individuals with moderate pain. After screening, eligible participants will be randomly assigned to begin blinded treatment with one of two medications. Participants receive 5 daily doses of medication (no more than 2 days between each dose) followed by crossover to the opposite treatment condition for 5 additional daily doses. Each study day, participants will provide a daily pain assessment, receive administration of study medication, and will then be monitored and assessed for pain and side effects over 6 hours.
Detailed description
Treatment of chronic pain typically relies on the effectiveness of opioid analgesics, however, side effects and the potential for users to develop tolerance and addiction may make physicians hesitant to prescribe them. The development of opioid analgesics with fewer side effects and decreased potential tolerance and addiction would increase the ability to safely and effectively treat pain. This study will determine whether the addition of an ultra-low dose of naloxone, an opioid antagonist, to buprenorphine, an opioid analgesic pain medication, increases the analgesic potency and reduces side effects compared to buprenorphine alone. Low doses of naloxone added to buprenorphine have been shown to increase the potency and reduce the side effects of buprenorphine in animal studies and in a human study with healthy volunteers. The current study aims to extend these findings by assessing the analgesic potency and side effects of a 15:1 ratio of buprenorphine to naloxone in a sample of 12 outpatient participants with moderate pain (4 or greater pain intensity) who are experienced with opioid analgesics. Participants will be randomly assigned to begin blinded treatment starting with one of two medication regimens: IV buprenorphine + ultra-low-dose naloxone or IV buprenorphine alone. Participants receive 5 daily doses of medication (no more than 2 days between each dose) followed by crossover to the opposite treatment condition for 5 additional daily doses. Each study day, participants will provide a daily pain assessment, receive administration of study medication, and will then be monitored and assessed for pain and side effects over the next six hours. Outcomes for the study include: (1) pain intensity as measured using the Brief Pain Inventory, pain intensity numerical rating scale, and the Beck Depression Inventory, and (2) self-reported side effects/adverse events. After completion of study participation, participants will resume pre-study pain treatments with their own physician.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1. | Experimental | Drug: buprenorphine and low-dose naloxoneStudy drug: buprenorphine and ultra-low-dose naloxone |
| 2. | Active comparator | Drug: buprenorphine aloneStudy drug: buprenorphine |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 18 years of age or older
- Have chronic pain that is not related to cancer, defined as pain expected to last a month or more,(i.e. musculoskeletal pain or neuropathic pain)
- Report pain of moderate to moderately-severe intensity during the week prior to the baseline screening visit (a score greater than or equal to 4 for average pain in the past week on the 0-10 point Pain Intensity-Numerical Rating Scale)
- Have used prescription opioid and/or non-opioid analgesics for the pain on at least 15 of the 30 days prior to the initial baseline/screening visit and have clearance from their prescribing physician to discontinue all non-study-related opiates during study participation
- Willing and able to comply with study procedures
Key exclusion criteria (12 listed)
- Have a history of dependence on opiates, stimulants, alcohol, or benzodiazepines, as defined by DSM-IV criteria, within the past year (physical dependence on prescribed opioid analgesics is allowed but opioid dependence according to DSM-IV, i.e. opioid addiction, is not)
- Use of any illicit or recreational drugs (heroin, cocaine, methamphetamine, marijuana, etc.) ; or use of any long-acting opioid (i.e., methadone) in the 30 days prior to the initial screening visit
- Concomitant use of medications that are inhibitors of CYP3A4 (e.g., azole antifungals, macrolide antibiotics, and HIV protease inhibitors), or medications that induce CYP3A4 activity (e.g., anticonvulsants and rifampin) that may alter the metabolism of buprenorphine
- Have a medical condition that, in the study physician's judgment, may interfere with safe study participation for the individual study candidate. Because medical conditions may differ in terms of safe participation on an individual basis, this criterion must be based on a physician's determination after a medical history, exam, and lab tests and may also involve consultation with a study candidate's primacy care physician. Some examples of medical conditions that may be exclusionary for a particular individual, however include active tuberculosis, unstable and/or significant cardiovascular or liver disease, unstable diabetes (i.e., glycosylated hemoglobin A1C of 12%), uncontrolled HIV infection, altered renal function (serum creatinine males and females:>3x upper limit of normal) or clinically significant elevated liver enzymes (ALT or AST greater than 3x the upper limit of normal)
- Have a current neurological disorder (e.g., organic brain disease, dementia) or current major psychiatric disorder (e.g., schizophrenia, bipolar illness, or PTSD) that would make study agent compliance difficult, that would compromise informed consent, or that would jeopardize safety
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 |
|---|---|---|
| buprenorphine and low-dose naloxoneeach participant will be randomly assigned to order of study drug administration in a double-blind manner. Five doses of first study drug will be administered for 5 days, with each administration following the previous dose by not more than 2 days. Administration of the second study drug, buprenorphine only, will follow at least 2 days after the completion of the first study drug with the same administration criteria. Medication will be administered IV, and assessments will continue for 6 hours after administration. Study drugs include 1) buprenorphine 0.3mg and naloxone 0.02mg and, 2) buprenorphine 0.3mg. | Drug | 1. |
| buprenorphine aloneeach participant will be randomly assigned to order of study drug administration in a double-blind manner. Five doses of first study drug will be administered for 5 days, with each administration following the previous dose by not more than 2 days. Administration of the second study drug will follow at least 2 days after the completion of the first study drug with the same administration criteria. Medication will be administered IV, and assessments will continue for 6 hours after administration. Study drugs include 1) buprenorphine 0.3mg and naloxone 0.02mg and, 2) buprenorphine 0.3mg. | Drug | 2. |
Primary outcome
Pain intensity
Time frame: After each dose of study drug
1 secondary outcome
Self-reported side effects/adverse events
Time frame: after each daily dose of study drug
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 Jan 2010.
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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.
Walter Ling, M.D. principal investigator
UCLA Integrated Substance Abuse Programs
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing buprenorphine and low-dose naloxone and buprenorphine alone in people with Pain, run by University of California, Los Angeles 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 12 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 Jan 2010. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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 intensity (time frame: After each dose of study drug). 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 7 Jan 2010.