Opioid-related DisordersPhase 2NCT00460239
Buprenorphine's Dose Response Curve
A Phase 2 study testing Buprenorphine and Morphine in people with Opioid-related Disorders, run by Johns Hopkins University at 1 site in United States.
Trial summary
This is a residential study that looks at the effects of buprenorphine in persons who abuse but are not dependent on opioids. Animal studies show that very high doses of buprenorphine produce less effects than mid-range doses. This suggests that buprenorphine can be a very safe medication. Read more about this study
- Who is it for?
- Ages 21 to 55 years
- Conditions the study is for
- Opioid-related Disorders
- What is being tested?
- Buprenorphine and Morphine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2007to Jul 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 21 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 1. current opioid abuse but not physically dependent on opioids
Who cannot join
- evidence of significant medical (e.g., insulin dependent diabetes) or psychiatric (e.g., schizophrenia) illness
- anemia defined as a hematocrit less than 30%
- females are required to provide a negative pregnancy test prior to study participation
- baseline electrocardiogram (ECG) showing prolongation of the corrected QT interval (QTc)
- current significant alcohol or sedative/hypnotic drug use
- Forced expiratory volume at one second (FEV1) of less than 50% at the time of screening
- applicants seeking treatment for their substance abuse will not be admitted to the study, and should be provided information about treatment services available
Trial locations and contacts
1 site in 1 country.
United States1 site
Johns Hopkins University (BPRU) Bayview Campus
Baltimore, Maryland, 21224
About this study
Official title: Evaluation of Opioid Antagonist Activity in Humans
This is a residential study that looks at the effects of buprenorphine in persons who abuse but are not dependent on opioids. Animal studies show that very high doses of buprenorphine produce less effects than mid-range doses. This suggests that buprenorphine can be a very safe medication. However, no studies in humans have tested higher doses in a similar way. The goal of this study is to show the effects of single doses of buprenorphine, across a range of doses, in persons who are not physically dependent on opioids (but do abuse opioids).
Read the detailed description
Preclinical studies have demonstrated for a variety of measures that buprenorphine has a bell-shaped dose response curve. However, human studies with buprenorphine have not shown such an effect, although controlled studies have generally not tested higher acute doses of buprenorphine. Current clinical recommendations generally place an upper limit of daily buprenorphine dosing at 32 mg of sublingual tablets, although considerably higher acute doses have been administered to humans (primarily in clinical studies of less than daily dosing). Determining the relationship between higher doses of buprenorphine in humans and effects produced would be valuable; it would be scientifically interesting to demonstrate a bell-shaped curve in humans, and it would help guide clinical practice (for example, with respect to dosing, safety, and side effect considerations. The purpose of this study is to characterize the dose response curve for buprenorphine in humans, utilizing acute single doses of parenteral buprenorphine.
- Conditions
- Opioid-related Disorders
- Being tested
- Buprenorphine, Morphine, Placebo
- Keywords
- Opioid addiction, Opioid dependence, Buprenorphine
- Medical subject headings
- Opioid-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BuprenorphineDrug
Intramuscular, doses (8, 16, 32, 48, 60 mg) are blind; administered up to 1-2 times per week.
MorphineDrug
Intramuscular; up to 1-2 times per week; doses (15, 30 mg) double blind
PlaceboDrug
Intramuscular; double blind; once per week
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Experimental | All participants are randomly assigned to receive an order of the 8 study drugs/doses (placebo, 2 doses of morphine, 5 doses of buprenorphine). Receives: Drug: Placebo |
| Morphine 15 | Experimental | All participants are randomly assigned to receive an order of the 8 study drugs/doses (placebo, 2 doses of morphine, 5 doses of buprenorphine). Receives: Drug: Morphine |
| Morphine 30 | Experimental | All participants are randomly assigned to receive an order of the 8 study drugs/doses (placebo, 2 doses of morphine, 5 doses of buprenorphine). Receives: Drug: Morphine |
| Buprenorphine 8 | Experimental | All participants are randomly assigned to receive an order of the 8 study drugs/doses (placebo, 2 doses of morphine, 5 doses of buprenorphine). Receives: Drug: Buprenorphine |
| Buprenorphine 16 | Experimental | All participants are randomly assigned to receive an order of the 8 study drugs/doses (placebo, 2 doses of morphine, 5 doses of buprenorphine). Receives: Drug: Buprenorphine |
| Buprenorphine 32 | Experimental | All participants are randomly assigned to receive an order of the 8 study drugs/doses (placebo, 2 doses of morphine, 5 doses of buprenorphine). Receives: Drug: Buprenorphine |
| Buprenorphine 48 | Experimental | All participants are randomly assigned to receive an order of the 8 study drugs/doses (placebo, 2 doses of morphine, 5 doses of buprenorphine). Receives: Drug: Buprenorphine |
| Buprenorphine 60 | Experimental | All participants are randomly assigned to receive an order of the 8 study drugs/doses (placebo, 2 doses of morphine, 5 doses of buprenorphine). Receives: Drug: Buprenorphine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Peak Change From Baseline in Drug Effect Assessed by Visual Analog Scale (VAS)
Opioid agonist effects measured by peak change from baseline drug effect visual analog scale. Scores range from 0 (not all all) to 100 (extremely); higher scores indicate a stronger drug effect.
Measured: Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)
Psychomotor/Cognitive Performance Effects Assessed by Digit Symbol Substitution Test (DSST)
Digit Symbol Substitution Test (DSST) is a sub-test within the Wechsler Adult Intelligence Scale and is frequently used to assess psychomotor performance changes associated with drug effects. The higher the percent correct on this measure the better the performance.
Measured: Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)
Psychomotor/Cognitive Performance Effects Assessed by Trails B
The Trails B task specifically measures set shifting and executive functioning within the Trail-Making Test. Part B consists of 25 circles distributed over a sheet of paper. Participants are asked to connect the circles in an ascending pattern, alternating between numbers and letters (i.e., 1-A-2-B-3-C, etc.). Results are reported as the number of seconds required to complete the task; therefore, higher scores reveal greater impairment.
Measured: Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)
Physiologic Effects as Assessed by Blood Pressure
Measured: Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)
Physiologic Effects as Assessed by Heart Rate
Measured: Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)
Physiologic Effects as Assessed by Body Temperature
Measured: Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)
Physiologic Effects as Assessed by Oxygen Saturation
Measured: Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)
Physiologic Effects as Assessed by Pupil Diameter
Measured: Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2007 (estimated)
- Study startJan 2007
- Primary completionJul 2009
- Study completionJul 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Opioid-related DisordersStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe 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
- Single group
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Sponsor
- Investigators
- Eric C Strain, M.D., Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00460239
- Sponsor's protocol ID
- NIDA-08045-8
- Other IDs
- 5R01DA008045-08, R01DA008045, DPMCDA
- Status last verified
- Jan 2017
- First submitted
- 11 Apr 2007
- Last updated
- 3 Mar 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Opioid Antagonist Activity in Humans
- ClinicalTrials.gov ID
- NCT00460239
- Acronym / sponsor ID
- NIDA-08045-8
- Conditions
- Opioid-related Disorders
- Keywords
- Opioid addiction, Opioid dependence, Buprenorphine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- Jan 2007
- Primary completion
- Jul 2009 (actual)
- Study completion
- Jul 2009 (actual)
- First posted
- 13 Apr 2007 (estimated)
- Results
- Posted 3 Mar 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a residential study that looks at the effects of buprenorphine in persons who abuse but are not dependent on opioids. Animal studies show that very high doses of buprenorphine produce less effects than mid-range doses. This suggests that buprenorphine can be a very safe medication. However, no studies in humans have tested higher doses in a similar way. The goal of this study is to show the effects of single doses of buprenorphine, across a range of doses, in persons who are not physically dependent on opioids (but do abuse opioids).
Detailed description
Preclinical studies have demonstrated for a variety of measures that buprenorphine has a bell-shaped dose response curve. However, human studies with buprenorphine have not shown such an effect, although controlled studies have generally not tested higher acute doses of buprenorphine. Current clinical recommendations generally place an upper limit of daily buprenorphine dosing at 32 mg of sublingual tablets, although considerably higher acute doses have been administered to humans (primarily in clinical studies of less than daily dosing). Determining the relationship between higher doses of buprenorphine in humans and effects produced would be valuable; it would be scientifically interesting to demonstrate a bell-shaped curve in humans, and it would help guide clinical practice (for example, with respect to dosing, safety, and side effect considerations. The purpose of this study is to characterize the dose response curve for buprenorphine in humans, utilizing acute single doses of parenteral buprenorphine.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Placebo | Experimental | Drug: PlaceboAll participants are randomly assigned to receive an order of the 8 study drugs/doses (placebo, 2 doses of morphine, 5 doses of buprenorphine). |
| Morphine 15 | Experimental | Drug: MorphineAll participants are randomly assigned to receive an order of the 8 study drugs/doses (placebo, 2 doses of morphine, 5 doses of buprenorphine). |
| Morphine 30 | Experimental | Drug: MorphineAll participants are randomly assigned to receive an order of the 8 study drugs/doses (placebo, 2 doses of morphine, 5 doses of buprenorphine). |
| Buprenorphine 8 | Experimental | Drug: BuprenorphineAll participants are randomly assigned to receive an order of the 8 study drugs/doses (placebo, 2 doses of morphine, 5 doses of buprenorphine). |
| Buprenorphine 16 | Experimental | Drug: BuprenorphineAll participants are randomly assigned to receive an order of the 8 study drugs/doses (placebo, 2 doses of morphine, 5 doses of buprenorphine). |
| Buprenorphine 32 | Experimental | Drug: BuprenorphineAll participants are randomly assigned to receive an order of the 8 study drugs/doses (placebo, 2 doses of morphine, 5 doses of buprenorphine). |
| Buprenorphine 48 | Experimental | Drug: BuprenorphineAll participants are randomly assigned to receive an order of the 8 study drugs/doses (placebo, 2 doses of morphine, 5 doses of buprenorphine). |
| Buprenorphine 60 | Experimental | Drug: BuprenorphineAll participants are randomly assigned to receive an order of the 8 study drugs/doses (placebo, 2 doses of morphine, 5 doses of buprenorphine). |
Who may qualify
- Ages
- 21 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- 1. current opioid abuse but not physically dependent on opioids
Key exclusion criteria (7 listed)
- evidence of significant medical (e.g., insulin dependent diabetes) or psychiatric (e.g., schizophrenia) illness
- anemia defined as a hematocrit less than 30%
- females are required to provide a negative pregnancy test prior to study participation
- baseline electrocardiogram (ECG) showing prolongation of the corrected QT interval (QTc)
- current significant alcohol or sedative/hypnotic drug use
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 |
|---|---|---|
| BuprenorphineIntramuscular, doses (8, 16, 32, 48, 60 mg) are blind; administered up to 1-2 times per week. | Drug | Buprenorphine 16, Buprenorphine 32, Buprenorphine 48, Buprenorphine 60, Buprenorphine 8 |
| MorphineIntramuscular; up to 1-2 times per week; doses (15, 30 mg) double blind | Drug | Morphine 15, Morphine 30 |
| PlaceboIntramuscular; double blind; once per week | Drug | Placebo |
Primary outcome
Peak Change From Baseline in Drug Effect Assessed by Visual Analog Scale (VAS)
Time frame: Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)
Opioid agonist effects measured by peak change from baseline drug effect visual analog scale. Scores range from 0 (not all all) to 100 (extremely); higher scores indicate a stronger drug effect.
Psychomotor/Cognitive Performance Effects Assessed by Digit Symbol Substitution Test (DSST)
Time frame: Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)
Digit Symbol Substitution Test (DSST) is a sub-test within the Wechsler Adult Intelligence Scale and is frequently used to assess psychomotor performance changes associated with drug effects. The higher the percent correct on this measure the better the performance.
Psychomotor/Cognitive Performance Effects Assessed by Trails B
Time frame: Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)
The Trails B task specifically measures set shifting and executive functioning within the Trail-Making Test. Part B consists of 25 circles distributed over a sheet of paper. Participants are asked to connect the circles in an ascending pattern, alternating between numbers and letters (i.e., 1-A-2-B-3-C, etc.). Results are reported as the number of seconds required to complete the task; therefore, higher scores reveal greater impairment.
Physiologic Effects as Assessed by Blood Pressure
Time frame: Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)
Physiologic Effects as Assessed by Heart Rate
Time frame: Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)
Physiologic Effects as Assessed by Body Temperature
Time frame: Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)
Physiologic Effects as Assessed by Oxygen Saturation
Time frame: Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)
Physiologic Effects as Assessed by Pupil Diameter
Time frame: Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Mar 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Eric C Strain, M.D. principal investigator
Johns Hopkins University
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 Buprenorphine and Morphine in people with Opioid-related Disorders, run by Johns Hopkins University 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 1 inclusion and 7 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 3 Mar 2017. 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.
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?
Yes. Results are posted in the registry (first posted 3 Mar 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Peak Change From Baseline in Drug Effect Assessed by Visual Analog Scale (VAS) (time frame: Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)). The study lists 8 primary outcomes in all. 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 3 Mar 2017.