Buprenorphine's Dose Response Curve

January 11, 2017 updated by: Johns Hopkins University

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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
12

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21224
        • Johns Hopkins University (BPRU) Bayview Campus

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

21 years to 55 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

1. current opioid abuse but not physically dependent on opioids

Exclusion Criteria:

  1. evidence of significant medical (e.g., insulin dependent diabetes) or psychiatric (e.g., schizophrenia) illness
  2. anemia defined as a hematocrit less than 30%
  3. females are required to provide a negative pregnancy test prior to study participation
  4. baseline electrocardiogram (ECG) showing prolongation of the corrected QT interval (QTc)
  5. current significant alcohol or sedative/hypnotic drug use
  6. Forced expiratory volume at one second (FEV1) of less than 50% at the time of screening
  7. applicants seeking treatment for their substance abuse will not be admitted to the study, and should be provided information about treatment services available

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Placebo
All participants are randomly assigned to receive an order of the 8 study drugs/doses (placebo, 2 doses of morphine, 5 doses of buprenorphine).
Drug: Placebo
Intramuscular; double blind; once per week
Experimental: Morphine 15
All participants are randomly assigned to receive an order of the 8 study drugs/doses (placebo, 2 doses of morphine, 5 doses of buprenorphine).
Drug: Morphine
Intramuscular; up to 1-2 times per week; doses (15, 30 mg) double blind
Experimental: Morphine 30
All participants are randomly assigned to receive an order of the 8 study drugs/doses (placebo, 2 doses of morphine, 5 doses of buprenorphine).
Drug: Morphine
Intramuscular; up to 1-2 times per week; doses (15, 30 mg) double blind
Experimental: Buprenorphine 8
All participants are randomly assigned to receive an order of the 8 study drugs/doses (placebo, 2 doses of morphine, 5 doses of buprenorphine).
Drug: Buprenorphine
Intramuscular, doses (8, 16, 32, 48, 60 mg) are blind; administered up to 1-2 times per week.
Experimental: Buprenorphine 16
All participants are randomly assigned to receive an order of the 8 study drugs/doses (placebo, 2 doses of morphine, 5 doses of buprenorphine).
Drug: Buprenorphine
Intramuscular, doses (8, 16, 32, 48, 60 mg) are blind; administered up to 1-2 times per week.
Experimental: Buprenorphine 32
All participants are randomly assigned to receive an order of the 8 study drugs/doses (placebo, 2 doses of morphine, 5 doses of buprenorphine).
Drug: Buprenorphine
Intramuscular, doses (8, 16, 32, 48, 60 mg) are blind; administered up to 1-2 times per week.
Experimental: Buprenorphine 48
All participants are randomly assigned to receive an order of the 8 study drugs/doses (placebo, 2 doses of morphine, 5 doses of buprenorphine).
Drug: Buprenorphine
Intramuscular, doses (8, 16, 32, 48, 60 mg) are blind; administered up to 1-2 times per week.
Experimental: Buprenorphine 60
All participants are randomly assigned to receive an order of the 8 study drugs/doses (placebo, 2 doses of morphine, 5 doses of buprenorphine).
Drug: Buprenorphine
Intramuscular, doses (8, 16, 32, 48, 60 mg) are blind; administered up to 1-2 times per week.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
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)
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.
Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)
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.
Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)
Physiologic Effects as Assessed by Blood Pressure
Time Frame: Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)
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)
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)
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)
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)
Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Johns Hopkins University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute on Drug Abuse (NIDA)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Eric C Strain, M.D., Johns Hopkins University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2007

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2009

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2009

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 11, 2007

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 11, 2007

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 13, 2007

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 3, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 11, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • NIDA-08045-8
  • DPMCDA (Other Identifier: NIDA)
  • 5R01DA008045-08 (U.S. NIH Grant/Contract)
  • R01DA008045 (U.S. NIH Grant/Contract)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Opioid-related Disorders

Clinical Trials on Placebo

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings