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Buprenorphine's Dose Response Curve

This study has been completed.
Sponsor:
Collaborator:
National Institute on Drug Abuse (NIDA)
Information provided by (Responsible Party):
Johns Hopkins University
ClinicalTrials.gov Identifier:
NCT00460239
First received: April 11, 2007
Last updated: January 11, 2017
Last verified: January 2017
  Purpose
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).

Condition Intervention Phase
Opioid-related Disorders
Drug: Buprenorphine
Drug: Morphine
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double Blind (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Evaluation of Opioid Antagonist Activity in Humans

Resource links provided by NLM:


Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:
  • 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) ]

Enrollment: 12
Study Start Date: January 2007
Study Completion Date: July 2009
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.
  Eligibility

Ages Eligible for Study:   21 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00460239

Locations
United States, Maryland
Johns Hopkins University (BPRU) Bayview Campus
Baltimore, Maryland, United States, 21224
Sponsors and Collaborators
Johns Hopkins University
National Institute on Drug Abuse (NIDA)
Investigators
Principal Investigator: Eric C Strain, M.D. Johns Hopkins University
  More Information

Responsible Party: Johns Hopkins University
ClinicalTrials.gov Identifier: NCT00460239     History of Changes
Other Study ID Numbers: NIDA-08045-8
5R01DA008045-08 ( US NIH Grant/Contract Award Number )
R01DA008045 ( US NIH Grant/Contract Award Number )
DPMCDA ( Other Identifier: NIDA )
Study First Received: April 11, 2007
Results First Received: August 18, 2012
Last Updated: January 11, 2017

Keywords provided by Johns Hopkins University:
Opioid addiction
Opioid dependence
Buprenorphine

Additional relevant MeSH terms:
Opioid-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Morphine
Analgesics, Opioid
Buprenorphine
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Narcotic Antagonists

ClinicalTrials.gov processed this record on April 24, 2017