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Buprenorphine's Dose Response Curve

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified April 2012 by National Institute on Drug Abuse (NIDA).
Recruitment status was:  Active, not recruiting
Information provided by (Responsible Party):
Eric Strain, MD, Johns Hopkins University Identifier:
First received: April 11, 2007
Last updated: April 21, 2012
Last verified: April 2012
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: Crossover Assignment
Masking: Double Blind (Subject, 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 National Institute on Drug Abuse (NIDA):

Primary Outcome Measures:
  • Opioid agonist effects (measured by Visual Analog Scales and other subjective ratings) [ Time Frame: 72 hours ]
  • Physiologic effects (blood pressure, heart rate, temperature, respiratory rate, oxygen saturation, pupil diameter) [ Time Frame: 6.5 hours ]
  • Psychomotor/cognitive performance effects (measured by tasks such as the DSST and Trails B) [ Time Frame: 6.5 hours ]

Secondary Outcome Measures:
  • Pharmacokinetics (blood levels of buprenorphine and norbuprenorphine) [ Time Frame: 72 hours ]

Estimated Enrollment: 12
Study Start Date: January 2007
Estimated Study Completion Date: December 2012
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Buprenorphine
    IM, doses are blind; administered up to 1-2 times per week.
    Drug: Morphine
    IM; up to 1-2 times per week; doses double blind
    Drug: Placebo
    IM; double blind; once 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.

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

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 QTc interval
  5. current significant alcohol or sedative/hypnotic drug use
  6. 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 identifier: NCT00460239

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

Responsible Party: Eric Strain, MD, Professor, Johns Hopkins University Identifier: NCT00460239     History of Changes
Other Study ID Numbers: NIDA-08045-8  R01DA008045  DPMCDA 
Study First Received: April 11, 2007
Last Updated: April 21, 2012

Keywords provided by National Institute on Drug Abuse (NIDA):
Opioid addiction
Opioid dependence

Additional relevant MeSH terms:
Opioid-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Analgesics, Opioid
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Narcotic Antagonists processed this record on February 20, 2017