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NCT Number: NCT00460239

Buprenorphine's Dose Response Curve

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).

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Key information

Conditions

Opioid-related Disorders Chemically-Induced Disorders Mental Disorders Narcotic-Related Disorders Substance-Related Disorders

Age range

21 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Johns Hopkins University (BPRU) Bayview Campus

Baltimore, Maryland, 21224, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • current opioid abuse but not physically dependent on opioids

Exclusion criteria

  • 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

Treatment and study plan

buprenorphine

Drug

Intramuscular, doses (8, 16, 32, 48, 60 mg) are blind; administered up to 1-2 times per week.

Morphine

Drug

Intramuscular; up to 1-2 times per week; doses (15, 30 mg) double blind

Placebo

Drug

Intramuscular; double blind; once per week

Primary outcomes

  1. 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.

  2. 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.

  3. 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.

  4. Physiologic Effects as Assessed by Blood Pressure

    Time frame: Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)

  5. Physiologic Effects as Assessed by Heart Rate

    Time frame: Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)

  6. Physiologic Effects as Assessed by Body Temperature

    Time frame: Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)

  7. Physiologic Effects as Assessed by Oxygen Saturation

    Time frame: Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)

  8. Physiologic Effects as Assessed by Pupil Diameter

    Time frame: Each experimental test session (8 experimental test sessions assessed for up to 6-7 weeks)

Sponsors and collaborators

Lead sponsor

Johns Hopkins University

Other

Collaborators

  • National Institute on Drug Abuse (NIDA)

Registry information

Official study title

Evaluation of Opioid Antagonist Activity in Humans

Important dates

Study start
2007
Primary completion
2009
Study completion
2009
First posted
Apr 13, 2007
Registry last updated
Mar 3, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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