Interactions Between Intravenous Cocaine and Acetazolamide or Quinine
- Scientists are studying medications that may be useful in treating cocaine addiction. It is important in these studies to know whether study participants are always taking their medications as directed. This study will look at two chemicals to see if they can be used to determine whether participants are taking their medications as directed. Because acetazolamide and quinine can be measured in plasma and urine, they are good test subjects for this study. They will be given alone, and combined with intravenous cocaine.
- To see how they body handles acetazolamide and quinine alone, and when combined with cocaine.
- Individuals between 18 and 50 years of age who have smoked or used IV cocaine for at least one year and at least three times per month during the three months prior to screening. Urine test positive for cocaine within the prior 6 months
- Participants will be screened with a physical exam and medical history. Blood and urine samples will also be collected.
- This study will involve a 12-day inpatient stay at the National Institutes of Health.
- On days 1, 5, and 10, participants will receive a dose of cocaine. Blood, urine, breath, and saliva samples will be collected up to 18 times a day for up to about 24 hours.
- On days 2, 3, 4, and 5, participants will receive acetazolamide. Regular blood samples will be collected on Day 4.
- Day 6 is a wash-out day with no drugs or blood tests.
- On days 7, 8, 9, and 10, participants will receive quinine. Regular blood samples will be collected on Day 9.
- On day 11, blood, urine, breath, and saliva samples will be collected in the early morning. Participants will be able to leave later in the day.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Diagnostic
|Official Title:||Pharmacodynamic and Pharmacokinetic Interactions Between Intravenous Cocaine and Acetazolamide or Quinine|
- Pharmacokinetic changes for IV cocaine, acetazolamide, quinine [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
- Heart rate, blood pressure [ Time Frame: 3 hours ] [ Designated as safety issue: Yes ]
- Subjective response to IV cocaine [ Time Frame: 3 hours ] [ Designated as safety issue: No ]
- Esterase activity in plasma [ Time Frame: 4 days ] [ Designated as safety issue: No ]
- Pharmacokinetic parameters for IV cocain in oral fluid [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
- Window of dectection for cocaine in oral fluid and exhaled breath [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
|Study Start Date:||October 2012|
|Estimated Study Completion Date:||December 2015|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
Background: Cocaine dependence is a public health concern worldwide, with no FDA-approved pharmacological treatment for this condition. Thus, there is a need for controlled clinical trials to evaluate potential new pharmacological treatments. Adherence to a medication regime is a major factor in the success of treatment. In controlled clinical trials, medication adherence is often monitored by measuring specific markers ingested with the medication. No such markers are validated for use in studies of cocaine dependence treatment.
Objective: Evaluate the feasibility of oral acetazolamide and quinine as adherence markers in trials of cocaine dependence treatment by determining their pharmacodynamic and pharmacokinetic interactions with intravenous (IV) cocaine.
Study Population: Up to 30 healthy cocaine users aged 18-50 years who smoked or used IV cocaine for at least one year and at least three times per month during the three months prior to screening and had a positive urine test for cocaine within the last 6 months.
Experimental Design and Methods: Participants are admitted to a secure residential research unit on and undergo baseline assessments on Day -1, receive training on Day 0, and receive single doses of IV cocaine (25 mg) on Days 1, 5 and 10. On Days 1, 5, and 10, dried blood spot specimens are collected up to 3 times daily over 1.5 h. Single oral doses of acetazolamide (15 mg) are given on Days 2-5 and quinine (80 mg) on Days 7-10. Blood, oral fluid, and breath specimens are collected for up to 71 h, 70 h, and 22 h, respectively, after drug administration on Days 1, 4, 5, 9 and 10. Participants will wear the AutoSense device on Days 1, 3, 4, 5, 8, 9 and 10 for up to 12 hours each day. All voided urine is collected throughout the study.
Outcome measures: Primary outcome measures include cocaine, benzoylecgonine, ecgonine methylester, norcocaine, acetazolamide, and quinine pharmacokinetics in plasma and urine and whether subjective and cardiovascular responses to IV cocaine are changed when coadministered with oral acetazolamide or quinine. Secondary outcome measures include cocaine pharmacokinetics in oral fluid and breath, plasma activity of BChE and carboxylesterase (enzymes which metabolize cocaine), and basal and post-cocaine administration serum concentrations of leptin and other appetitive peptides (e.g. ghrelin, GLP-1, insulin, PYY, amylin).
Benefits: There is no direct benefit to participants, but the study is likely to yield generalizable knowledge about the feasibility of acetazolamide and quinine as markers of medication adherence in future studies of pharmacological treatment for cocaine dependence.
Risks: < TAB> This study poses greater than minimal risk for participants because of IV cocaine administration.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01851473
|Contact: Kayla N Ellefsen||(443) email@example.com|
|Contact: Marilyn Huestis, Ph.D.||(410) firstname.lastname@example.org|
|United States, Maryland|
|National Institute on Drug Abuse||Recruiting|
|Baltimore, Maryland, United States, 21224|
|Contact: For more information contact Mathew's Media Group Recruiting 800-535-8254 email@example.com|
|Principal Investigator:||Marilyn Huestis, Ph.D.||National Institute on Drug Abuse (NIDA)|