Interactions Between Intravenous Cocaine and Acetazolamide or Quinine
Information source: National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Cocaine Use; Pharmacokinetics
Intervention: cocaine (Drug); quinine (Drug); acetazolamide (Drug)
Phase: Phase 1
Status: Recruiting
Sponsored by: National Institute on Drug Abuse (NIDA) Official(s) and/or principal investigator(s): Marilyn Huestis, Ph.D., Principal Investigator, Affiliation: National Institute on Drug Abuse (NIDA)
Overall contact: Kayla N Ellefsen, Phone: (443) 740-2576, Email: ellefsenkn@mail.nih.gov
Summary
Background:
- 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.
Objectives:
- To see how they body handles acetazolamide and quinine alone, and when combined with
cocaine.
Eligibility:
- 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
Design:
- 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.
Clinical Details
Official title: Pharmacodynamic and Pharmacokinetic Interactions Between Intravenous Cocaine and Acetazolamide or Quinine
Study design: Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Diagnostic
Primary outcome: Pharmacokinetic changes for IV cocaine, acetazolamide, quinineHeart rate, blood pressure Subjective response to IV cocaine
Secondary outcome: Esterase activity in plasmaPharmacokinetic parameters for IV cocain in oral fluid Window of dectection for cocaine in oral fluid and exhaled breath
Detailed description:
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.
Eligibility
Minimum age: 18 Years.
Maximum age: 50 Years.
Gender(s): Both.
Criteria:
- INCLUSION CRITERIA
Age 18-50 years old
Smoked or used IV cocaine for at least six months and at least three times per month
during the three months prior to screening. Urine test positive for cocaine within the
prior 6 months
Adequate venous access for catheter placement
Serum sodium and potassium concentrations within normal limits (based on Johns Hopkins
Bayview Medical Center clinical laboratory)
Women with reproductive potential must use a medically acceptable form of contraception
for the duration of the study. Medically acceptable forms of contraception include: oral
contraceptive, intrauterine device (IUD), depot hormonal preparation (ring, injection
implant), or a barrier method of contraception such as a diaphragm, sponge with
spermicide, or a condom.
EXCLUSION CRITERIA
Current physical dependence on any drug other than cocaine, caffeine, or nicotine
Current clinically significant medical or psychiatric disorder, such as heart disease,
kidney disease, liver disease, adrenal insufficiency, myasthenia gravis,
glucose-6-phosphate dehydrogenase deficiency, epilepsy, stroke, optic neuritis,
hyperthyroidism, glaucoma; or psychosis, panic attacks, depression, or mania
Current sulfa allergy
Currently seeking treatment for a cocaine use disorder or in such treatment within the
prior 3 months
Current hypertension or blood pressure readings consistently above 140 mm Hg systolic or
90 mmHg diastolic while at rest
Heart rate consistently above 90 bpm or below 50 bpm while at rest
History of premature coronary artery disease or heart attack before age 50 in a first
degree biological relative
QTc greater than 450 ms or evidence of heart block, ischemia, or other clinically
significant cardiovascular disease on a 12-lead resting ECG with three-minute rhythm strip
Hemoglobin less than 12. 5 g/dL
Blood donation within 8 weeks of study entry
History of clinically significant adverse reaction to ingestion of cocaine, acetazolamide,
or quinine
Hypersensitivity to acetazolamide, sulfonamides, sulfonamide derivatives, quinine,
mefloquine or quinidine
Women who are pregnant or nursing
Currently on anti-hypertensive medication
Locations and Contacts
Kayla N Ellefsen, Phone: (443) 740-2576, Email: ellefsenkn@mail.nih.gov
National Institute on Drug Abuse, Baltimore, Maryland 21224, United States; Recruiting For more information contact Mathew's Media Group Recruiting, Phone: 800-535-8254, Email: researchstudies@mail.nih.gov
Additional Information
Related publications: Alboliras ET, Porter CJ, Ritter DG, Danielson GK, Driscoll DJ. Progressive atrioventricular block during exercise in univentricular heart. Pacing Clin Electrophysiol. 1986 Nov;9(6 Pt 1):821-5. Osterberg L, Blaschke T. Adherence to medication. N Engl J Med. 2005 Aug 4;353(5):487-97. Review. Dubbert PM, King A, Rapp SR, Brief D, Martin JE, Lake M. Riboflavin as a tracer of medication compliance. J Behav Med. 1985 Sep;8(3):287-99.
Starting date: October 2012
Last updated: January 3, 2015
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