Interactions Between Intravenous Cocaine and Acetazolamide or Quinine

NCT01851473 | Completed Phase 1

• 2 other identifiers: 99991348213-DA-N482
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Cocaine Use; Pharmacokinetics

Keywords

Cocaine; Pharmacokinetics; Pharmacodynamics; Drug Interactions; Acetazolamide

Outcome Measures

Primary Outcomes (3)

• Pharmacokinetic changes for IV cocaine, acetazolamide, quinine

  24 hours

• Heart rate, blood pressure

  3 hours

• Subjective response to IV cocaine

  3 hours

Secondary Outcomes (3)

• Esterase activity in plasma

  4 days

• Pharmacokinetic parameters for IV cocain in oral fluid

  24 hours

• Window of dectection for cocaine in oral fluid and exhaled breath

  24 hours

Interventions

cocaine DRUG

25 mg IV on days 1, 5, and 10

quinine DRUG

80 mg orally on days 7-10

acetazolamide DRUG

15 mg orally on days 2-5

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute on Drug Abuse (NIDA): lead

Study Sites (1)

National Institute on Drug Abuse

Baltimore, Maryland, 21224, United States

Location

Related Publications (4)

• 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):821-5. doi: 10.1111/j.1540-8159.1986.tb06631.x.

  PMID: 2432484 BACKGROUND

• Osterberg L, Blaschke T. Adherence to medication. N Engl J Med. 2005 Aug 4;353(5):487-97. doi: 10.1056/NEJMra050100. No abstract available.

  PMID: 16079372 BACKGROUND

• 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. doi: 10.1007/BF00870315.

  PMID: 4087291 BACKGROUND

• Bouhlal S, Ellefsen KN, Sheskier MB, Singley E, Pirard S, Gorelick DA, Huestis MA, Leggio L. Acute effects of intravenous cocaine administration on serum concentrations of ghrelin, amylin, glucagon-like peptide-1, insulin, leptin and peptide YY and relationships with cardiorespiratory and subjective responses. Drug Alcohol Depend. 2017 Nov 1;180:68-75. doi: 10.1016/j.drugalcdep.2017.07.033. Epub 2017 Aug 31.

  PMID: 28881319 DERIVED

MeSH Terms

Interventions

Cocaine; Quinine; Acetazolamide

Intervention Hierarchy (Ancestors)

Tropanes; Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring; Cinchona Alkaloids; Quinuclidines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Thiadiazoles; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring

Study Officials

• Marilyn Huestis, Ph.D.

  National Institute on Drug Abuse (NIDA)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 9, 2013
• First Posted: May 10, 2013
• Study Start: October 24, 2012
• Primary Completion: October 7, 2015
• Study Completion: October 7, 2015
• Last Updated: July 5, 2018

Record last verified: 2015-10-07

Locations

US (1)