Cocaine UsePhase 1NCT01851473
Interactions Between Intravenous Cocaine and Acetazolamide or Quinine
A Phase 1 study testing cocaine, quinine and acetazolamide in people with Cocaine Use and Pharmacokinetics, run by National Institute on Drug Abuse (NIDA) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Cocaine Use, Pharmacokinetics
- What is being tested?
- cocaine, quinine and acetazolamide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Oct 2012to 7 Oct 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 14Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute on Drug Abuse
Baltimore, Maryland, 21224
About this study
Official title: Pharmacodynamic and Pharmacokinetic Interactions Between Intravenous Cocaine and Acetazolamide or Quinine
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.
Read more
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.
Read the 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.
- Conditions
- Cocaine Use, Pharmacokinetics
- Being tested
- cocaine, quinine, acetazolamide
- Keywords
- Cocaine, Pharmacokinetics, Pharmacodynamics, Drug Interactions, Acetazolamide
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cocaineDrug
25 mg IV on days 1, 5, and 10
quinineDrug
80 mg orally on days 7-10
acetazolamideDrug
15 mg orally on days 2-5
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetic changes for IV cocaine, acetazolamide, quinine
Measured: 24 hours
Heart rate, blood pressure
Measured: 3 hours
Subjective response to IV cocaine
Measured: 3 hours
Secondary outcomes (3)
Esterase activity in plasma
Measured: 4 days
Pharmacokinetic parameters for IV cocain in oral fluid
Measured: 24 hours
Window of dectection for cocaine in oral fluid and exhaled breath
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2013 (estimated)
- Study start24 Oct 2012
- Primary completion7 Oct 2015
- Study completion7 Oct 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Cocaine UseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute on Drug Abuse (NIDA)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Marilyn Huestis, Ph.D., Principal investigator, National Institute on Drug Abuse (NIDA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01851473
- Sponsor's protocol ID
- 999913482
- Other IDs
- 13-DA-N482
- Status last verified
- 7 Oct 2015
- First submitted
- 9 May 2013
- Last updated
- 5 Jul 2018
- Results posted
- No
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):821-5. doi: 10.1111/j.1540-8159.1986.tb06631.x.
PubMed 2432484Osterberg L, Blaschke T. Adherence to medication. N Engl J Med. 2005 Aug 4;353(5):487-97. doi: 10.1056/NEJMra050100. No abstract available.
PubMed 16079372Dubbert 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.
PubMed 4087291Bouhlal 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.
PubMed 28881319
Study at a glance
From the registry record, last updated by the sponsor on 5 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacodynamic and Pharmacokinetic Interactions Between Intravenous Cocaine and Acetazolamide or Quinine
- ClinicalTrials.gov ID
- NCT01851473
- Acronym / sponsor ID
- 999913482
- Conditions
- Cocaine Use, Pharmacokinetics
- Keywords
- Cocaine, Pharmacokinetics, Pharmacodynamics, Drug Interactions, Acetazolamide
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- National Institute on Drug Abuse (NIDA)US National Institutes of Health
- Study start
- 24 Oct 2012
- Primary completion
- 7 Oct 2015 (actual)
- Study completion
- 7 Oct 2015 (actual)
- First posted
- 10 May 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| cocaine25 mg IV on days 1, 5, and 10 | Drug | – |
| quinine80 mg orally on days 7-10 | Drug | – |
| acetazolamide15 mg orally on days 2-5 | Drug | – |
Primary outcome
Pharmacokinetic changes for IV cocaine, acetazolamide, quinine
Time frame: 24 hours
Heart rate, blood pressure
Time frame: 3 hours
Subjective response to IV cocaine
Time frame: 3 hours
3 secondary outcomes
Esterase activity in plasma
Time frame: 4 days
Pharmacokinetic parameters for IV cocain in oral fluid
Time frame: 24 hours
Window of dectection for cocaine in oral fluid and exhaled breath
Time frame: 24 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jul 2018.
- Background: PubMed 2432484Alboliras 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.
- Background: PubMed 16079372Osterberg L, Blaschke T. Adherence to medication. N Engl J Med. 2005 Aug 4;353(5):487-97. doi: 10.1056/NEJMra050100. No abstract available.
- Background: PubMed 4087291Dubbert 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.
- Derived from this study: PubMed 28881319Bouhlal 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marilyn Huestis, Ph.D. principal investigator
National Institute on Drug Abuse (NIDA)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing cocaine, quinine and acetazolamide in people with Cocaine Use and Pharmacokinetics, run by National Institute on Drug Abuse (NIDA) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pharmacokinetic changes for IV cocaine, acetazolamide, quinine (time frame: 24 hours). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01851473, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jul 2018.