HIV InfectionsPhase 1NCT00878306
Disulfiram Interactions With HIV Medications: Clinical Implications
A Phase 1 study testing Disulfiram, Disulfiram + Efavirenz and Disulfiram + Atazanavir in people with HIV Infections and Drug Abuse, run by University of California, San Francisco at 1 site in United States.
Trial summary
The purpose of this study is to determine whether disulfiram might be a safe and effective treatment for cocaine and/or alcohol dependence in patients with HIV disease. This research is designed to characterize the presence or absence of significant drug interactions between disulfiram and HIV medications using… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- HIV Infections, Drug Abuse
- What is being tested?
- Disulfiram, Disulfiram + Efavirenz and Disulfiram + Atazanavir
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2008to Apr 2013
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Good health and without clinical findings that require medical or psychiatric intervention as determined by a physical and mental status examination and screening laboratory tests, urinalysis, and ECG
- 18 years of age or older
- Willing to abstain from alcohol during the study and for two weeks afterward
Who cannot join
- Patients who are receiving concurrently other drugs that are inducers or inhibitors of hepatic microsomal enzymes
- Patients with a known sensitivity to the HIV therapeutics to be studied
- Pregnant or nursing mothers
- Current major affective or psychotic illnesses or suicidality
- Clinically active hepatitis
- Diabetes, hyperlipidemia, coagulation disorders, or renal disease will be excluded
- Those meeting criteria for current alcohol or drug dependence (other than nicotine)
- HIV infection
Trial locations and contacts
1 site in 1 country.
United States1 site
San Francisco General Hospital
San Francisco, California, 94110
About this study
The purpose of this study is to determine whether disulfiram might be a safe and effective treatment for cocaine and/or alcohol dependence in patients with HIV disease. This research is designed to characterize the presence or absence of significant drug interactions between disulfiram and HIV medications using standard clinical pharmacology techniques as well as monitor any side effects that might occur when these medications are administered together.
Read the detailed description
Cocaine and alcohol abuse are strongly linked to HIV infection and transmission of the virus. Disulfiram has long been approved by the US FDA for the treatment of alcohol and recent data shows it to be effective in reducing cocaine abuse. Disulfiram and antiretroviral medications (ARV) are metabolized by cytochrome P450 3A and concomitant use of these drugs could potentially produce adverse drug interactions underscoring the need to identify and understand the clinical implications of these drug interactions in order to more effectively treat individuals with both HIV disease and cocaine and/or alcohol use disorders. This will be accomplished by conducting studies aimed at identifying whether pharmacokinetic or pharmacodynamic drug interactions of importance occur between disulfiram and medications frequently utilized in those with HIV/AIDS.
Abuse of cocaine and/or alcohol has been shown to be a significant risk factor for HIV infections as a result of high risk sexual and drug use behaviors occurring in the context of use of these substances. Those with HIV infection and untreated cocaine and/or alcohol dependence are also at a high risk of transmitting HIV to others. Moreover, those with HIV disease and substance dependence often experience poor clinical outcomes as a result of nonadherence to HIV treatment regimens.
Disulfiram (DIS) is an inhibitor of ALDH and has been reported to alter hepatic cytochrome P450 enzyme function important to metabolism of many drugs frequently used in the treatment of HIV/AIDS. Although approved for the treatment of alcohol dependence, DIS has been studied as a treatment for cocaine addiction in recent years. DIS at the standard 250 mg daily dose has been associated with significant reductions in cocaine use as well as alcohol use in those with histories of concomitant cocaine-alcohol abuse. DIS 250 mg daily has been shown to have a significant pharmacokinetic interaction with cocaine resulting in delayed cocaine clearance. In order to more fully access possible use of DIS treatment for cocaine and/or alcohol dependence in this population, it is important to determine if any excess risk is conveyed as a result of drug interactions that might occur between DIS and the ARV medications.
This study will be using a standard clinical pharmacology study design using a within-subject design examining the two drug interaction studies between DIS (250 mg daily) and the following medications:
- Non-nucleoside reverse transcriptase inhibitor, efavirenz 600 mg daily for 10 days
- Protease inhibitors atazanavir 400 mg daily for 8 days or ritonavir 200 mg daily for 8 days Additional data will be collected and analyzed including:
- Clinical data on effects of these medications alone and in combination on cardiac conduction, hepatic function, and serum lipids will be obtained
- The safety of co-administration of alcohol containing HIV preparations (ritonavir) with DIS will be determined
- The effect of ARV on DIS function as determined by ALDH activity and DIS and metabolite concentrations will be determined using a control sample within-subject design (DIS doses of 62.5 mg and 250 mg daily) and between subjects design.
- Conditions
- HIV Infections, Drug Abuse
- Being tested
- Disulfiram, Disulfiram + Efavirenz, Disulfiram + Atazanavir, Disulfiram + Ritonavir
- Keywords
- Treatment of drug dependency with HIV medications, HIV
- Medical subject headings
- HIV Infections, Substance-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DisulfiramDrug
Also called Antabuse
62.5 mg daily x3 days, then 250 mg daily x3 days
Disulfiram + EfavirenzDrug
Efavirenz 600 mg daily x10 days, then in addition with 62.5 mg daily x3 days, then Disulfiram 250 mg daily x3 days
Disulfiram + AtazanavirDrug
Atazanavir 400 mg daily x8 days, then in addition with 62.5 mg daily x3 days, then Disulfiram 250 mg daily x3 days
Disulfiram + RitonavirDrug
Ritonavir 200 mg daily x8 days, then in addition with 62.5 mg daily x3 days, then Disulfiram 250 mg daily x3 days
| Study group | Role | What they receive |
|---|---|---|
| Disulfiram | Active comparator | Disulfiram Receives: Drug: Disulfiram |
| Disulfiram + Efavirenz | Experimental | Efavirenz alone, then in addition with Disulfiram Receives: Drug: Disulfiram + Efavirenz |
| Disulfiram + Atazanavir | Experimental | Atazanavir alone, then in addition with Disulfiram Receives: Drug: Disulfiram + Atazanavir |
| Disulfiram + Ritonavir | Experimental | Ritonavir alone, then in addition with Disulfiram Receives: Drug: Disulfiram + Ritonavir |
What is being measured
The primary outcome is the main question the study is designed to answer.
The effect of disulfiram on the pharmacokinetics of each of the antiretroviral medications to be studied
Measured: Measured at Day 15
Secondary outcomes (5)
The effect of the antiretroviral medications on disulfiram measured by ALDH activity and disulfiram pharmacokinetics
Measured: Measured at Day 0, Day 4, and Day 8
Cardiac Conduction
Measured: Measured at screening and during pharmacokinetic studies
Hepatic Function
Measured: Measured at screening and during pharmacokinetic studies
Serum Lipids
Measured: Measured at screening and during pharmacokinetic studies
Safety of co-administration of alcohol containing HIV preparations (ritonavir) and Disulfiram
Measured: Measured at day 11- day 15
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2009 (estimated)
- Study startNov 2008
- Primary completionApr 2013
- Study completionApr 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- 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
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Sponsor
- Investigators
- Elinore F McCance-Katz, M.D., Ph.D, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00878306
- Sponsor's protocol ID
- R01DA024982
- Other IDs
- R01DA024982
- Status last verified
- May 2014
- First submitted
- 7 Apr 2009
- Last updated
- 6 May 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Disulfiram Interactions With HIV Medications: Clinical Implications
- ClinicalTrials.gov ID
- NCT00878306
- Acronym / sponsor ID
- R01DA024982
- Conditions
- HIV Infections, Drug Abuse
- Keywords
- Treatment of drug dependency with HIV medications, HIV
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- Nov 2008
- Primary completion
- Apr 2013 (actual)
- Study completion
- Apr 2013 (actual)
- First posted
- 8 Apr 2009 (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.
The purpose of this study is to determine whether disulfiram might be a safe and effective treatment for cocaine and/or alcohol dependence in patients with HIV disease. This research is designed to characterize the presence or absence of significant drug interactions between disulfiram and HIV medications using standard clinical pharmacology techniques as well as monitor any side effects that might occur when these medications are administered together.
Detailed description
Cocaine and alcohol abuse are strongly linked to HIV infection and transmission of the virus. Disulfiram has long been approved by the US FDA for the treatment of alcohol and recent data shows it to be effective in reducing cocaine abuse. Disulfiram and antiretroviral medications (ARV) are metabolized by cytochrome P450 3A and concomitant use of these drugs could potentially produce adverse drug interactions underscoring the need to identify and understand the clinical implications of these drug interactions in order to more effectively treat individuals with both HIV disease and cocaine and/or alcohol use disorders. This will be accomplished by conducting studies aimed at identifying whether pharmacokinetic or pharmacodynamic drug interactions of importance occur between disulfiram and medications frequently utilized in those with HIV/AIDS.
Abuse of cocaine and/or alcohol has been shown to be a significant risk factor for HIV infections as a result of high risk sexual and drug use behaviors occurring in the context of use of these substances. Those with HIV infection and untreated cocaine and/or alcohol dependence are also at a high risk of transmitting HIV to others. Moreover, those with HIV disease and substance dependence often experience poor clinical outcomes as a result of nonadherence to HIV treatment regimens.
Disulfiram (DIS) is an inhibitor of ALDH and has been reported to alter hepatic cytochrome P450 enzyme function important to metabolism of many drugs frequently used in the treatment of HIV/AIDS. Although approved for the treatment of alcohol dependence, DIS has been studied as a treatment for cocaine addiction in recent years. DIS at the standard 250 mg daily dose has been associated with significant reductions in cocaine use as well as alcohol use in those with histories of concomitant cocaine-alcohol abuse. DIS 250 mg daily has been shown to have a significant pharmacokinetic interaction with cocaine resulting in delayed cocaine clearance. In order to more fully access possible use of DIS treatment for cocaine and/or alcohol dependence in this population, it is important to determine if any excess risk is conveyed as a result of drug interactions that might occur between DIS and the ARV medications.
This study will be using a standard clinical pharmacology study design using a within-subject design examining the two drug interaction studies between DIS (250 mg daily) and the following medications:
- Non-nucleoside reverse transcriptase inhibitor, efavirenz 600 mg daily for 10 days
- Protease inhibitors atazanavir 400 mg daily for 8 days or ritonavir 200 mg daily for 8 days Additional data will be collected and analyzed including:
- Clinical data on effects of these medications alone and in combination on cardiac conduction, hepatic function, and serum lipids will be obtained
- The safety of co-administration of alcohol containing HIV preparations (ritonavir) with DIS will be determined
- The effect of ARV on DIS function as determined by ALDH activity and DIS and metabolite concentrations will be determined using a control sample within-subject design (DIS doses of 62.5 mg and 250 mg daily) and between subjects design.
Study design
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Disulfiram | Active comparator | Drug: DisulfiramDisulfiram |
| Disulfiram + Efavirenz | Experimental | Drug: Disulfiram + EfavirenzEfavirenz alone, then in addition with Disulfiram |
| Disulfiram + Atazanavir | Experimental | Drug: Disulfiram + AtazanavirAtazanavir alone, then in addition with Disulfiram |
| Disulfiram + Ritonavir | Experimental | Drug: Disulfiram + RitonavirRitonavir alone, then in addition with Disulfiram |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Good health and without clinical findings that require medical or psychiatric intervention as determined by a physical and mental status examination and screening laboratory tests, urinalysis, and ECG
- 18 years of age or older
- Willing to abstain from alcohol during the study and for two weeks afterward
Key exclusion criteria (8 listed)
- Patients who are receiving concurrently other drugs that are inducers or inhibitors of hepatic microsomal enzymes
- Patients with a known sensitivity to the HIV therapeutics to be studied
- Pregnant or nursing mothers
- Current major affective or psychotic illnesses or suicidality
- Clinically active hepatitis
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 |
|---|---|---|
| DisulfiramAlso: Antabuse62.5 mg daily x3 days, then 250 mg daily x3 days | Drug | Disulfiram |
| Disulfiram + EfavirenzEfavirenz 600 mg daily x10 days, then in addition with 62.5 mg daily x3 days, then Disulfiram 250 mg daily x3 days | Drug | Disulfiram + Efavirenz |
| Disulfiram + AtazanavirAtazanavir 400 mg daily x8 days, then in addition with 62.5 mg daily x3 days, then Disulfiram 250 mg daily x3 days | Drug | Disulfiram + Atazanavir |
| Disulfiram + RitonavirRitonavir 200 mg daily x8 days, then in addition with 62.5 mg daily x3 days, then Disulfiram 250 mg daily x3 days | Drug | Disulfiram + Ritonavir |
Primary outcome
The effect of disulfiram on the pharmacokinetics of each of the antiretroviral medications to be studied
Time frame: Measured at Day 15
5 secondary outcomes
The effect of the antiretroviral medications on disulfiram measured by ALDH activity and disulfiram pharmacokinetics
Time frame: Measured at Day 0, Day 4, and Day 8
Cardiac Conduction
Time frame: Measured at screening and during pharmacokinetic studies
Hepatic Function
Time frame: Measured at screening and during pharmacokinetic studies
Serum Lipids
Time frame: Measured at screening and during pharmacokinetic studies
Safety of co-administration of alcohol containing HIV preparations (ritonavir) and Disulfiram
Time frame: Measured at day 11- day 15
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 6 May 2014.
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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.
Elinore F McCance-Katz, M.D., Ph.D principal investigator
University of California, San Francisco
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 Disulfiram, Disulfiram + Efavirenz and Disulfiram + Atazanavir in people with HIV Infections and Drug Abuse, run by University of California, San Francisco 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 3 inclusion and 8 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 6 May 2014. 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?
The effect of disulfiram on the pharmacokinetics of each of the antiretroviral medications to be studied (time frame: Measured at Day 15). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 6 May 2014.