Methamphetamine DependencePhase 2RAVENNCT01011829
Varenicline vs Placebo for the Treatment of Methamphetamine Dependence
A Phase 2 study testing Varenicline in people with Methamphetamine Dependence and Substance Abuse, run by University of California, Los Angeles at 1 site in United States.
Trial summary
Methamphetamine (MA) abuse is the fastest growing drug problem in the United States and is responsible for significant public health complications, including HIV infection. As a result effective treatments for MA dependence are urgently needed. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Methamphetamine Dependence, Substance Abuse, Methamphetamine Abuse
- What is being tested?
- Varenicline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2009to May 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18 years of age or older;
- meet (Diagnostic and Statistical Manual of Mental Disorders) DSM-IV criteria for methamphetamine (MA) dependence;
- seeking treatment for MA problems;
- willing and able to comply with study procedures;
- willing and able to provide written informed consent;
- if female, not pregnant or lactating and willing to use an acceptable method of barrier birth control (e.g. condoms) during the trial.
Who cannot join
- have a medical condition that, in the study physician's judgment, may interfere with safe study participation (e.g., active tuberculosis, unstable cardiac, renal, or liver disease, uncontrolled hypertension, unstable diabetes);
- have a current neurological disorder (e.g., organic brain disease, dementia) or a medical history which would make study agent compliance difficult or which would compromise informed consent;
- have a current major psychiatric disorder not due to substance abuse (e.g., schizophrenia, bipolar disorder) as assessed by the Structured Clinical Interview for DSM Disorders (SCID);
- have a history of attempted suicide in the past 3 years and/or serious suicidal intention or plan in the past year as assessed by the Columbia Suicide Severity Rating Scale (C-SSRS);
- currently on prescription medication that is contraindicated for use with varenicline;
- currently using any form of nicotine replacement therapy, due to potential interactions with varenicline;
Show all 9Show fewer
- have current dependence on cocaine, opiates, alcohol, or benzodiazepines as defined by DSM-IV;
- have a history of alcohol dependence within the past three years;
- have a history of sensitivity to varenicline or any other circumstances that, in the opinion of the investigators, would compromise participant safety.
Trial locations and contacts
1 site in 1 country.
United States1 site
UCLA Vine Street Clinic
Los Angeles, California, 90038
About this study
Official title: A Randomized, Double-blind Trial of Varenicline Versus Placebo, in Conjunction With Cognitive Behavioral Therapy, for Methamphetamine Dependence
Methamphetamine (MA) abuse is the fastest growing drug problem in the United States and is responsible for significant public health complications, including HIV infection. As a result effective treatments for MA dependence are urgently needed. There are currently no efficacious medications for MA dependence, although results from preliminary randomized trials of bupropion for MA dependence found bupropion to be more effective than placebo, but only among subgroups of participants, including those with lower frequency of MA use at baseline. A growing body of preclinical and clinical studies suggest that cholinergic mechanisms play an important role in the neurobiology of MA and other stimulant dependence, such as nicotine dependence. Mechanistically, cholinergic medications may alleviate MA-associated cognitive dysfunction, thereby improving outcomes of treatment for MA dependence. Varenicline is a partial agonist at α4β2 nicotinic receptors and a full agonist at α7 nicotinic receptors that has been approved as an anti-cigarette smoking medication. In order to assess the potential efficacy of varenicline for methamphetamine dependence, we will perform a clinical trial to assess if varenicline compared to placebo results in greater:
- reductions in methamphetamine use;
- treatment retention;
Read the detailed description
Methamphetamine (MA) abuse is the fastest growing drug problem in the United States and is responsible for significant public health complications, including HIV infection1. As a result effective treatments for MA dependence are urgently needed. There are currently no efficacious medications for MA dependence, although results from preliminary randomized trials of bupropion for MA dependence found bupropion to be more effective than placebo, but only among subgroups of participants, including those with lower frequency of MA use at baseline 2, 3. A growing body of preclinical and clinical studies suggest that cholinergic mechanisms play an important role in the neurobiology of MA and other stimulant dependence, such as nicotine dependence 4. Mechanistically, cholinergic medications may alleviate MA-associated cognitive dysfunction, thereby improving outcomes of treatment for MA dependence 5. Varenicline is a partial agonist at α4β2 nicotinic receptors and a full agonist at α7 nicotinic receptors that has been approved as an anti-cigarette smoking medication. In order to assess the potential efficacy of varenicline for methamphetamine dependence, we will perform a clinical trial to assess the following aims:
- To determine if varenicline results in significantly greater reductions in methamphetamine use than placebo, as determined via the proportion of methamphetamine-free urine specimens provided by participants throughout treatment, when provided to methamphetamine dependent participants in conjunction with cognitive behavioral therapy. Exploratory Aim 1a. To determine whether reductions in methamphetamine use with varenicline versus placebo are greater among methamphetamine dependent participants with baseline light MA use (MA use on 18 or fewer of the past 30 days at baseline) versus heavy MA use (MA use on more than 18 of the past 30 days). Exploratory Aim 1b. To determine if varenicline results in a greater proportion of methamphetamine dependent participants achieving methamphetamine abstinence defined as self-reported MA abstinence, confirmed via urine drug screens (all available urine drug screens are MA-metabolite free and at least one urine drug screen available per week and no more than two missed visits between urine drug screens) during the final two weeks of the study medication period (weeks 7 and 8) relative to placebo when provided in conjunction with cognitive behavioral therapy.
- To determine if varenicline results in significantly greater treatment retention than placebo among MA dependent participants when provided in conjunction with cognitive behavioral therapy.
To address these aims, we recruited 20 MA dependent participants who will be randomized to receive treatment with varenicline (n=10) or placebo (n=10) for 8 weeks, in combination with cognitive behavioral therapy, followed by 4 weeks of follow up observation.
Results of this study have the potential to provide additional safety data and to yield preliminary evidence that may support a fully powered late Phase II trial of the efficacy of varenicline for the treatment of methamphetamine dependence. Findings also have potential to provide insights into the influence of cognitive dysfunction, and medications with potential cognitive enhancing effects, on the pathogenesis of MA dependence and treatment outcomes.
- Being tested
- Varenicline, Placebo
- Keywords
- methamphetamine, crystal meth, addiction, los angeles, medication, meth
- Medical subject headings
- Substance-Related Disorders, Behavior, Addictive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VareniclineDrug
Also called CHANTIX (tm)
Varenicline dosing will follow that which has been shown to be effective for cigarette smoking cessation. Varenicline dose will start at 0.5 mg daily for days 1-3, followed by 0.5 mg twice daily for days 4-7, followed by 1 mg twice daily from day 8 until completion of the medication period (end of week 8).
PlaceboDrug
Also called Sugar pill
Placebo dose will start at 0.5 mg (sugar pill) daily for days 1-3, followed by 0.5 mg twice daily for days 4-7, followed by 1 mg twice daily from day 8 until completion of the medication period (end of week 8).
| Study group | Role | What they receive |
|---|---|---|
| Varenicline | Active comparator | Varenicline:
0.5 mg daily for days 1-3
0.5 mg twice daily for days 4-7
1 mg twice daily from day 8 until end of week 8. Receives: Drug: Varenicline |
| Placebo | Placebo comparator | 8 weeks of daily matching oral placebo in tablet form Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in MA Positive Urine Drug Screens Among Participants Randomly Assigned to Receive Varenicline Versus Placebo.
Urine samples, collected thrice weekly, were tested for metabolites of MA using radioimmunoassay. Each subject had a possible of 24 urine drug screens to provide during the 8 weeks of medication. An aggregate measure of urine drug screen results was calculated - the Treatment Effectiveness Score (TES) - which is the average of the sum of MA-free urine specimens provided during the treatment period by participants in each treatment condition.
Measured: 8-weeks
Secondary outcomes (1)
Retention (Completion)
Retention was determined by the proportion of participants retained for the entire trial and time until drop-out.
Measured: 8-weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Nov 2009 (estimated)
- Study startNov 2009
- Primary completionMay 2010
- Study completionMay 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Methamphetamine DependenceStudies of the same condition, open and under way.
- More trials run by University of California, Los AngelesThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Los Angeles
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Principal investigator, Steve Shoptaw, University of California, Los Angeles
- Investigators
- Steven Shoptaw, PhD, Principal investigator, UCLA Dept of Family Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01011829
- Sponsor's protocol ID
- NIDA-18185-PII-3
- Other IDs
- P50DA018185, DPMC
- Acronym
- RAVEN
- Status last verified
- Feb 2013
- First submitted
- 9 Nov 2009
- Last updated
- 14 Mar 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 14 Mar 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind Trial of Varenicline Versus Placebo, in Conjunction With Cognitive Behavioral Therapy, for Methamphetamine Dependence
- ClinicalTrials.gov ID
- NCT01011829
- Acronym / sponsor ID
- RAVEN / NIDA-18185-PII-3
- Keywords
- methamphetamine, crystal meth, addiction, los angeles, medication, meth
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University of California, Los AngelesUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- Nov 2009
- Primary completion
- May 2010 (actual)
- Study completion
- May 2010 (actual)
- First posted
- 11 Nov 2009 (estimated)
- Results
- Posted 14 Mar 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Methamphetamine (MA) abuse is the fastest growing drug problem in the United States and is responsible for significant public health complications, including HIV infection. As a result effective treatments for MA dependence are urgently needed. There are currently no efficacious medications for MA dependence, although results from preliminary randomized trials of bupropion for MA dependence found bupropion to be more effective than placebo, but only among subgroups of participants, including those with lower frequency of MA use at baseline. A growing body of preclinical and clinical studies suggest that cholinergic mechanisms play an important role in the neurobiology of MA and other stimulant dependence, such as nicotine dependence. Mechanistically, cholinergic medications may alleviate MA-associated cognitive dysfunction, thereby improving outcomes of treatment for MA dependence. Varenicline is a partial agonist at α4β2 nicotinic receptors and a full agonist at α7 nicotinic receptors that has been approved as an anti-cigarette smoking medication. In order to assess the potential efficacy of varenicline for methamphetamine dependence, we will perform a clinical trial to assess if varenicline compared to placebo results in greater:
- reductions in methamphetamine use;
- treatment retention;
Detailed description
Methamphetamine (MA) abuse is the fastest growing drug problem in the United States and is responsible for significant public health complications, including HIV infection1. As a result effective treatments for MA dependence are urgently needed. There are currently no efficacious medications for MA dependence, although results from preliminary randomized trials of bupropion for MA dependence found bupropion to be more effective than placebo, but only among subgroups of participants, including those with lower frequency of MA use at baseline 2, 3. A growing body of preclinical and clinical studies suggest that cholinergic mechanisms play an important role in the neurobiology of MA and other stimulant dependence, such as nicotine dependence 4. Mechanistically, cholinergic medications may alleviate MA-associated cognitive dysfunction, thereby improving outcomes of treatment for MA dependence 5. Varenicline is a partial agonist at α4β2 nicotinic receptors and a full agonist at α7 nicotinic receptors that has been approved as an anti-cigarette smoking medication. In order to assess the potential efficacy of varenicline for methamphetamine dependence, we will perform a clinical trial to assess the following aims:
- To determine if varenicline results in significantly greater reductions in methamphetamine use than placebo, as determined via the proportion of methamphetamine-free urine specimens provided by participants throughout treatment, when provided to methamphetamine dependent participants in conjunction with cognitive behavioral therapy. Exploratory Aim 1a. To determine whether reductions in methamphetamine use with varenicline versus placebo are greater among methamphetamine dependent participants with baseline light MA use (MA use on 18 or fewer of the past 30 days at baseline) versus heavy MA use (MA use on more than 18 of the past 30 days). Exploratory Aim 1b. To determine if varenicline results in a greater proportion of methamphetamine dependent participants achieving methamphetamine abstinence defined as self-reported MA abstinence, confirmed via urine drug screens (all available urine drug screens are MA-metabolite free and at least one urine drug screen available per week and no more than two missed visits between urine drug screens) during the final two weeks of the study medication period (weeks 7 and 8) relative to placebo when provided in conjunction with cognitive behavioral therapy.
- To determine if varenicline results in significantly greater treatment retention than placebo among MA dependent participants when provided in conjunction with cognitive behavioral therapy.
To address these aims, we recruited 20 MA dependent participants who will be randomized to receive treatment with varenicline (n=10) or placebo (n=10) for 8 weeks, in combination with cognitive behavioral therapy, followed by 4 weeks of follow up observation.
Results of this study have the potential to provide additional safety data and to yield preliminary evidence that may support a fully powered late Phase II trial of the efficacy of varenicline for the treatment of methamphetamine dependence. Findings also have potential to provide insights into the influence of cognitive dysfunction, and medications with potential cognitive enhancing effects, on the pathogenesis of MA dependence and treatment outcomes.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Varenicline | Active comparator | Drug: VareniclineVarenicline: 0.5 mg daily for days 1-3 0.5 mg twice daily for days 4-7 1 mg twice daily from day 8 until end of week 8. |
| Placebo | Placebo comparator | Drug: Placebo8 weeks of daily matching oral placebo in tablet form |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 18 years of age or older;
- meet (Diagnostic and Statistical Manual of Mental Disorders) DSM-IV criteria for methamphetamine (MA) dependence;
- seeking treatment for MA problems;
- willing and able to comply with study procedures;
- willing and able to provide written informed consent;
Key exclusion criteria (9 listed)
- have a medical condition that, in the study physician's judgment, may interfere with safe study participation (e.g., active tuberculosis, unstable cardiac, renal, or liver disease, uncontrolled hypertension, unstable diabetes);
- have a current neurological disorder (e.g., organic brain disease, dementia) or a medical history which would make study agent compliance difficult or which would compromise informed consent;
- have a current major psychiatric disorder not due to substance abuse (e.g., schizophrenia, bipolar disorder) as assessed by the Structured Clinical Interview for DSM Disorders (SCID);
- have a history of attempted suicide in the past 3 years and/or serious suicidal intention or plan in the past year as assessed by the Columbia Suicide Severity Rating Scale (C-SSRS);
- currently on prescription medication that is contraindicated for use with varenicline;
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 |
|---|---|---|
| VareniclineAlso: CHANTIX (tm)Varenicline dosing will follow that which has been shown to be effective for cigarette smoking cessation. Varenicline dose will start at 0.5 mg daily for days 1-3, followed by 0.5 mg twice daily for days 4-7, followed by 1 mg twice daily from day 8 until completion of the medication period (end of week 8). | Drug | Varenicline |
| PlaceboAlso: Sugar pillPlacebo dose will start at 0.5 mg (sugar pill) daily for days 1-3, followed by 0.5 mg twice daily for days 4-7, followed by 1 mg twice daily from day 8 until completion of the medication period (end of week 8). | Drug | Placebo |
Primary outcome
Change in MA Positive Urine Drug Screens Among Participants Randomly Assigned to Receive Varenicline Versus Placebo.
Time frame: 8-weeks
Urine samples, collected thrice weekly, were tested for metabolites of MA using radioimmunoassay. Each subject had a possible of 24 urine drug screens to provide during the 8 weeks of medication. An aggregate measure of urine drug screen results was calculated - the Treatment Effectiveness Score (TES) - which is the average of the sum of MA-free urine specimens provided during the treatment period by participants in each treatment condition.
1 secondary outcome
Retention (Completion)
Time frame: 8-weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Mar 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Steven Shoptaw, PhD principal investigator
UCLA Dept of Family Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Varenicline in people with Methamphetamine Dependence and Substance Abuse, run by University of California, Los Angeles 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 6 inclusion and 9 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 14 Mar 2013. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Mar 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in MA Positive Urine Drug Screens Among Participants Randomly Assigned to Receive Varenicline Versus Placebo. (time frame: 8-weeks). 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 14 Mar 2013.