Methamphetamine AddictionPhase 1NCT00713479
An Assessment of the Safety of Varenicline in Methamphetamine-dependent Volunteers
A Phase 1 study of Methamphetamine Addiction and Crystal Meth Addiction, run by University of California, Los Angeles at 1 site in United States.
Trial summary
More people worldwide use amphetamine-type stimulants than any illicit drug besides cannabis, and methamphetamine (MA) abuse and dependence is the fastest growing drug problem in the United States. Much work remains in identifying an effective pharmacotherapy for MA dependence. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Methamphetamine Addiction, Crystal Meth Addiction, Amphetamine Addiction
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2008to Sep 2009
- Phase
- Phase 1
- 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 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Be English-speaking volunteers who are not seeking treatment at the time of the study;
- Be between 18-55 years of age;
- Meet DSM-IV TR criteria for MA dependence;
- Must be cigarette smokers, defined as smoking 10 or more cigarettes per day by self-report;
- Have a self-reported history of using MA by the smoked or IV route and provide at least one MA-positive urine prior to admission;
- Have vital signs as follows: resting pulse between 50 and 90 bpm, blood pressures between 105-150 mm Hg systolic and 45-90 mm Hg diastolic; this criterion must be met within 2 days of admission;
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- Have hematology and chemistry laboratory tests that are within normal (+/- 10%) limits with the following exceptions: a) liver function tests (total bilirubin, ALT, AST, and alkaline phosphatase) < 3 x the upper limit of normal, and b) kidney function tests (creatinine and BUN) < 2 x the upper limit of normal;
- Have a baseline EKG that demonstrates normal sinus rhythm, normal conduction (including QTc), and no clinically significant arrhythmias;
- Have a medical history and brief physical examination demonstrating no clinically significant contraindications for study participation, in the judgment of the admitting physician or nurse practitioner and the principal investigator.
Who cannot join
- Have any history or evidence suggestive of seizure disorder or brain injury
- Have any previous medically adverse reaction to MA, including loss of consciousness, chest pain, or epileptic seizure
- Have neurological or psychiatric disorders, such as
- psychosis, bipolar illness or major depression as assessed by SCID;
- organic brain disease or dementia assessed by clinical interview;
- history of any psychiatric disorder which would require ongoing treatment or which would make study compliance difficult;
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- history of suicide attempts within the past three months assessed by SCID and/or current suicidal ideation/plan as assessed by SCID;
- Have evidence of clinically significant heart disease or hypertension, as determined by the PI;
- Have a family history in first-degree relatives of early cardiovascular morbidity or mortality, as determined by the PI;
- Have evidence of untreated or unstable medical illness including: neuroendocrine, autoimmune, renal, hepatic, or active infectious disease;
- Have HIV and are currently symptomatic, have a diagnosis of AIDS, or are receiving antiretroviral medication;
- Be pregnant or nursing. Other females must either be unable to conceive (i.e., surgically sterilized, sterile, or post-menopausal) or be using a reliable form of contraception (e.g., abstinence, birth control pills, intrauterine device, condoms, or spermicide). All females must provide negative pregnancy urine tests before study entry, upon hospital admission, and at the end of study participation;
- Have asthma or currently use alpha or beta agonists, theophylline, or other sympathomimetics;
- Have any other illness, condition, or use of psychotropic medications, which in the opinion of the PI and/or the admitting physician or nurse practitioner would preclude safe and/or successful completion of the study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Human Laboratory Assessment of the Safety and Potential Efficacy of Varenicline in Methamphetamine-dependent Volunteers Receiving Methamphetamine
More people worldwide use amphetamine-type stimulants than any illicit drug besides cannabis, and methamphetamine (MA) abuse and dependence is the fastest growing drug problem in the United States. Much work remains in identifying an effective pharmacotherapy for MA dependence. The neurobiological actions produced by MA involve dopamine (DA), serotonin, and norepinephrine, but also include alterations to cholinergic neurotransmitter systems. Candidate compounds that target acetylcholine (ACh) are attractive options for development that have not received adequate attention. Varenicline is a drug that increases the release of DA in the brain and it is logical to assume that it would to some extent compensate for the reduction in these neurotransmitters that occurs in MA withdrawal.
Current research has linked certain genes that are related to neurotransmitters with drug abuse and memory impairment (e.g., A1 allele for the D2 dopamine receptor and catechol-O-methyltransferase). We will take blood samples and test for these genes in order to relate the findings to brain function.
This is a double-blind, placebo-controlled, within-subjects study to determine the safety and tolerability of MA in MA-dependent volunteers treated with varenicline and placebo.
Read the detailed description
Study Procedures:
Study participants are those who meet criteria for MA dependence, who are not seeking treatment, and who also meet criteria for nicotine dependence. Participants will be asked to wear a telemetry device during screening and throughout the study that records heart rate and body temperature. Participants will be required to refrain from smoking at certain times, illicit and prescription drug use for the duration of the study and this will be confirmed with daily urine testing.
The study consists of 30 days or less of outpatient screening. The 2-component inpatient portion of the study lasts a total of 18 days. Participants will be admitted to the GCRC at UCLA for Days 1-10. After the first study day, participants will be randomized to varenicline or matched placebo for 9-days and then discharged from the GCRC. Then, after 2-4 weeks, the same subjects return to the GCRC to be switched to the alternate condition (placebo or varenicline) for the second component of the study, which lasts another 8-days. Each subject is randomized to both varenicline and placebo, so total time commitment is 18 inpatient study days. One follow-up visit is scheduled 2 weeks after completion of both study phases for assessment of delayed adverse events and for final payment.
On the first day of the inpatient procedure, subjects received 10 3mg infusions of methamphetamine over 2.5 hours for assessment of drug tolerability. On day 9 of the first component and day 7 of the second component, subjects received either 10 3mg infusions of saline OR methamphetamine over 2.5 hours. In the afternoon, the infusion was the opposite of the morning condition.
- Being tested
- Varenicline, then placebo, Placebo, then varenicline
- Keywords
- methamphetamine, varenicline, Chantix, stimulant, crystal meth
- Medical subject headings
- Amphetamine-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Varenicline, then placeboDrug
Also called varenicline
Subjects receive MA infusions on certain days first under varenicline (10 days) then under placebo (8 days) after a 14-24 day washout in order to determine study medication safety and tolerability
Placebo, then vareniclineDrug
Also called placebo
Subjects receive MA infusions on certain days first under placebo (10 days) then under varenicline(8 days) after a 14-28 day washout in order to determine study medication safety and tolerability
| Study group | Role | What they receive |
|---|---|---|
| Sugar pill | Placebo comparator | Sugar pill (placebo) drug dosing will begin at 0.5 mg once daily for the first 3 days of condition and will be increased to 0.5 mg twice daily for days 5-6 of this condition, and increased to 1 mg twice daily on days 7-10 of this condition. Receives: Drug: Varenicline, then placebo; Drug: Placebo, then varenicline |
| Varenicline | Active comparator | Varenicline dosing will begin at 0.5 mg once daily for the first 3 days of condition and will be increased to 0.5 mg twice daily for days 5-6 of this condition, and increased to 1 mg twice daily on days 7-10 of this condition. Receives: Drug: Varenicline, then placebo; Drug: Placebo, then varenicline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Systolic Blood Pressure
Systolic blood pressure is evaluated at 15 min intervals under placebo or varenicline in the presence of methamphetamine over 140 minutes post infusion. Data is pooled and the mean and standard deviation are presented.
Measured: 15 minute intervals
Diastolic Blood Pressure
Diastolic blood pressure is evaluated at 15 min intervals under placebo or varenicline in the presence of methamphetamine over 140 minutes post infusion. Data is pooled and the mean and standard deviation are presented.
Measured: 15 minute intervals
Heart Rate
Heart rate is evaluated at 15 min intervals under placebo or varenicline in the presence of methamphetamine over 140 minutes post infusion. Data is pooled and the mean and standard deviation are presented.
Measured: 15 minute intervals
Secondary outcomes (1)
Depression
Using the Beck Depression Index (BDI-II), depression was assessed on a daily basis. The daily mean score during the medication intervention period is presented, with a lower score indicating lower reported depression. The scores range from 0-13: minimal depression; 14-19: mild depression; 20-28: moderate depression; and 29-63: severe depression.
Measured: Daily
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2008 (estimated)
- Study startJul 2008
- Primary completionAug 2009
- Study completionSep 2009
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Methamphetamine AddictionStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 8 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
- Edythe D London, PhD, Principal investigator, UCLA NPI
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00713479
- Sponsor's protocol ID
- 18185-PI-EDL-V
- Other IDs
- P50DA018185, DPMC
- Status last verified
- Feb 2018
- First submitted
- 10 Jul 2008
- Last updated
- 13 Mar 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Zorick T, Sevak RJ, Miotto K, Shoptaw S, Swanson AN, Clement C, De La Garza R 2nd, Newton TF, London ED. Pilot safety evaluation of varenicline for the treatment of methamphetamine dependence. J Exp Pharmacol. 2009 Dec 24;2:13-8. eCollection 2010.
PubMed 27186086
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Human Laboratory Assessment of the Safety and Potential Efficacy of Varenicline in Methamphetamine-dependent Volunteers Receiving Methamphetamine
- ClinicalTrials.gov ID
- NCT00713479
- Acronym / sponsor ID
- 18185-PI-EDL-V
- Keywords
- methamphetamine, varenicline, Chantix, stimulant, crystal meth
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- University of California, Los AngelesUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- Jul 2008
- Primary completion
- Aug 2009 (actual)
- Study completion
- Sep 2009 (actual)
- First posted
- 11 Jul 2008 (estimated)
- Results
- Posted 27 Jan 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
More people worldwide use amphetamine-type stimulants than any illicit drug besides cannabis, and methamphetamine (MA) abuse and dependence is the fastest growing drug problem in the United States. Much work remains in identifying an effective pharmacotherapy for MA dependence. The neurobiological actions produced by MA involve dopamine (DA), serotonin, and norepinephrine, but also include alterations to cholinergic neurotransmitter systems. Candidate compounds that target acetylcholine (ACh) are attractive options for development that have not received adequate attention. Varenicline is a drug that increases the release of DA in the brain and it is logical to assume that it would to some extent compensate for the reduction in these neurotransmitters that occurs in MA withdrawal.
Current research has linked certain genes that are related to neurotransmitters with drug abuse and memory impairment (e.g., A1 allele for the D2 dopamine receptor and catechol-O-methyltransferase). We will take blood samples and test for these genes in order to relate the findings to brain function.
This is a double-blind, placebo-controlled, within-subjects study to determine the safety and tolerability of MA in MA-dependent volunteers treated with varenicline and placebo.
Detailed description
Study Procedures:
Study participants are those who meet criteria for MA dependence, who are not seeking treatment, and who also meet criteria for nicotine dependence. Participants will be asked to wear a telemetry device during screening and throughout the study that records heart rate and body temperature. Participants will be required to refrain from smoking at certain times, illicit and prescription drug use for the duration of the study and this will be confirmed with daily urine testing.
The study consists of 30 days or less of outpatient screening. The 2-component inpatient portion of the study lasts a total of 18 days. Participants will be admitted to the GCRC at UCLA for Days 1-10. After the first study day, participants will be randomized to varenicline or matched placebo for 9-days and then discharged from the GCRC. Then, after 2-4 weeks, the same subjects return to the GCRC to be switched to the alternate condition (placebo or varenicline) for the second component of the study, which lasts another 8-days. Each subject is randomized to both varenicline and placebo, so total time commitment is 18 inpatient study days. One follow-up visit is scheduled 2 weeks after completion of both study phases for assessment of delayed adverse events and for final payment.
On the first day of the inpatient procedure, subjects received 10 3mg infusions of methamphetamine over 2.5 hours for assessment of drug tolerability. On day 9 of the first component and day 7 of the second component, subjects received either 10 3mg infusions of saline OR methamphetamine over 2.5 hours. In the afternoon, the infusion was the opposite of the morning condition.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sugar pill | Placebo comparator | Drug: Varenicline, then placebo, Drug: Placebo, then vareniclineSugar pill (placebo) drug dosing will begin at 0.5 mg once daily for the first 3 days of condition and will be increased to 0.5 mg twice daily for days 5-6 of this condition, and increased to 1 mg twice daily on days 7-10 of this condition. |
| Varenicline | Active comparator | Drug: Varenicline, then placebo, Drug: Placebo, then vareniclineVarenicline dosing will begin at 0.5 mg once daily for the first 3 days of condition and will be increased to 0.5 mg twice daily for days 5-6 of this condition, and increased to 1 mg twice daily on days 7-10 of this condition. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Be English-speaking volunteers who are not seeking treatment at the time of the study;
- Be between 18-55 years of age;
- Meet DSM-IV TR criteria for MA dependence;
- Must be cigarette smokers, defined as smoking 10 or more cigarettes per day by self-report;
- Have a self-reported history of using MA by the smoked or IV route and provide at least one MA-positive urine prior to admission;
Key exclusion criteria (14 listed)
- Have any history or evidence suggestive of seizure disorder or brain injury
- Have any previous medically adverse reaction to MA, including loss of consciousness, chest pain, or epileptic seizure
- Have neurological or psychiatric disorders, such as
- Have evidence of clinically significant heart disease or hypertension, as determined by the PI;
- Have a family history in first-degree relatives of early cardiovascular morbidity or mortality, as determined by the PI;
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 |
|---|---|---|
| Varenicline, then placeboAlso: vareniclineSubjects receive MA infusions on certain days first under varenicline (10 days) then under placebo (8 days) after a 14-24 day washout in order to determine study medication safety and tolerability | Drug | Sugar pill, Varenicline |
| Placebo, then vareniclineAlso: placeboSubjects receive MA infusions on certain days first under placebo (10 days) then under varenicline(8 days) after a 14-28 day washout in order to determine study medication safety and tolerability | Drug | Sugar pill, Varenicline |
Primary outcome
Systolic Blood Pressure
Time frame: 15 minute intervals
Systolic blood pressure is evaluated at 15 min intervals under placebo or varenicline in the presence of methamphetamine over 140 minutes post infusion. Data is pooled and the mean and standard deviation are presented.
Diastolic Blood Pressure
Time frame: 15 minute intervals
Diastolic blood pressure is evaluated at 15 min intervals under placebo or varenicline in the presence of methamphetamine over 140 minutes post infusion. Data is pooled and the mean and standard deviation are presented.
Heart Rate
Time frame: 15 minute intervals
Heart rate is evaluated at 15 min intervals under placebo or varenicline in the presence of methamphetamine over 140 minutes post infusion. Data is pooled and the mean and standard deviation are presented.
1 secondary outcome
Depression
Time frame: Daily
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 27186086Zorick T, Sevak RJ, Miotto K, Shoptaw S, Swanson AN, Clement C, De La Garza R 2nd, Newton TF, London ED. Pilot safety evaluation of varenicline for the treatment of methamphetamine dependence. J Exp Pharmacol. 2009 Dec 24;2:13-8. eCollection 2010.
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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.
Edythe D London, PhD principal investigator
UCLA NPI
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 of Methamphetamine Addiction and Crystal Meth Addiction, 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 9 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 13 Mar 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. 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 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?
Yes. Results are posted in the registry (first posted 27 Jan 2014). 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?
Systolic Blood Pressure (time frame: 15 minute intervals). 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 NCT00713479, which also lists 1 linked publication.
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 13 Mar 2018.