- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00713479
An Assessment of the Safety of Varenicline in Methamphetamine-dependent Volunteers
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.
Study Overview
Status
Intervention / Treatment
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 Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
California
-
Los Angeles, California, United States, 90095
- UCLA NPI
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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;
- 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.
Exclusion Criteria:
- 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;
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Sugar pill
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.
|
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
Other Names:
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
Other Names:
|
Active Comparator: Varenicline
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.
|
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
Other Names:
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
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
15 minute intervals
|
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.
|
15 minute intervals
|
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.
|
15 minute intervals
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Depression
Time Frame: Daily
|
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.
|
Daily
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Edythe D London, PhD, UCLA NPI
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Mental Disorders
- Chemically-Induced Disorders
- Substance-Related Disorders
- Compulsive Behavior
- Impulsive Behavior
- Behavior, Addictive
- Amphetamine-Related Disorders
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Cholinergic Agents
- Nicotinic Agonists
- Cholinergic Agonists
- Varenicline
Other Study ID Numbers
- 18185-PI-EDL-V
- DPMC (Other Identifier: NIDA)
- P50DA018185 (U.S. NIH Grant/Contract)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Methamphetamine Addiction
-
California Pacific Medical Center Research InstituteCompletedMethamphetamine AddictionUnited States
-
Baylor College of MedicineUniversity of California, Los AngelesCompletedMethamphetamine AddictionUnited States
-
California Pacific Medical Center Research InstituteCompletedMethamphetamine AddictionUnited States
-
Ruijin HospitalUnknownTreatment Methamphetamine AddictionChina
-
Centre hospitalier de l'Université de Montréal...Canadian Institutes of Health Research (CIHR)RecruitingAddiction | Methamphetamine-dependence | Addiction, Substance | Methamphetamine AbuseCanada
-
Shanghai Mental Health CenterCompleted
-
Shanghai Mental Health CenterActive, not recruiting
-
Shanghai Mental Health CenterCompleted
-
California Pacific Medical Center Research InstituteCompleted
-
Ryan M. CarnahanUniversity of Utah; University of New MexicoCompletedMethamphetamine-dependence | Stimulant Dependence | Addiction, DrugUnited States
Clinical Trials on Varenicline, then placebo
-
Oyster Point Pharma, Inc.CompletedHealthy SubjectsUnited States
-
Lung InstituteWithdrawnCOPD | Chronic Bronchitis | Emphysema or COPDUnited States
-
Bangor UniversityCompleted
-
Odense University HospitalCompleted
-
Centre Hospitalier Universitaire de Saint EtienneCompleted
-
University of RochesterEndo PharmaceuticalsTerminated
-
Legacy Health SystemUnknownMenopause | Climacteric; Menorrhagia, MenopausalUnited States
-
Bridge Biotherapeutics, Inc.KCRN Research, LLCTerminated
-
The University of Texas Health Science Center at...National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National...CompletedDiabetes Mellitus, Type 2United States