Amphetamine DependenceNCT00600145
Dose Response of Mirtazapine to Methamphetamine Induced Interest, Mood Elevation and Reward
A study testing Mirtazapine in people with Amphetamine Dependence, run by University of Virginia at 1 site in United States.
Trial summary
The primary purpose of this study is to determine if Mirtazapine will produce a decrease in interest in the drug, a decrease in mood elevation, and/or a decrease in reward when given before methamphetamine compared to placebo. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Amphetamine Dependence
- What is being tested?
- Mirtazapine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2007to Jul 2010
- Phase
- Interventional
- 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 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 18 -45 years old
- healthy human volunteers
- no history of pre-existing physical (including cardiovascular) illness
- no history of drug abuse or dependence (defined below)
- ability to read and write
Who cannot join
- pregnant
- any psychotropic medication
- criteria for active substance abuse or dependence based on the DSM-IV: For substance abuse: A maladaptive pattern of substance use leading to clinically significant impairment or distress, as manifested by one (or more) of the following, occurring within a 12-month period:
- recurrent substance use resulting in a failure to fulfill major role obligations at work, school, home (e.g., repeated absences or poor work performance related to substance use; substance-related absences, suspensions, or expulsions from school; neglect of children or household)
- recurrent substance use in situations in which it is physically hazardous (e.g., driving an automobile or operating a machine when impaired by substance use)
- recurrent substance-related legal problems (e.g., arrests for substance-related disorderly conduct)
Show all 51Show fewer
- continued substance use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of the substance (e.g., arguments with spouse about consequences of intoxication, physical fights)
- The symptoms have never met the criteria for Substance Dependence for this class of substances.
- For substance dependence: A maladaptive pattern of substance use, leading to clinically significant impairment or distress, as manifested by three (or more) of the following, occurring at any time in the same 12-month period:
- tolerance, as defined by either of the following:
- a need for markedly increased amounts of the substance to achieve intoxication or desired effect
- markedly diminished effect with continued use of the same amount of substance
- withdrawal, as manifested by either of the following:
- the characteristic withdrawal syndrome for the substance
- the same (or a closely related) substance is taken to relieve or avoid withdrawal symptoms
- the substance is often taken in larger amounts or over a longer period than was intended
- there is a persistent desire or unsuccessful efforts to cut down or control substance use
- a great deal of time is spent in activities to obtain the substance, use the substance, or recover from its effects
- important social, occupational or recreational activities are given up or reduced because of substance use
- the substance use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the substance (e.g., continued drinking despite recognition that an ulcer was made worse by alcohol consumption) on any stimulant medication including:
- Amphetamine (Adderall®, Adderall XR®)
- Dextroamphetamine (Dexedrine®)
- Methamphetamine (Desoxyn®)
- Dexmethylphenidate (Focalin®, Focalin® XR)
- Diethylpropion (Tenuate®, Tenuate Dospan®)
- Methylphenidate (Metadate CD®, Ritalin LA®, Methylin®, Ritalin®, Metadate ER®, Ritalin SR®, Methylin ER®, Daytrana®, Concerta®)
- Pemoline (Cylert®)
- Benzphetamine (Didrex®)
- Phendimetrazine (Adipost®, Bontril®, Melfiat®, Prelu-2®, X-Trozine LA®, Bontril PDM®, Obezine®, Obezine caplets) ®
- Phentermine (Ionamin®, Phentride®, Teramine®, Adipex-P®)
- Sibutramine (Meridia®)
- Caffeine (No Doz®, Quick-Pep®, Vivarin®, Caffedrine®,Caffeine and sodium benzoate inj, Cafcit®)
- Doxapram (Dopram®)
- Modafinil (Provigil®)
- Cocaine
- MDMA (Ecstasy)
- MDA
- history of hypertension (BP > 140/90 mm Hg) or systolic hypotension (BP <90/75 mm Hg).
- Subjects with resting pulse rate >90/min.
- any active medical illness
- Subjects known to have clinically significant medical conditions, as determined by complete physical examination, or, a past or current history of the following conditions (including but not limited to):
- cerebrovascular accident or transient ischemic attack;
- ischemic heart disease or myocardial infarction;
- symptomatic coronary artery disease or peripheral vascular disease;
- malignancy or history of malignancy within the past 5 years (except basal cell carcinoma);
- renal disease and/or impaired renal function as defined by subjects with a creatinine clearance of £60 ml/min/24hrs;
- diseases of the gastrointestinal system including active liver disease or current active hepatitis;
- subjects with AST and/or ALT >2 times the upper limit of the normal range and/or an increased serum bilirubin >2 times the upper limit of normal at screening;
- pulmonary disorders
- endocrinological disorders including thyroid disorders;
- gross neurological disorders including subjects with seizure disorders and subjects with progressive or degenerative neurological disorders (e.g., multiple sclerosis)
Trial locations and contacts
1 site in 1 country.
United States1 site
Universiyt of Virginia
Charlottesville, Virginia, 22908
About this study
The primary purpose of this study is to determine if Mirtazapine will produce a decrease in interest in the drug, a decrease in mood elevation, and/or a decrease in reward when given before methamphetamine compared to placebo.
Participants will be screened with a psychiatric interview, medical history and physical, laboratory tests, drug of abuse screen and, if female, a urine pregnancy test. They will be provided written informed consent. They will be studied in a within-subjects examination of the subjective mood responses of mirtazapine and methamphetamine. Interactions between methamphetamine and mirtazapine will be assessed by pharmacokinetic studies. Each participant will be introduced to rating scales and cognitive tasks described below. Participants will remain in the research unit for 5 hours on each day that they receive study medication or placebo. They will spend five days in total on the research unit, one day separated by at least one day; then in two day blocks separated by at least one day from another two day block. A venous catheter will be placed for blood draws. Blood pressures and heart rates will be recorded and assessed. Participants will be randomized and double blinded to receive either placebo or mirtazapine orally two hours prior to the administration of randomized and double blinded methamphetamine or placebo in order to have the peak effects of the drugs overlap. VAS-mood, ARCI, GRS, POMS and POMS-E, neurocognitive tasks Trails A and B and Symbol digits modalities test will be administered prior to the mirtazapine or placebo dose, and repeated after the administration of methamphetamine or placebo. After the administration of methamphetamine or placebo, vital signs will be assessed every 15 minutes and the measures will be repeated until 120 minutes have passed from the initial dose of methamphetamine or placebo. Blood will be drawn at one, three and four hour marks for pharmacokinetic testing. This will be repeated on each testing day.
Read the detailed description
Methamphetamine dependence is a major health problem in the US. Methamphetamine's reinforcing effects associated with its abuse liability depend upon activation of the cortico-mesolimbic dopamine (CMDA) system. Medications that antagonize CMDA function might have therapeutic potential Mirtazapine appears to affect this pathway. Mirtazapine works through serotinergic (5-HT) mechanisms 5HT 2 and 3, alpha 2 and H1 antagonist and has been noted to decrease excitatory responses in methamphetamine challenged animals. Mirtazapine increases dopamine release in the prefrontal cortex by 5HT receptor activation. Additionally, in a randomized, placebo controlled trial; individuals taking mirtazapine for amphetamine detoxification were found to have significant improvements in hyper arousal and anxiety subset score when discontinuing the stimulant. Methamphetamine has been given safely to healthy human volunteers in other studies.
We propose to conduct the first preliminary human laboratory study to determine if mirtazapine 15 mg diminishes methamphetamine (20 mg) induced positive subjective interest, mood elevation and reinforcing value. This dose of methamphetamine has been used by other investigators in healthy volunteers.
This preliminary trial is the first in a sequence of studies to characterize the dose dependent effects of mirtazapine as a treatment agent for methamphetamine dependence. If this study is successful, it would afford us a scientific platform and rationale for progressing with testing efficacy for mirtazapine among methamphetamine dependent individuals both in the human laboratory and in clinical trials. The primary objective of this study is to evaluate systematically the neurobehavioral basis and dose-response effects of mirtazapine acutely on methamphetamine-induced interest, mood elevation and reward. This study employs a well-validated, state-of-the-art, human laboratory technique to determine the extent to which mirtazapine blocks methamphetamine induced euphoria, reinforcement, and cue craving in healthy volunteers tested in a controlled hospital environment under medical supervision.
- Conditions
- Amphetamine Dependence
- Being tested
- Mirtazapine, Placebo
- Keywords
- Human volunteers, amphetamine dependence
- 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.
MirtazapineDrug
Also called Remeron
15 mg Mirtazapine is administered followed 2 hours later by 20 mg of methamphetamine / placebo (administered at each testing visit)
PlaceboOther
Placebo
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Mirtazapine Receives: Drug: Mirtazapine |
| 2 | Placebo comparator | Placebo Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
extent to which mirtazapine reduces methamphetamine induced mood elevation, reward, and interest
Measured: At each study visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2008 (estimated)
- Study startSep 2007
- Primary completionDec 2009 (estimated)
- Study completionJul 2010 (estimated)
Why it stopped: PI decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Amphetamine DependenceStudies of the same condition, open and under way.
- More trials run by University of VirginiaThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Virginia
- Sponsor type
- University, hospital or other
- Collaborators
- American Association of Chairs of Departments of Psychiatry
- Investigators
- Gabrielle Marzani-Nissen, MD, Principal investigator, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00600145
- Sponsor's protocol ID
- 13222
- Status last verified
- Apr 2011
- First submitted
- 10 Jan 2008
- Last updated
- 27 Apr 2011
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dose Response of Mirtazapine to Methamphetamine Induced Interest, Mood Elevation and Reward
- ClinicalTrials.gov ID
- NCT00600145
- Acronym / sponsor ID
- 13222
- Conditions
- Amphetamine Dependence
- Keywords
- Human volunteers, amphetamine dependence
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: PI decision
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of VirginiaUniversity, hospital or other
- Collaborators
- American Association of Chairs of Departments of Psychiatry
- Study start
- Sep 2007
- Primary completion
- Dec 2009 (estimated)
- Study completion
- Jul 2010 (estimated)
- First posted
- 24 Jan 2008 (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 primary purpose of this study is to determine if Mirtazapine will produce a decrease in interest in the drug, a decrease in mood elevation, and/or a decrease in reward when given before methamphetamine compared to placebo.
Participants will be screened with a psychiatric interview, medical history and physical, laboratory tests, drug of abuse screen and, if female, a urine pregnancy test. They will be provided written informed consent. They will be studied in a within-subjects examination of the subjective mood responses of mirtazapine and methamphetamine. Interactions between methamphetamine and mirtazapine will be assessed by pharmacokinetic studies. Each participant will be introduced to rating scales and cognitive tasks described below. Participants will remain in the research unit for 5 hours on each day that they receive study medication or placebo. They will spend five days in total on the research unit, one day separated by at least one day; then in two day blocks separated by at least one day from another two day block. A venous catheter will be placed for blood draws. Blood pressures and heart rates will be recorded and assessed. Participants will be randomized and double blinded to receive either placebo or mirtazapine orally two hours prior to the administration of randomized and double blinded methamphetamine or placebo in order to have the peak effects of the drugs overlap. VAS-mood, ARCI, GRS, POMS and POMS-E, neurocognitive tasks Trails A and B and Symbol digits modalities test will be administered prior to the mirtazapine or placebo dose, and repeated after the administration of methamphetamine or placebo. After the administration of methamphetamine or placebo, vital signs will be assessed every 15 minutes and the measures will be repeated until 120 minutes have passed from the initial dose of methamphetamine or placebo. Blood will be drawn at one, three and four hour marks for pharmacokinetic testing. This will be repeated on each testing day.
Detailed description
Methamphetamine dependence is a major health problem in the US. Methamphetamine's reinforcing effects associated with its abuse liability depend upon activation of the cortico-mesolimbic dopamine (CMDA) system. Medications that antagonize CMDA function might have therapeutic potential Mirtazapine appears to affect this pathway. Mirtazapine works through serotinergic (5-HT) mechanisms 5HT 2 and 3, alpha 2 and H1 antagonist and has been noted to decrease excitatory responses in methamphetamine challenged animals. Mirtazapine increases dopamine release in the prefrontal cortex by 5HT receptor activation. Additionally, in a randomized, placebo controlled trial; individuals taking mirtazapine for amphetamine detoxification were found to have significant improvements in hyper arousal and anxiety subset score when discontinuing the stimulant. Methamphetamine has been given safely to healthy human volunteers in other studies.
We propose to conduct the first preliminary human laboratory study to determine if mirtazapine 15 mg diminishes methamphetamine (20 mg) induced positive subjective interest, mood elevation and reinforcing value. This dose of methamphetamine has been used by other investigators in healthy volunteers.
This preliminary trial is the first in a sequence of studies to characterize the dose dependent effects of mirtazapine as a treatment agent for methamphetamine dependence. If this study is successful, it would afford us a scientific platform and rationale for progressing with testing efficacy for mirtazapine among methamphetamine dependent individuals both in the human laboratory and in clinical trials. The primary objective of this study is to evaluate systematically the neurobehavioral basis and dose-response effects of mirtazapine acutely on methamphetamine-induced interest, mood elevation and reward. This study employs a well-validated, state-of-the-art, human laboratory technique to determine the extent to which mirtazapine blocks methamphetamine induced euphoria, reinforcement, and cue craving in healthy volunteers tested in a controlled hospital environment under medical supervision.
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 |
|---|---|---|
| 1 | Experimental | Drug: MirtazapineMirtazapine |
| 2 | Placebo comparator | Other: PlaceboPlacebo |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 18 -45 years old
- healthy human volunteers
- no history of pre-existing physical (including cardiovascular) illness
- no history of drug abuse or dependence (defined below)
- ability to read and write
Key exclusion criteria (51 listed)
- pregnant
- any psychotropic medication
- criteria for active substance abuse or dependence based on the DSM-IV: For substance abuse: A maladaptive pattern of substance use leading to clinically significant impairment or distress, as manifested by one (or more) of the following, occurring within a 12-month period:
- The symptoms have never met the criteria for Substance Dependence for this class of substances.
- For substance dependence: A maladaptive pattern of substance use, leading to clinically significant impairment or distress, as manifested by three (or more) of the following, occurring at any time in the same 12-month period:
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 |
|---|---|---|
| MirtazapineAlso: Remeron15 mg Mirtazapine is administered followed 2 hours later by 20 mg of methamphetamine / placebo (administered at each testing visit) | Drug | 1 |
| PlaceboPlacebo | Other | 2 |
Primary outcome
extent to which mirtazapine reduces methamphetamine induced mood elevation, reward, and interest
Time frame: At each study visit
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2011.
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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.
Gabrielle Marzani-Nissen, MD principal investigator
University of Virginia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Mirtazapine in people with Amphetamine Dependence, run by University of Virginia 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 51 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: withdrawn, as of the sponsor's last update on 27 Apr 2011. 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.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
extent to which mirtazapine reduces methamphetamine induced mood elevation, reward, and interest (time frame: At each study visit). 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 27 Apr 2011.