Monoamine Antagonist Therapies for Methamphetamine Abuse Prazosin (MATMA)

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Arkansas
ClinicalTrials.gov Identifier:
NCT01178138
First received: August 4, 2010
Last updated: July 3, 2013
Last verified: July 2013
  Purpose

This protocol will test the safety, effectiveness and the metabolism and action of prazosin as a potential therapy for methamphetamine abuse. This will be accomplished by performing a series of human laboratory studies. In each of these studies, the safety and effectiveness of the test medication (prazosin) in the treatment of methamphetamine effects will be determined. The study hypothesis is that prazosin will block the methamphetamine receptor function, reducing the reinforcing effects of central nervous system effects in humans.


Condition Intervention Phase
Non-treatment Seeking Methamphetamine Users
Drug: oral placebo and methamphetamine 20mg po
Drug: Prazosin 1mg po and oral methamphetamine placebo
Drug: Prazosin 1mg po and Methamphetamine 20mg po
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Health Services Research
Official Title: Monoamine Antagonist Therapies for Methamphetamine Abuse Prazosin

Resource links provided by NLM:


Further study details as provided by University of Arkansas:

Primary Outcome Measures:
  • Specific Aim 1 - Self-report and cognitive performance effects. [ Time Frame: up to one hour before study medication is given ] [ Designated as safety issue: No ]

    Specific Aim 1 - Self-report and cognitive performance effects.

    Self-Report:three questionaires measuring effects of five subclasses of drugs, degree of like or dislike for study drug, and mood effects of study drug.

    Cognitive Performance:three tests measuring psychomotor speed, manipulation of information, incidental learning of digit-symbol pairs and sustained effort,attention, sequencing, mental flexability, and ability to ignore irrelevant information.


  • Specific Aim 1 - Self-report and cognitive performance effects. [ Time Frame: 30 min ] [ Designated as safety issue: No ]

    Specific Aim 1 - Self-report and cognitive performance effects.

    Self-Report:three questionaires measuring effects of five subclasses of drugs, degree of like or dislike for study drug, and mood effects of study drug.

    Cognitive Performance:three tests measuring psychomotor speed, manipulation of information, incidental learning of digit-symbol pairs and sustained effort,attention, sequencing, mental flexability, and ability to ignore irrelevant information.


  • Specific Aim 1 - Self-report and cognitive performance effects. [ Time Frame: 1 hour ] [ Designated as safety issue: No ]

    Specific Aim 1 - Self-report and cognitive performance effects.

    Self-Report:three questionaires measuring effects of five subclasses of drugs, degree of like or dislike for study drug, and mood effects of study drug.

    Cognitive Performance:three tests measuring psychomotor speed, manipulation of information, incidental learning of digit-symbol pairs and sustained effort,attention, sequencing, mental flexability, and ability to ignore irrelevant information.


  • Specific Aim 1 - Self-report and cognitive performance effects. [ Time Frame: 90 minute ] [ Designated as safety issue: No ]

    Specific Aim 1 - Self-report and cognitive performance effects.

    Self-Report:three questionaires measuring effects of five subclasses of drugs, degree of like or dislike for study drug, and mood effects of study drug.

    Cognitive Performance:three tests measuring psychomotor speed, manipulation of information, incidental learning of digit-symbol pairs and sustained effort,attention, sequencing, mental flexability, and ability to ignore irrelevant information.


  • Specific Aim 1 - Self-report and cognitive performance effects. [ Time Frame: 2 hour ] [ Designated as safety issue: No ]

    Specific Aim 1 - Self-report and cognitive performance effects.

    Self-Report:three questionaires measuring effects of five subclasses of drugs, degree of like or dislike for study drug, and mood effects of study drug.

    Cognitive Performance:three tests measuring psychomotor speed, manipulation of information, incidental learning of digit-symbol pairs and sustained effort,attention, sequencing, mental flexability, and ability to ignore irrelevant information.


  • Specific Aim 1 - Self-report and cognitive performance effects. [ Time Frame: 150 minute ] [ Designated as safety issue: No ]

    Specific Aim 1 - Self-report and cognitive performance effects.

    Self-Report:three questionaires measuring effects of five subclasses of drugs, degree of like or dislike for study drug, and mood effects of study drug.

    Cognitive Performance:three tests measuring psychomotor speed, manipulation of information, incidental learning of digit-symbol pairs and sustained effort,attention, sequencing, mental flexability, and ability to ignore irrelevant information.


  • Specific Aim 1 - Self-report and cognitive performance effects. [ Time Frame: 3 hour ] [ Designated as safety issue: No ]

    Specific Aim 1 - Self-report and cognitive performance effects.

    Self-Report:three questionaires measuring effects of five subclasses of drugs, degree of like or dislike for study drug, and mood effects of study drug.

    Cognitive Performance:three tests measuring psychomotor speed, manipulation of information, incidental learning of digit-symbol pairs and sustained effort,attention, sequencing, mental flexability, and ability to ignore irrelevant information.


  • Specific Aim 1 - Self-report and cognitive performance effects. [ Time Frame: 3 hour 30 minute ] [ Designated as safety issue: No ]

    Specific Aim 1 - Self-report and cognitive performance effects.

    Self-Report:three questionaires measuring effects of five subclasses of drugs, degree of like or dislike for study drug, and mood effects of study drug.

    Cognitive Performance:three tests measuring psychomotor speed, manipulation of information, incidental learning of digit-symbol pairs and sustained effort,attention, sequencing, mental flexability, and ability to ignore irrelevant information.


  • Specific Aim 1 - Self-report and cognitive performance effects. [ Time Frame: 4 hour ] [ Designated as safety issue: No ]

    Specific Aim 1 - Self-report and cognitive performance effects.

    Self-Report:three questionaires measuring effects of five subclasses of drugs, degree of like or dislike for study drug, and mood effects of study drug.

    Cognitive Performance:three tests measuring psychomotor speed, manipulation of information, incidental learning of digit-symbol pairs and sustained effort,attention, sequencing, mental flexability, and ability to ignore irrelevant information.


  • Specific Aim 1 - Self-report and cognitive performance effects. [ Time Frame: 5 hour ] [ Designated as safety issue: No ]

    Specific Aim 1 - Self-report and cognitive performance effects.

    Self-Report:three questionaires measuring effects of five subclasses of drugs, degree of like or dislike for study drug, and mood effects of study drug.

    Cognitive Performance:three tests measuring psychomotor speed, manipulation of information, incidental learning of digit-symbol pairs and sustained effort,attention, sequencing, mental flexability, and ability to ignore irrelevant information.


  • Specific Aim 1 - Self-report and cognitive performance effects. [ Time Frame: 6 hour ] [ Designated as safety issue: No ]

    Specific Aim 1 - Self-report and cognitive performance effects.

    Self-Report:three questionaires measuring effects of five subclasses of drugs, degree of like or dislike for study drug, and mood effects of study drug.

    Cognitive Performance:three tests measuring psychomotor speed, manipulation of information, incidental learning of digit-symbol pairs and sustained effort,attention, sequencing, mental flexability, and ability to ignore irrelevant information.


  • Specific Aim 1 - Self-report and cognitive performance effects. [ Time Frame: 7 hour ] [ Designated as safety issue: No ]

    Specific Aim 1 - Self-report and cognitive performance effects.

    Self-Report:three questionaires measuring effects of five subclasses of drugs, degree of like or dislike for study drug, and mood effects of study drug.

    Cognitive Performance:three tests measuring psychomotor speed, manipulation of information, incidental learning of digit-symbol pairs and sustained effort,attention, sequencing, mental flexability, and ability to ignore irrelevant information.



Secondary Outcome Measures:
  • Assessment of CV Effects [ Time Frame: up to one hour before study medication is given ] [ Designated as safety issue: No ]
    temperature, heart rate, respiration, pulse oximetry, blood pressure, non-invasive cardiac monitor data-cardiac output, systemic vascular resistance, Orthostatic measurements to be taken hourly at the 50 minute timepoint for 4 hours.

  • Assessment of CV Effects [ Time Frame: 15 minutes post-dose ] [ Designated as safety issue: No ]
    temperature, heart rate, respiration, pulse oximetry, blood pressure, non-invasive cardiac monitor data-cardiac output, systemic vascular resistance, Orthostatic measurements to be taken hourly at the 50 minute timepoint for 4 hours.

  • Assessment of CV Effects [ Time Frame: 45 minutes post-dose ] [ Designated as safety issue: No ]
    temperature, heart rate, respiration, pulse oximetry, blood pressure, non-invasive cardiac monitor data-cardiac output, systemic vascular resistance, Orthostatic measurements to be taken hourly at the 50 minute timepoint for 4 hours.

  • Assessment of CV Effects [ Time Frame: 1 hour 15 minutes post dose ] [ Designated as safety issue: No ]
    temperature, heart rate, respiration, pulse oximetry, blood pressure, non-invasive cardiac monitor data-cardiac output, systemic vascular resistance, Orthostatic measurements to be taken hourly at the 50 minute timepoint for 4 hours.

  • Assessment of CV Effects [ Time Frame: 1 hour 45 minutes post dose ] [ Designated as safety issue: No ]
    temperature, heart rate, respiration, pulse oximetry, blood pressure, non-invasive cardiac monitor data-cardiac output, systemic vascular resistance, Orthostatic measurements to be taken hourly at the 50 minute timepoint for 4 hours.

  • Assessment of CV Effects [ Time Frame: 2 hour 15 minutes post-dose ] [ Designated as safety issue: No ]
    temperature, heart rate, respiration, pulse oximetry, blood pressure, non-invasive cardiac monitor data-cardiac output, systemic vascular resistance, Orthostatic measurements to be taken hourly at the 50 minute timepoint for 4 hours.

  • Assessment of CV Effects [ Time Frame: 2 hour 45 minutes post-dose ] [ Designated as safety issue: No ]
    temperature, heart rate, respiration, pulse oximetry, blood pressure, non-invasive cardiac monitor data-cardiac output, systemic vascular resistance, Orthostatic measurements to be taken hourly at the 50 minute timepoint for 4 hours.

  • Assessment of CV Effects [ Time Frame: 3 hour 15 minutes post dose ] [ Designated as safety issue: No ]
    temperature, heart rate, respiration, pulse oximetry, blood pressure, non-invasive cardiac monitor data-cardiac output, systemic vascular resistance, Orthostatic measurements to be taken hourly at the 50 minute timepoint for 4 hours.

  • Assessment of CV Effects [ Time Frame: 3 hour 45 minutes post-dose ] [ Designated as safety issue: No ]
    temperature, heart rate, respiration, pulse oximetry, blood pressure, non-invasive cardiac monitor data-cardiac output, systemic vascular resistance, Orthostatic measurements to be taken hourly at the 50 minute timepoint for 4 hours.

  • Assessment of CV Effects [ Time Frame: 4 hour 15 minutes post-dose ] [ Designated as safety issue: No ]
    temperature, heart rate, respiration, pulse oximetry, blood pressure, non-invasive cardiac monitor data-cardiac output, systemic vascular resistance, Orthostatic measurements to be taken hourly at the 50 minute timepoint for 4 hours.

  • Assessment of CV Effects [ Time Frame: 4 hour 45 minutes post-dose ] [ Designated as safety issue: No ]
    temperature, heart rate, respiration, pulse oximetry, blood pressure, non-invasive cardiac monitor data-cardiac output, systemic vascular resistance, Orthostatic measurements to be taken hourly at the 50 minute timepoint for 4 hours.

  • Assessment of CV Effects [ Time Frame: 5 hour 15 minutes post-dose ] [ Designated as safety issue: No ]
    temperature, heart rate, respiration, pulse oximetry, blood pressure, non-invasive cardiac monitor data-cardiac output, systemic vascular resistance, Orthostatic measurements to be taken hourly at the 50 minute timepoint for 4 hours.

  • Assessment of CV Effects [ Time Frame: 5 hour 45 minutes post-dose ] [ Designated as safety issue: No ]
    temperature, heart rate, respiration, pulse oximetry, blood pressure, non-invasive cardiac monitor data-cardiac output, systemic vascular resistance, Orthostatic measurements to be taken hourly at the 50 minute timepoint for 4 hours.

  • Assessment of CV Effects [ Time Frame: 6 hour 15 minutes post-dose ] [ Designated as safety issue: No ]
    temperature, heart rate, respiration, pulse oximetry, blood pressure, non-invasive cardiac monitor data-cardiac output, systemic vascular resistance, Orthostatic measurements to be taken hourly at the 50 minute timepoint for 4 hours.

  • Assessment of CV Effects [ Time Frame: 6 hour 45 minutes post-dose ] [ Designated as safety issue: No ]
    temperature, heart rate, respiration, pulse oximetry, blood pressure, non-invasive cardiac monitor data-cardiac output, systemic vascular resistance, Orthostatic measurements to be taken hourly at the 50 minute timepoint for 4 hours.

  • Assessment of CV Effects [ Time Frame: 7 hour 15 minutes post-dose ] [ Designated as safety issue: No ]
    temperature, heart rate, respiration, pulse oximetry, blood pressure, non-invasive cardiac monitor data-cardiac output, systemic vascular resistance, Orthostatic measurements to be taken hourly at the 50 minute timepoint for 4 hours.

  • Analysis of Drug Concentrations in Human Serum Samples and Assessment of Pharmacokinetic Effects [ Time Frame: up to immediately before study medication is given ] [ Designated as safety issue: No ]
    Determination of 24-OH-cholesterol will be assessed with screening lab samples then pharmacokinetic and pharmacodynamic analyses for meth concentrations with the above timepoints

  • Analysis of Drug Concentrations in Human Serum Samples and Assessment of Pharmacokinetic Effects [ Time Frame: 2 hours past Methamphetamine dose ] [ Designated as safety issue: No ]
    Determination of 24-OH-cholesterol will be assessed with screening lab samples then pharmacokinetic and pharmacodynamic analyses for meth concentrations with the above timepoints

  • Analysis of Drug Concentrations in Human Serum Samples and Assessment of Pharmacokinetic Effects [ Time Frame: 4 hours post Methamphetamine dose ] [ Designated as safety issue: No ]
    Determination of 24-OH-cholesterol will be assessed with screening lab samples then pharmacokinetic and pharmacodynamic analyses for meth concentrations with the above timepoints


Enrollment: 32
Study Start Date: December 2009
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: oral placebo and methamphetamine 20mg po
The order of placebo vs. active medication will be randomized.
Drug: oral placebo and methamphetamine 20mg po
Methamphetamine 20mg po will be given 30 minutes after oral placebo.
Other Name: meth
Active Comparator: Prazosin 1mg po + Methamphetamine placebo po
The order of placebo vs. active medication will be randomized.
Drug: Prazosin 1mg po and oral methamphetamine placebo
Prazosin 1mg orally followed by methamphetamine placebo po in thirty minutes.
Other Names:
  • Minipress
  • meth
Active Comparator: Prazosin 1mg po + Methamphetamine 20mg po
The order of placebo vs. active medication will be randomized.
Drug: Prazosin 1mg po and Methamphetamine 20mg po
Oral Prazosin 1mg given followed in thirty minutes by oral Methamphetamine 20mg
Other Names:
  • Minipress
  • Meth

Detailed Description:

Methamphetamine (METH) use has increased in the US and worldwide in the past years. Although associated with profound medical, psychiatric, legal, and social problems, no effective medicines for METH abuse have been identified or approved for human use. It is vitally important to identify compounds that alter METH effects without increasing the risk of METH toxicity. While the brain chemical transmitter dopamine plays a major role in the pleasurable reinforcing and psychomotor stimulant effects of amphetamines, the transmitters norepinephrine and serotonin also contribute substantially to these effects. Recent evidence suggests that the functional links that exist between norepinephrine and serotonin systems may be profoundly important in METH effects and dependence. However, these neurotransmitter systems have not been tested as extensively as targets of pharmacologic interventions. Thus, the purpose of this study is to examine whether the alpha-1-b antagonist prazosin blocks the self-reported effects, cognitive performance effects and cardiovascular effects of METH in a dose-related manner. Subsequent protocols will test the effect of the serotonin antagonist, cyproheptadine, and the combined norepinephrine/serotonin antagonist, quetiapine. Healthy, non-treatment-seeking METH users will be recruited. They will undergo extensive prestudy medical and psychiatric screening. Twelve volunteers (ages 18-50 years; 50% female; 10% Minority) who sign the informed consent will be recruited to complete the study on prazosin.

METH-abusing volunteers will undergo three sessions spaced 2 days apart. A single oral dose of prazosin (placebo, or 1mg, po) will be given in a randomized, double-blind design before METH or METH placebo administration in each session. METH will be given po in a dose (20 mg) that is well-tolerated by humans but that results in easily measurable effects by itself (Cruickshank and Dyer, 2009; Sevak et al, 2009; Parrot et al, 2011). Prior to and at several time points after prazosin/placebo,METH/placebo, or prazosin/METH administrations, self-report, cognitive performance and physiologic measures will be obtained.

The studies we propose are significant as they have the potential to identify treatment medications and elucidate new mechanisms of action and desirable characteristics for future medications development. Understanding the effects of treatment drugs in the context of concomitant METH use is an essential component of identifying potential pharmacotherapies for METH dependence that 1) alters the self-reported/performance effects 2) alters the cardiovascular effects and 3) alters the concentration-effect (pharmacodynamic) relationships of METH in human METH users. Using this broad pharmacologic approach to these human laboratory studies will provide insight into the appropriate combination of positive treatment effects with minimal side effects for the ultimate development of a successful treatment for METH abuse. The results should be generalizable to METH abusers and to the development of new treatments for METH abuse that will benefit all members of society. Understanding pharmacologic interactions will lessen complications of drug abuse and provide more rapid introduction of effective new treatments into medical practice.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Must be between the ages of 18-50 years (inclusive).
  • Must be a current METH user, with self-reported amount of IV use being greater than the total administered in the study.
  • Must have recent use confirmed by a urine toxicology screen positive for amphetamines.
  • Must not be seeking treatment for METH abuse/dependence.

Exclusion Criteria:

  • Ill health (major cardiovascular, renal, endocrine, hepatic disorder, to be determined by history provided by the prospective subject or laboratory evaluation as outlined below).
  • Current diagnosis of other drug or alcohol physical dependence (other than nicotine or caffeine).
  • History of major organic psychiatric disorder (psychosis, schizophrenia, bipolar, mania) or significant psychiatric symptoms at the time of evaluation for study participation, including suicidal ideation.
  • Pregnancy, plans to become pregnant, or fertile women without adequate means of contraception.
  • Present or recent use of over-the-counter or prescription psychoactive drug or drug that would have major interaction with drugs to be tested.
  • Liver function tests greater than three times normal, BUN and creatinine outside of normal range, or thyroid function tests outside of normal range.
  • EKG abnormalities including but not limited to: bradycardia (<60 bpm); prolonged QTc interval (>450 msec); Wolff-Parkinson-White syndrome; wide complex tachycardia; 2nd degree, Mobitz type II heart block; 3rd degree heart block; left or right bundle branch block.
  • Medical contraindication to or prior serious adverse effects from METH or stimulants (i.e., seizures, cardiac arrest) or medical contraindication to test agents (see risks section). Significant physical or psychiatric illness which might impair the ability to safely complete the study or that might be complicated by the study drugs, including prior seizures (after age 8) or other active neurological disease or clinically significant abnormalities on physical examination or screening laboratory values.
  • Current enrollment in a METH, alcohol, or other drug treatment program or current legal problems relating to METH, alcohol, or other drug use, including awaiting trial or supervision by a parole or probation officer.
  • Left ventricular ejection fraction < 40% as determined in the screening echocardiogram.
  • Body Mass Index >35 or <18.
  • Currently trying to quit METH use.
  • History of serious adverse event or hypersensitivity to METH or other study drugs
  • Currently taking any medication (including HAART for HIV) other than over-the-counter nonsteroidal anti-inflammatory medications, topical medications, inhaled asthma therapy, and over-the-counter nonsedating antihistamines.
  • Any other condition the PI or staff feels will put the subject at risk for entering the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01178138

Locations
United States, Arkansas
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
Sponsors and Collaborators
University of Arkansas
Investigators
Principal Investigator: William B Gentry, MD University of Arkansas
  More Information

No publications provided

Responsible Party: University of Arkansas
ClinicalTrials.gov Identifier: NCT01178138     History of Changes
Other Study ID Numbers: 110371, 1R01DA026916-01
Study First Received: August 4, 2010
Last Updated: July 3, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Arkansas:
substance abuse

Additional relevant MeSH terms:
Methamphetamine
Prazosin
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Central Nervous System Stimulants
Central Nervous System Agents
Therapeutic Uses
Adrenergic Agents
Adrenergic Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Dopamine Uptake Inhibitors
Antihypertensive Agents
Cardiovascular Agents
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists
Adrenergic Antagonists

ClinicalTrials.gov processed this record on July 20, 2014