Perindopril-Methamphetamine Interaction Study - Full Text View

Sponsor:	National Institute on Drug Abuse (NIDA)
Information provided by:	National Institute on Drug Abuse (NIDA)
ClinicalTrials.gov Identifier:	NCT00249665

Purpose

Due to its ease of synthesis and powerful psychostimulant effects, abuse of methamphetamine has increased rapidly over the last decade. No medications are currently approved for the treatment of methamphetamine dependence or withdrawal. The purpose of this study is to determine whether perindopril, an angiotensin converting enzyme (ACE) inhibitor, modifies cardiovascular responses and adverse events when taking methamphetamines.

Condition	Intervention	Phase
Methamphetamine Dependence Substance-Related Disorders	Drug: Perindopril Drug: Placebo Drug: perindopril	Phase I Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacokinetics/Dynamics Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Perindopril-Methamphetamine Interaction Study

Resource links provided by NLM:

MedlinePlus related topics: Drug Abuse Drug Reactions Methamphetamine

Drug Information available for: Methamphetamine hydrochloride Perindopril Perindopril erbumine Amphetamine Methamphetamine

U.S. FDA Resources

Further study details as provided by National Institute on Drug Abuse (NIDA):

Primary Outcome Measures:

Adverse events; measured throughout methamphetamine infusions and at Day 18 [ Time Frame: Inpt study phase and followup ] [ Designated as safety issue: Yes ]
Cardiovascular responses; measured throughout methamphetamine infusions and at Day 18 [ Time Frame: Inpt phase and followup ] [ Designated as safety issue: Yes ]
Reinforcing effects of methamphetamine; measured throughout methamphetamine infusions and at Day 18 [ Time Frame: day 1-18 ] [ Designated as safety issue: No ]

Enrollment:	30
Study Start Date:	August 2004
Study Completion Date:	January 2008
Primary Completion Date:	January 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Placebo Comparator: I Placebo	Drug: Perindopril 0mg to 16mg Drug: Placebo Capsule
Experimental: 2 perindopril 2mg	Drug: Perindopril 0mg to 16mg Drug: perindopril 2mg
Experimental: 3 perindopril 4mg	Drug: Perindopril 0mg to 16mg Drug: perindopril 4mg
Experimental: 4 perindopril 8mg	Drug: Perindopril 0mg to 16mg Drug: perindopril 8mg
Experimental: 5 perindopril 16mg	Drug: Perindopril 0mg to 16mg Drug: perindopril 16mg

Detailed Description:

Methamphetamine is a commonly abused drug associated with dopamine neurotoxicity. It damages brain cells that contain dopamine, which can result in Parkinson-like symptoms, such as muscle rigidity, tremors, and limited movement. Because ACE inhibitors have the potential to reverse methamphetamine's neurotoxicity effects, they may prove useful as treatment drugs. Perindopril is an antihypertensive medication that demonstrates greater activity in the central nervous system than other ACE inhibitors. The purpose of this study is to determine whether perindopril modifies cardiovascular responses and adverse events during methamphetamine administration. In addition, this study will determine whether perindopril alters methamphetamine pharmacokinetics and its reinforcing effects, thus making perindopril a possible treatment option.

Participants in this double-blind, placebo-controlled trial will initially receive baseline infusions of methamphetamine. Those that tolerate the baseline methamphetamine will be randomly assigned to receive either perindopril or placebo. Perindopril will be administered at a dose of either 2, 4, 8, or 16 mg per day over a 5-day inpatient period. On Days 3 and 5, participants will receive infusions of 15 and 30 mg of intravenous methamphetamine. Each methamphetamine infusion will be preceded or followed by an intravenous infusion of saline. Heart rate and electrocardiograms will be continuously monitored. Participants will be discharged 2 days after the final doses of methamphetamine and perindopril, and will return approximately 1 week later (Day 18) for an additional evaluation.

Eligibility

Ages Eligible for Study:	18 Years to 45 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Current and past history of methamphetamine use
Not currently seeking treatment for methamphetamine dependence
Meets DSM-IV criteria for methamphetamine abuse or dependence, as determined by the SCID
At least one positive urine test for methamphetamines within the 4 weeks prior to study entry
Speaks and writes English
Females must agree to use an adequate form of contraception for the duration of the study and have a negative pregnancy test prior to study entry

Exclusion Criteria:

History of an adverse medical reaction to methamphetamine or other psychostimulants, including loss of consciousness, chest pain, cardiac ischemia, or seizure
Current psychiatric disorder, other than drug abuse or dependence, including major depression, bipolar disorder, schizoaffective disorder, schizophrenia, organic brain disease, or dementia
Meets DSM-IV criteria for dependence on opiates, benzodiazepines, alcohol, or other sedative-hypnotics
Currently taking opiate-substitution therapy (e.g., methadone, LAAM, or buprenorphine) within the 2 months prior to study entry
Current or past history of a seizure disorder, including alcohol- or psychostimulant-related seizures, febrile seizures, or familial history of seizure disorders
Diagnosed with adult asthma, including a history of acute asthma within the 2 years prior to study entry
Diagnosed with chronic obstructive pulmonary disease within the 2 years prior to study entry
Treatment with an inhaled or oral beta-adrenergic agonist within the 2 years prior to study entry
Head trauma that resulted in neurological abnormalities (e.g., loss of memory for greater than 5 minutes or that required hospitalization)
Any unstable medical condition that might make participation unsafe, including AIDS, acute hepatitis, active tuberculosis, unstable cardiac disease, unstable diabetes, kidney or liver insufficiency (defined as serum bilirubin or creatine levels exceeding 1.5 times the normal limit)
Pregnant or breastfeeding
Current suicidal ideation, as determined by a SCID interview
Clinically significant electrocardiogram abnormalities
Donated blood within 4 weeks prior to study entry
Participated in another clinical trial within 4 weeks prior to study entry
Unable to complete study procedures due to incarceration or relocation from the area
Known or suspected hypersensitivity to perindopril, other ACE inhibitors, methamphetamine, or other psychostimulants
Currently using perindopril, potassium supplements, potassium-sparing diuretics, other antihypertensive medication, or any medications that may interact with study drugs

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00249665

Locations

United States, California
UCLA, Integrated Substance Abuse Programs
Los Angeles, California, United States, 90024

Sponsors and Collaborators

National Institute on Drug Abuse (NIDA)

Investigators

Principal Investigator:

Thomas Newton, M.D.

University of California, Los Angeles

More Information

No publications provided

Responsible Party:	Newton, Thomas F, UCLA
ClinicalTrials.gov Identifier:	NCT00249665 History of Changes
Other Study ID Numbers:	NIDA-17182-1, R21-17182-1, DPMC
Study First Received:	November 3, 2005
Last Updated:	July 9, 2008
Health Authority:	United States: Federal Government; United States: Food and Drug Administration

Additional relevant MeSH terms:

Substance-Related Disorders
Mental Disorders
Methamphetamine
Amphetamine
Perindopril
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
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Antihypertensive Agents
Cardiovascular Agents

ClinicalTrials.gov processed this record on February 09, 2012