Perindopril-Methamphetamine Interaction Study

Substance-Related Disorders Clinical Trial

Official title:

Perindopril-Methamphetamine Interaction Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00249665
• Other study ID #: NIDA-17182-1
• Secondary ID: R21-17182-1DPMC
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: November 3, 2005
• Last updated: July 9, 2008
• Start date: August 2004
• Est. completion date: January 2008

Study information

• Verified date: July 2008
• Source: National Institute on Drug Abuse (NIDA)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: January 2008
• Est. primary completion date: January 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 45 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Methamphetamine Dependence
• Substance-Related Disorders

Intervention

Drug:
• Perindopril
0mg to 16mg
• Placebo
Capsule
• perindopril
2mg
• perindopril
4mg
• perindopril
8mg
• perindopril
16mg

Locations

Country	Name	City	State
United States	UCLA, Integrated Substance Abuse Programs	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
National Institute on Drug Abuse (NIDA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse events; measured throughout methamphetamine infusions and at Day 18		Inpt study phase and followup	Yes
Primary	Cardiovascular responses; measured throughout methamphetamine infusions and at Day 18		Inpt phase and followup	Yes
Primary	Reinforcing effects of methamphetamine; measured throughout methamphetamine infusions and at Day 18		day 1-18	No