Working… Menu

An ACE Inhibitor (Perindopril) or an Angiotensin Receptor Blocker (Candesartan) as a Treatment for Methamphetamine Dependence

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01062451
Recruitment Status : Unknown
Verified July 2017 by Thomas Newton, Baylor College of Medicine.
Recruitment status was:  Active, not recruiting
First Posted : February 4, 2010
Last Update Posted : July 12, 2017
National Institute on Drug Abuse (NIDA)
Information provided by (Responsible Party):
Thomas Newton, Baylor College of Medicine

Brief Summary:
The primary objective is to determine the dose dependent effects of treatment with perindopril on methamphetamine (MA)-induced craving and on the reinforcing effects of MA indexed by MA self-administration. We will also determine the effects of treatment with candesartan on MA-induced craving and on the reinforcing effects of MA indexed by MA self-administration.

Condition or disease Intervention/treatment Phase
Methamphetamine Dependence Methamphetamine Abuse Substance Abuse Drug: Perindopril Drug: Placebo Drug: Candesartan Phase 1

Detailed Description:
Our preliminary data indicate that the ACE inhibitor perindopril can attenuate MA-induced drug craving, suggesting that perindopril should be evaluated as a treatment for MA dependence. Candesartan works similarly to perindopril but should lack the U-shaped dose response. Like perindopril, candesartan is used for hypertension. Whereas perindopril reduces the synthesis of angiotensin II, candesartan blocks angiotensin II receptors.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Other
Official Title: An ACE Inhibitor or an Angiotensin Receptor Blocker as a Treatment for Methamphetamine Dependence
Study Start Date : May 2009
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Methamphetamine

Arm Intervention/treatment
Placebo Comparator: Placebo Drug: Placebo
Placebo treatment daily.
Other Name: Sugar pill

Active Comparator: Perindopril Drug: Perindopril
8 mg taken orally from days 0 through 7.
Other Name: Aceon

Active Comparator: Candesartan Drug: Candesartan
16 mg taken orally from days 0 through 7.
Other Name: Atacand

Primary Outcome Measures :
  1. The dose-dependent effects of an ace inhibitor or an angiotensin receptor blocker on MA- and cue-induced craving and on the reinforcing effects of MA indexed by MA self-administration. [ Time Frame: 7 days ]
    Participants demonstrating MA-induced craving will then be randomized to active study medication (perindopril or candesartan) or matched placebo (day 0). Over days 4 to 7 a variety of procedures will be completed to assess effects of MA and cue-induced craving. On day 7, reinforcing effects will be assessed will be assessed using self-administration procedures.

Secondary Outcome Measures :
  1. The effects of an ace inhibitor or an angiotensin receptor blocker on subjective measures. [ Time Frame: 7 days ]
    On days 3 and 5, participants will receive sample doses of 15mg or 30mg MA paired with a dose of placebo saline separated by 180 min, with the order of administration randomized. Subjective effects of MA will be assessed using visual analogue scales (VAS).

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Be English-speaking non-treatment-seeking volunteers.
  • Be between 18-55 years of age.
  • Meet DSM-IV TR criteria for MA dependence.
  • Have a self-reported history of using MA by the IV route.
  • Have vital signs as follows: resting pulse between 50 and 90 bpm, blood pressures between 85-150mm Hg systolic and 45-90mm Hg diastolic.
  • Have a breathalyzer test indicating an undetectable blood alcohol level upon 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 ECG that demonstrates normal sinus rhythm, normal conduction, 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 and the principal investigator. Adult ADHD is allowable, as long as symptoms do not interfere with participation.
  • Demonstrate MA-induced craving, evidenced by a change in "desire" greater than 20 on a 0 to 100mm VAS.
  • Weigh between 60 and 100kg.

Exclusion Criteria:

  • Have any previous medically adverse reaction to MA, including loss of consciousness, chest pain, or epileptic seizure.
  • Have neurological or psychiatric disorders, such as: episode of major depression within the past 2 years as assessed by MINI; lifetime history of schizophrenia, other psychotic illness, or bipolar illness as assessed by MINI; current organic brain disease or dementia assessed by clinical interview; history of or any current psychiatric disorder which would require ongoing treatment or which would make study compliance difficult; history of suicide attempts within the past three months and/or current suicidal ideation/plan; history of psychosis occurring in the absence of current MA use.
  • Meet DSM-IV criteria for abuse or dependence on alcohol or other drugs, except for nicotine or marijuana.
  • Have evidence of clinically significant heart disease or hypertension, 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, and weekly throughout the study.
  • Have any history of asthma, chronic coughing and wheezing, or other chronic respiratory illnesses.
  • Currently use alpha or beta agonists, theophylline, or other sympathomimetics.
  • Have any other illness, condition, or use of medications, which in the opinion of the P.I. and/or the admitting physician would preclude safe and/or successful completion of the study.

Rationale for Other Exclusion Criteria:

Participants with asthma or who take medications for asthma are excluded due to potential adverse interactions between treatment medications and MA. Participants who use alcohol heavily are excluded due to the potential of withdrawal symptoms in the hospital. Participants with active HIV disease are excluded to avoid potentially exacerbating their underlying illness and because of potential drug interactions. Reliable methods of birth are required to prevent pregnancy, and the use of frequent urine pregnancy tests will exclude women who become pregnant. This is important because perindopril can produce significant birth defects.

Criteria for Discontinuation Following Initiation:

Participants will be discharged if they have a positive breath test indicating use of alcohol or a urine test indicating use of illicit use of drugs while on the study, if they do not comply with study procedures, or if they do not tolerate MA.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01062451

Layout table for location information
United States, Texas
Michael E. DeBakey VA Medical Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Baylor College of Medicine
National Institute on Drug Abuse (NIDA)
Layout table for investigator information
Principal Investigator: Thomas F Newton, M.D. Baylor College of Medicine
Layout table for additonal information
Responsible Party: Thomas Newton, Professor, Baylor College of Medicine Identifier: NCT01062451    
Obsolete Identifiers: NCT00249665
Other Study ID Numbers: H-23235
R01DA023468 ( U.S. NIH Grant/Contract )
DPMC ( Other Identifier: NIDA )
First Posted: February 4, 2010    Key Record Dates
Last Update Posted: July 12, 2017
Last Verified: July 2017
Keywords provided by Thomas Newton, Baylor College of Medicine:
Angiotensin receptor blocker
ACE Inhibitor
Additional relevant MeSH terms:
Layout table for MeSH terms
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors