The Effects of Prazosin on Dopamine in Healthy Humans: A PET Pilot Study

Phase 1

Completed

Conditions: Healthy

Interventions: Drug: Prazosin Hydrochloride

Registration Number: NCT01999530

Lead Sponsor: Centre for Addiction and Mental Health

Brief Summary: The purpose of this study is to find out whether short term treatment with a antihypertensive medication prazosin, can influence the levels of a dopamine in the brain. We will examine the levels of dopamine in the the brain using Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI). We hypothesize that there will be no significant changes in dopamine levels in healthy individuals taking prazosin.

Detailed Description: The purpose of this study is to find out whether short term treatment with a antihypertensive medication prazosin, can influence the levels of dopamine in the brain. We will examine the levels of dopamine in the the brain using Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI). The study will involve three PET scans and one MRI. One PET scan will be performed before the participants take prazosin for approximately three weeks, and the last two PET scans will be performed after the prazosin medication phase. We hypothesize that there will be no significant changes in dopamine levels in healthy individuals taking prazosin.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 20

Inclusion Criteria

Healthy males and females of any ethnic origin between 19 and 45 years old

Exclusion Criteria

Use of any illicit drugs in past 3 months prior to randomization and/or have a current or past diagnosis of drug abuse/dependence (including alcohol)
Current or past DSM-IV diagnosis of any Axis I psychiatric disorder
Major psychiatric illness and/or substance dependence in first order relatives
Current active or past suicidal ideation
Baseline systolic blood pressure outside the normal range
Current use of medications that could interact with prazosin (e.g. beta blockers, phosphodiesterasetype 5 inhibitors, indomethacin, verapamil, modafinil, clonidine)
Current use or use during the previous month of medication that may affect the CNS at the time of scanning (e.g. neuroleptics, bupropion)
Any significant abnormalities in baseline blood results (e.g. CBC, renal and hepatic indicators) or ECG readings that would preclude the use of prazosin
Pregnancy, trying to become pregnant or breastfeeding
Presence of metal objects in the body (e.g. some artificial joints, bone pins, surgical clips, skull plate, certain part of dental braces) or implanted electronic devices (e.g. cardiac pacemaker, neurostimulator), that preclude safe MR scanning
Claustrophobia
Participation in any nuclear medicine procedures that, including the dose received during participation in this study, will bring the total radiation dose over the currently approved guideline of 20mSv in a 12-month period
Cardiovascular or cerebrovascular diseases
History of or current neurological illnesses including seizure disorders, migraine, multiple sclerosis, movement disorders, head trauma, CVA or CNS tumor
Abnormal body mass (defined as not within 20% of normal BMI
Learning disability, amnesia or other conditions that impede memory and attention

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Prazosin Hydrochloride	Prazosin Hydrochloride	Gradual upward titration to 15mg/day (or highest dose tolerated) for approximately three weeks.

Primary Outcome Measures

Name	Time	Method
Changes in [11C]-(+)-PHNO Binding (Measured as Binding Potential) in Dorsal Caudate (DC)	3 weeks after taking prazosin	Binding potential (an estimate of the ratio of Bmax/kd) was measured by positron emission tomography to determine if taking prazosin alters the amount of tracer bound to receptors. A negative change in binding potential means a decrease in binding potential and a positive change in binding potential represents an increase. Bmax is the total density of receptors. kd is the affinity of a drug for the target

Secondary Outcome Measures