Healthy
Conditions
Keywords
prazosin, dopamine, healthy, Positron Emission Tomography, PHNO, scan, effect
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.
Interventions
Gradual upward titration to 15mg/day for approximately three weeks.
Sponsors
Ontario Lung Association
Pfizer
Centre for Addiction and Mental Health
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to 45 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Prazosin Hydrochloride Gradual upward titration to 15mg/day (or highest dose tolerated) for approximately three weeks.
Prazosin Hydrochloride: Gradual upward titration to 15mg/day for approximately three weeks. | 7 |
| Total | 7 |
Baseline characteristics
| Characteristic | Prazosin Hydrochloride |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants |
| Race/Ethnicity, Customized Asian | 1 participants |
| Race/Ethnicity, Customized Caucasian | 3 participants |
| Race/Ethnicity, Customized Hispanic | 2 participants |
| Race/Ethnicity, Customized Mixed | 1 participants |
| Region of Enrollment Canada | 7 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 6 / 20 |
| serious Total, serious adverse events | 0 / 20 |
Outcome results
Primary
Changes in [11C]-(+)-PHNO Binding (Measured as Binding Potential) in Dorsal Caudate (DC)
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
Time frame: 3 weeks after taking prazosin
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Prazosin Hydrochloride | Changes in [11C]-(+)-PHNO Binding (Measured as Binding Potential) in Dorsal Caudate (DC) | 2.1 binding potential |