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

• Sponsor: Centre for Addiction and Mental Health (Other)
• Overall Status: Completed
• CT.gov ID: NCT01999530
• Collaborator: Ontario Lung Association (Other), Pfizer (Industry)
• Enrollment: 20
• Location: 1
• Arm: 1
• Actual Duration (Months): 33
• Patients Per Site Per Month: 0.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Prazosin Hydrochloride	Phase 1

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Exploring the Effects of Prazosin on Basal Dopamine in Healthy Humans: A [11C]-(+)-PHNO PET Pilot Study
• Actual Study Start Date: Nov 1, 2013
• Actual Primary Completion Date: Aug 1, 2016
• Actual Study Completion Date: Aug 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Prazosin Hydrochloride Gradual upward titration to 15mg/day (or highest dose tolerated) for approximately three weeks.	Drug: Prazosin Hydrochloride; Gradual upward titration to 15mg/day for approximately three weeks.; Other Names: Teva-Prazosin Prazosin Minipress

Outcome Measures

Primary Outcome Measures

1. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Centre for Addiction and Mental Health	Toronto	Ontario	Canada	M5T 1R8

Sponsors and Collaborators

• Centre for Addiction and Mental Health
• Ontario Lung Association
• Pfizer

Investigators

• Principal Investigator: Bernard Le Foll, MD, PhD, Centre for Addiction and Mental Health

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Information about research at the Centre for Addiction and Mental Health, Canada's largest mental health and addiction teaching

Publications

None provided.

• Responsible Party: Bernard Le Foll, Principal Investigator, Centre for Addiction and Mental Health
• ClinicalTrials.gov Identifier: NCT01999530
• Other Study ID Numbers: 224/2012
• First Posted: Dec 3, 2013
• Last Update Posted: May 30, 2019
• Last Verified: May 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Bernard Le Foll, Principal Investigator, Centre for Addiction and Mental Health: prazosin; dopamine; healthy; Positron Emission Tomography; PHNO; scan; effect
• Additional relevant MeSH terms: Prazosin

Study Results

Participant Flow

Arm/Group Title	Prazosin Hydrochloride
Arm/Group Description	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.
Period Title: Overall Study
STARTED	20
COMPLETED	7
NOT COMPLETED	13

Baseline Characteristics

Arm/Group Title	Prazosin Hydrochloride
Arm/Group Description	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.
Overall Participants	7
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	7 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	7 100%
Race/Ethnicity, Customized (participants) [Number]
Asian	1 14.3%
Caucasian	3 42.9%
Hispanic	2 28.6%
Mixed	1 14.3%
Region of Enrollment (participants) [Number]
Canada	7 100%

Outcome Measures

1. Primary Outcome

Title	Changes in [11C]-(+)-PHNO Binding (Measured as Binding Potential) in Dorsal Caudate (DC)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Prazosin Hydrochloride
Arm/Group Description	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.
Measure Participants	7
Mean (Full Range) [binding potential]	2.1

Adverse Events

Arm/Group Title	Prazosin Hydrochloride
Arm/Group Description	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.
All Cause Mortality
	Prazosin Hydrochloride
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Prazosin Hydrochloride
	Affected / at Risk (%)	# Events
Total	0/20 (0%)
Other (Not Including Serious) Adverse Events
	Prazosin Hydrochloride
	Affected / at Risk (%)	# Events
Total	6/20 (30%)
Gastrointestinal disorders
Nausea	6/20 (30%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.