Exploring Occupancy of Dopamine D3 Receptor by Buspirone in Humans Using PET

Sponsor

Centre for Addiction and Mental Health (Other)

Overall Status

Completed

CT.gov ID

NCT01699828

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The objective of the present study is to use positron emission tomography brain imaging to investigate D3 occupancy of buspirone, an FDA-approved anxiolytic which acts as a serotonin partial agonist but has recently been identified as a D3 antagonist. It is hypothesized that clinically relevant doses of buspirone will occupy the D3 receptor.

Condition or Disease	Intervention/Treatment	Phase
Smoking Cessation Tobacco Use Cessation	Drug: Buspirone Drug: Placebo	Phase 1/Phase 2

Detailed Description

Buspirone is used for anxiety disorder treatment, a therapeutic effect that has been thought to be mediated through its partial agonist properties at the serotonin receptor. However, since one PET study in humans has shown low occupancy of the serotonin by buspirone in clinical doses and since the DRD3 has been recently implicated in anxiety, some therapeutic effects of buspirone may be mediated through the DRD3. In human clinical studies, promising effects of buspirone have been reported for treatment of substance dependence, including tobacco, marijuana, and opiates, and clinical studies in cocaine dependent subjects are underway. However, it is unclear if buspirone is producing those effects through the DRD3 and no human study has incorporated a PET imaging component to investigate this question; it remains unclear whether buspirone significantly occupies the DRD3 at therapeutic doses in humans.

Study Design

Study Type:

Interventional

Actual Enrollment :

6 participants

Allocation:

Non-Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

Exploring Occupancy of Dopamine D3 Receptor by Buspirone in Humans Using PET

Study Start Date :

Oct 1, 2012

Actual Primary Completion Date :

Jun 1, 2014

Actual Study Completion Date :

Jun 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Buspirone 120 mg Buspirone 120 mg (encapsulated).	Drug: Buspirone The buspirone will be given once as a tablet and encapsulated for blinding. Other Names: Buspar
Experimental: Buspirone 60 mg Buspirone 60 mg (encapsulated)	Drug: Buspirone The buspirone will be given once as a tablet and encapsulated for blinding. Other Names: Buspar
Placebo Comparator: Placebo Placebo (encapsulated)	Drug: Placebo Placebo will be lactose and encapsulated for blinding. A single capsule will be given. Other Names: lactose
Experimental: Buspirone 30 mg Buspirone 30 mg (encapsulated).	Drug: Buspirone The buspirone will be given once as a tablet and encapsulated for blinding. Other Names: Buspar

Outcome Measures

Primary Outcome Measures

Dose-response occupancy of buspirone at DRD3 [few months]
[11C]-(+)-PHNO binding potential at three doses of buspirone and placebo.

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

19 years or older

Exclusion Criteria:

Medical condition including cardiovascular, renal, hepatic or cerebrovascular diseases
History of or current neurological illnesses including seizure disorders, migraine, multiple sclerosis, movement disorders, head trauma, CVA or CNS tumor, - Present or past psychiatric condition including mood, anxiety, psychotic disorders and substance abuse and/or dependence.
Condition that precludes use of buspirone or that will interfere with participation in the present study (such as hypersensitive to buspirone hydrochloride).
Pregnancy or breastfeeding.
Presence of metal objects in the body or implanted electronic devices, that preclude safe MR scanning.
Claustrophobia.
Current use or use during the previous month of medication that may affect the CNS, including monoamine oxidase inhibitor (MAOI) or positive during drug screening for drugs of abuse or any medication that could increase the risk of buspirone administration.
Exposure to radiation in the last 12 month exceeding permissible limit for subjects participating in research.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Center for Addiction and Mental Health	Toronto	Ontario	Canada	M5S 2S1

Sponsors and Collaborators

Centre for Addiction and Mental Health

Investigators

Principal Investigator: Isabelle Boileau, PhD, Center for Addiction and Mental Health
Principal Investigator: Bernard Le Foll, MD, PhD, Center for Addiction and Mental Health