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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bernard Le Foll, Centre for Addiction and Mental Health
ClinicalTrials.gov Identifier:
NCT01699828
First received: October 2, 2012
Last updated: June 3, 2014
Last verified: June 2014
  Purpose

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 Intervention Phase
Smoking Cessation
Tobacco Use Cessation
Drug: Buspirone
Drug: Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Exploring Occupancy of Dopamine D3 Receptor by Buspirone in Humans Using PET

Resource links provided by NLM:


Further study details as provided by Centre for Addiction and Mental Health:

Primary Outcome Measures:
  • Dose-response occupancy of buspirone at DRD3 [ Time Frame: few months ] [ Designated as safety issue: No ]
    [11C]-(+)-PHNO binding potential at three doses of buspirone and placebo.


Enrollment: 6
Study Start Date: October 2012
Study Completion Date: June 2014
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Buspirone 120 mg
Buspirone 120 mg (encapsulated).
Drug: Buspirone
The buspirone will be given once as a tablet and encapsulated for blinding.
Other Name: 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 Name: Buspar
Placebo Comparator: Placebo
Placebo (encapsulated)
Drug: Placebo
Placebo will be lactose and encapsulated for blinding. A single capsule will be given.
Other Name: 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 Name: Buspar

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.

  Eligibility

Ages Eligible for Study:   19 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01699828

Locations
Canada, Ontario
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
  More Information

Additional Information:
No publications provided

Responsible Party: Bernard Le Foll, PI, Centre for Addiction and Mental Health
ClinicalTrials.gov Identifier: NCT01699828     History of Changes
Other Study ID Numbers: 186/2011
Study First Received: October 2, 2012
Last Updated: June 3, 2014
Health Authority: Canada: Health Canada

Keywords provided by Centre for Addiction and Mental Health:
buspirone
smoking cessation
dopamine
PET imaging
[11C]-(+)-PHNO

Additional relevant MeSH terms:
Dopamine
Dopamine Agents
Buspirone
Cardiotonic Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Protective Agents
Anti-Anxiety Agents
Tranquilizing Agents
Central Nervous System Depressants
Central Nervous System Agents
Psychotropic Drugs
Serotonin Receptor Agonists
Serotonin Agents

ClinicalTrials.gov processed this record on September 16, 2014