Effects of Corticorelin Administration on Dopamine Transmission, Craving, and Mood in Cocaine Dependence

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Centre for Addiction and Mental Health
Sponsor:
Information provided by (Responsible Party):
Isabelle Boileau, Centre for Addiction and Mental Health
ClinicalTrials.gov Identifier:
NCT01984177
First received: October 9, 2013
Last updated: May 16, 2014
Last verified: May 2014
  Purpose

This study will, in a sample of cocaine-dependent and healthy control subjects, administer corticorelin and compare dopamine release between groups. Dopamine release will be measured using PET neuroimaging with the radiotracer [11C]-(+)-PHNO.


Condition Intervention
Cocaine-Related Disorders
Cocaine Addiction
Substance-Related Disorders
Drug: Corticotropin-Releasing Hormone

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Cross-Sectional
Official Title: Effects of Corticorelin Administration on Dopamine Transmission, Craving, and Mood in Cocaine Dependence: A [11C]-(+)-PHNO PET Investigation

Resource links provided by NLM:


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

Primary Outcome Measures:
  • PET measure: [11C]-(+)-PHNO binding [ Time Frame: within a month following enrollment ] [ Designated as safety issue: No ]
    [11C]-(+)-PHNO binding on two occasions (following corticorelin and saline)


Secondary Outcome Measures:
  • stress hormone levels [ Time Frame: in conjunction with PET ] [ Designated as safety issue: No ]
    plasma cortisol, ACTH

  • subjective measures [ Time Frame: in conjunction with PET ] [ Designated as safety issue: No ]
    subjective stress, craving, mood, drug effects

  • vital signs [ Time Frame: in conjunction with PET ] [ Designated as safety issue: Yes ]
    heart rate, blood pressure

  • neuropsychological battery [ Time Frame: once following PET ] [ Designated as safety issue: No ]
    battery of neuropsychological tasks to assess cognitive function, general intelligence, and personality.


Biospecimen Retention:   Samples With DNA

whole blood


Estimated Enrollment: 40
Study Start Date: July 2013
Estimated Study Completion Date: July 2017
Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
cocaine-dependent (CD)
cocaine-dependent individuals
Drug: Corticotropin-Releasing Hormone
Each subject will receive a single dose of Corticotropin-Releasing Hormone corticorelin on a single occasion, and a volume-matched saline injection on a second occasion. Corticorelin will be administered as an intravenous infusion over a 30- to 60-second interval at a dose of 1 ug/kg body weight. ~15 minutes after Corticorelin/saline injection, [11C]-(+)-PHNO will be administered followed by 90 minutes of PET scanning.
Other Name: corticorelin
healthy control (HC)
healthy age and sex-matched individuals who do not use cocaine
Drug: Corticotropin-Releasing Hormone
Each subject will receive a single dose of Corticotropin-Releasing Hormone corticorelin on a single occasion, and a volume-matched saline injection on a second occasion. Corticorelin will be administered as an intravenous infusion over a 30- to 60-second interval at a dose of 1 ug/kg body weight. ~15 minutes after Corticorelin/saline injection, [11C]-(+)-PHNO will be administered followed by 90 minutes of PET scanning.
Other Name: corticorelin

Detailed Description:

SCIENTIFIC SUMMARY The project will, in a sample of cocaine-dependent (CD) and healthy control (HC) subjects, use administration of Corticorelin, a synthetic form of corticotropin releasing factor (CRF)and PET imaging to assess dopamine (DA) transmission in addiction. We will use [11C]-(+)-PHNO PET to measure striatal DA receptor binding on two occasions: 1) following corticorelin administration and 2) following saline. The change in receptor binding between the two occasions (i.e., displacement of [11C]-(+)-PHNO by endogenous DA) will index DA release.

SUBJECTS CD subjects will meet DSM-IV criteria for abuse or dependence and be ~10d cocaine abstinent at the time of PET. HC will be recruited to match CD on age, sex, education, and cigarette smoking.

PRIMARY OUTCOME MEASURES We will measure [11C]-(+)-PHNO binding on two occasions (corticorelin, saline), with the difference between conditions indexing dopamine release; this measure will then be compared between cocaine-dependent and control subjects. We will also measure plasma cortisol and ACTH), physiological measures, and subjective craving and mood.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

CD subjects are recruited from the local community using flyers and internet advertisements, and through referral from local clinical programs. CD subjects are recruited from the community using flyers and internet advertisements.

Criteria

Inclusion Criteria:

  • Sign and date informed consent
  • Willing and able to complete trial as described in the protocol
  • Psychiatrically healthy (as per diagnostic interview) except for cocaine dependence in cocaine users and nicotine dependence in both groups
  • Mentally healthy
  • Medically healthy (as per medical exam) with no current use of medications that may interfere with hormone activity or psychological measurements

Exclusion Criteria:

  • Axis I psychiatric disorder (as per diagnostic interview), or medical condition that might interfere with participation in the study (as per medical exam)
  • Exposure to radiation in the last 12 months exceeding the amount permissible by the CAMH PET centre
  • Have received synthetic glucocorticoid or exogenous steroid therapy within one month of testing
  • Exceed normal body weight
  • If female: pregnancy or breast-feeding
  • Metal implants or paramagnetic objects contained within the body
  • Claustrophobia
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01984177

Contacts
Contact: Doris Payer, PhD 416.535.8501 ext 36280 doris.payer@camh.ca
Contact: Isabelle Boileau, PhD 416.535.8501 ext 34918 isabelle.boileau@camh.ca

Locations
Canada, Ontario
Centre for Addiction and Mental Health Recruiting
Toronto, Ontario, Canada, M5T 1R8
Principal Investigator: Isabelle Boileau, PhD         
Sub-Investigator: Doris Payer, PhD         
Sub-Investigator: Tony George, MD         
Sponsors and Collaborators
Centre for Addiction and Mental Health
Investigators
Principal Investigator: Isabelle Boileau, PhD Centre for Addiction and Mental Health, Research Imaging Centre
  More Information

Additional Information:
No publications provided

Responsible Party: Isabelle Boileau, Clinical Research Scientist, Centre for Addiction and Mental Health
ClinicalTrials.gov Identifier: NCT01984177     History of Changes
Other Study ID Numbers: 010/2012
Study First Received: October 9, 2013
Last Updated: May 16, 2014
Health Authority: Canada: Health Canada

Keywords provided by Centre for Addiction and Mental Health:
Substance-Related Disorders
Cocaine
Drug Addiction
Substance Addiction
Dopamine
Receptors, Dopamine D2
Receptors, Dopamine D3
Stress, Psychological
Corticorelin
Neuroendocrine System
Cortisol
Adrenocorticotropic Hormone
Positron-Emission Tomography
11C-PHNO

Additional relevant MeSH terms:
Substance-Related Disorders
Disease
Behavior, Addictive
Cocaine-Related Disorders
Pathologic Processes
Compulsive Behavior
Impulsive Behavior
Chemically-Induced Disorders
Mental Disorders
Hormones
Adrenocorticotropic Hormone
Corticotropin-Releasing Hormone
Cocaine
Dopamine
Dopamine Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Vasoconstrictor Agents
Cardiovascular Agents
Dopamine Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014