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

Completed

• Conditions: Cocaine-Related Disorders; Cocaine Addiction; Substance-Related Disorders
• Interventions: Drug: Corticotropin-Releasing Hormone

• Registration Number: NCT01984177
• Lead Sponsor: Centre for Addiction and Mental Health

Brief Summary

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.

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.

Study Timeline

• Study Start: 2013-06
• Study First Submitted: 2013-10-09
• Study First Submitted QC: 2013-11-07
• Study First Posted: 2013-11-14
• Primary Completion: 2016-06
• Study Completion: 2016-06
• Status Verified: 2016-08
• Last Update Submitted: 2016-08-08
• Last Update Posted: 2016-08-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 17

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
cocaine-dependent (CD)	Corticotropin-Releasing Hormone	cocaine-dependent individuals
healthy control (HC)	Corticotropin-Releasing Hormone	healthy age and sex-matched individuals who do not use cocaine

Primary Outcome Measures

Name	Time	Method
PET measure: [11C]-(+)-PHNO binding	within a month following enrollment	\[11C\]-(+)-PHNO binding on two occasions (following corticorelin and saline)

Secondary Outcome Measures

Name	Time	Method
vital signs	in conjunction with PET	heart rate, blood pressure
stress hormone levels	in conjunction with PET	plasma cortisol, ACTH
subjective measures	in conjunction with PET	subjective stress, craving, mood, drug effects
neuropsychological battery	once following PET	battery of neuropsychological tasks to assess cognitive function, general intelligence, and personality.

Trial Locations

Locations (1)

Centre for Addiction and Mental Health; 🇨🇦 Toronto, Ontario, Canada