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

Substance-Related Disorders Clinical Trial

Official title:

Effects of Corticorelin Administration on Dopamine Transmission, Craving, and Mood in Cocaine Dependence: A [11C]-(+)-PHNO PET Investigation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01984177
• Other study ID #: 010/2012
• Status: Completed
• Phase: N/A
• First received: October 9, 2013
• Last updated: August 8, 2016
• Start date: June 2013
• Est. completion date: June 2016

Study information

• Verified date: August 2016
• Source: Centre for Addiction and Mental Health
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: June 2016
• Est. primary completion date: June 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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

Observational Model: Case Control, Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Behavior, Addictive
• Cocaine Addiction
• Cocaine-Related Disorders
• Disease
• Substance-Related Disorders

Intervention

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. Primary outcome measure ([11C]-(+)-PHNO) as well as Secondary outcome measures (self reported feeling, hormones and physiological measures) will be obtained before saline or Corticorelin/saline injection and for 90-120 minutes following injection.

Locations

Country	Name	City	State
Canada	Centre for Addiction and Mental Health	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Centre for Addiction and Mental Health

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PET measure: [11C]-(+)-PHNO binding	[11C]-(+)-PHNO binding on two occasions (following corticorelin and saline)	within a month following enrollment	No
Secondary	stress hormone levels	plasma cortisol, ACTH	in conjunction with PET	No
Secondary	subjective measures	subjective stress, craving, mood, drug effects	in conjunction with PET	No
Secondary	vital signs	heart rate, blood pressure	in conjunction with PET	Yes
Secondary	neuropsychological battery	battery of neuropsychological tasks to assess cognitive function, general intelligence, and personality.	once following PET	No

External Links

•   Information about research at the Centre for Addiction and Mental Health, Canada's largest mental health and addiction teaching hospital. It is fully affiliated with the University of Toronto, and is a PAHO/WHO Collaborating Centre