Effects of Diacetylmorphine (DAM) on Brain Function and Stress Response

Opiate Clinical Trial

Official title:

The Effects of Diacetylmorphine (Heroin) on Human Brain Functions and Stress Response

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01174927
• Other study ID #: DAM2010_01
• Secondary ID: SNF127544
• Status: Completed
• Phase: Phase 1
• First received: August 2, 2010
• Last updated: October 13, 2015
• Start date: March 2010
• Est. completion date: February 2012

Study information

• Verified date: October 2015
• Source: University Hospital, Basel, Switzerland
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: Swissmedic
• Study type: Interventional

Clinical Trial Summary

The aims of the study are to investigate the effects of diacetylmorphin (heroin) on brain using functional magnetic resonance imaging (fMRI), coupled with measurements of cortisol concentrations and neurophysiological stress parameters during the presentation of emotional and cognitive stimuli in patients with heroin dependence.

Description:

Background: Heroin dependence (HD) is a chronic relapsing brain disorder that is defined by a compulsion to seek and use heroin, and a loss of control in limiting intake.

The prescription of diacetylmorphine (heroin) itself for maintenance has become an established treatment in several European countries. However, the neurobiological effects of diacetylmorphine (DAM) on brain function and stress response have not been studied so far. Imaging the acute effects of DAM administration during stress stimuli would elucidate the neurocircuitry and neurobiology of substance use in patients with HD.

Working hypothesis: The investigators expect that DAM attenuates the engagement of brain regions involved in response inhibition (prefrontal and anterior cingulate cortex), emotional processing (amygdala) and working memory (frontal and mediotemporal cortex). Additionally, we hypothesize that DAM reduces stress response (cortisol, heart rate, skin conductance) to emotional and cognitive stimuli.

Methods: Thirty heroin-dependent patients on stable heroin maintenance will be examined in a randomized placebo-controlled crossover design. They will be compared with 30 heroin-dependent age- and gender-matched but otherwise healthy volunteers receiving saline. The heroin-dependent patients will administer either their individual dose of prescribed DAM dose or saline through an indwelling intravenous line. Afterwards they will complete four experimental paradigms testing response inhibition, emotional processing and working memory while brain responses are measured with fMRI. Before and after the fMRI investigation cortisol samples, DAM blood levels, neurophysiological and psychological stress parameters, such as skin conductance, heart rate, anxiety, anger, and heroin craving will be measured.

Expected value of the proposed project: DAM effects on brain function and stress will advance our understanding of the mechanisms underlying HD. It is the first neuroimaging study investigating the neural basis of HD after intravenous DAM administration in humans.

Determining the neurofunctional and neurophysiological basis of heroin dependence may facilitate clinical diagnosis and improve clinical interventions such as prevention and treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: February 2012
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• opioid dependence

Exclusion Criteria:

• other psychiatric disorders

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Opiate

Intervention

Drug:
• diacetylmorphine (DAM)
The heroin-dependent patients will administer either their individual dose of prescribed DAM dose or placebo (saline) through an indwelling intravenous line. Afterwards they will complete four experimental paradigms testing response inhibition, emotional processing and working memory while brain responses are measured with fMRI. Before and after the fMRI investigation cortisol samples, DAM blood levels, neurophysiological and psychological stress parameters, such as skin conductance, heart rate, anxiety, anger, and heroin craving will be measured.

Other:
• Placebo
Saline

Locations

Country	Name	City	State
Switzerland	UPK	Basel

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland	University of Bern

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	brain functions		1 hour	Yes
Secondary	stress response		pre and post stress measurements	Yes

External Links

•   clinic homepage