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

NCT ID: NCT01174927

Last Updated: 2015-10-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-03-31
• Study Completion Date: 2012-02-29

Brief 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.

Detailed 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.

Conditions

Opiate

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Heroin-dependent patients_1

daily dose of diacetylmorphine (30 mg to 500 mg) in 5 ml

Group Type: ACTIVE_COMPARATOR

diacetylmorphine (DAM)

Intervention Type: DRUG

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.

Heroin-dependent patients_2

5 ml saline

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Saline

Interventions

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.

Intervention Type: DRUG

Placebo

Saline

Intervention Type: OTHER

Other Intervention Names

heroin

Eligibility Criteria

Inclusion Criteria

• opioid dependence

Exclusion Criteria

• other psychiatric disorders

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Bern

OTHER

Sponsor Role: collaborator

University Hospital, Basel, Switzerland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marc Walter, MD

Role: PRINCIPAL_INVESTIGATOR

UPK, University Hospital Basel

Locations

UPK

Basel, Basel, Switzerland

Countries

Switzerland

Related Links

http://www.upkbs.ch

clinic homepage

Other Identifiers

SNF127544

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

DAM2010_01

Identifier Type: -

Identifier Source: org_study_id