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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2010 by University Hospital, Basel, Switzerland.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
University of Bern
Information provided by:
University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier:
NCT01174927
First received: August 2, 2010
Last updated: August 3, 2010
Last verified: August 2010
  Purpose

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. Stress is a key factor for relapse in heroin-dependent patients. 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, especially in patients with HD and concomitant borderline personality disorder traits.

Specific aims: To investigate the effect of DAM 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 HD.

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.


Condition Intervention Phase
Diacetylmorphine
Drug Effects
Physiological Stress Response
Brain Function
Drug: diacetylmorphine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Subject)
Primary Purpose: Diagnostic
Official Title: The Effects of Diacetylmorphine (Heroin) on Human Brain Functions and Stress Response

Resource links provided by NLM:


Further study details as provided by University Hospital, Basel, Switzerland:

Primary Outcome Measures:
  • brain functions [ Time Frame: 1 hour ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • stress response [ Time Frame: pre and post stress measurements ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 30
Study Start Date: March 2010
Estimated Study Completion Date: February 2012
Estimated Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: diacetylmorphine, saline Drug: diacetylmorphine
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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • opioid dependence

Exclusion Criteria:

  • other psychiatric disorders
  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: NCT01174927

Locations
Switzerland
UPK Recruiting
Basel, Switzerland, 4025
Contact: Hana Gerber, MA    061 325 56 86    hana.gerber@upkbs.ch   
Principal Investigator: Marc Walter, MD         
Sub-Investigator: Hana Gerber, MA         
Sponsors and Collaborators
University Hospital, Basel, Switzerland
University of Bern
Investigators
Principal Investigator: Marc Walter, MD UPK, University Hospital Basel
  More Information

Additional Information:
No publications provided

Responsible Party: Universitätre Psychiatrische Kliniken UPK Basel: Switzerland
ClinicalTrials.gov Identifier: NCT01174927     History of Changes
Other Study ID Numbers: DAM2010_01, SNF127544
Study First Received: August 2, 2010
Last Updated: August 3, 2010
Health Authority: Switzerland: Swissmedic

Additional relevant MeSH terms:
Heroin
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 18, 2014