Effects of Diacetylmorphine (DAM) on Brain Function and Stress Response
|ClinicalTrials.gov Identifier: NCT01174927|
Recruitment Status : Completed
First Posted : August 4, 2010
Last Update Posted : October 15, 2015
|Condition or disease||Intervention/treatment||Phase|
|Opiate||Drug: diacetylmorphine (DAM) Other: Placebo||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||60 participants|
|Intervention Model:||Crossover Assignment|
|Official Title:||The Effects of Diacetylmorphine (Heroin) on Human Brain Functions and Stress Response|
|Study Start Date :||March 2010|
|Primary Completion Date :||December 2010|
|Study Completion Date :||February 2012|
Active Comparator: Heroin-dependent patients_1
daily dose of diacetylmorphine (30 mg to 500 mg) in 5 ml
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 Name: heroin
Placebo Comparator: Heroin-dependent patients_2
5 ml saline
- brain functions [ Time Frame: 1 hour ]
- stress response [ Time Frame: pre and post stress measurements ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01174927
|Basel, Switzerland, 4025|
|Principal Investigator:||Marc Walter, MD||UPK, University Hospital Basel|