Trial document





This trial has been registered retrospectively.
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  DRKS00009253

Trial Description

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Title

The influence of oxytocin on alcohol craving in social drinkers during exposure to alcohol related cues

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Trial Acronym

BOxy

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URL of the Trial

http://not existing

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Brief Summary in Lay Language

In earier times the hormone oxytcin was well known in gynecology.During nativity it stimulates contractions and after nativity it stumulates the contractions of the breast glands.
The sucking of the infant on the papilla of the breast stimulates production an liberation of oxytocin in the brain. Oxytcoin itself stimulates the liberation of milk out of the breast glands.
Besindes these functions, oxytocin can also influence behavior. It enhances the binding between mother and infant.
The high oxytocin plasma level during breast feeding clam the mother and her cortisol plasma level. The infant also discharge oxytocin during bearst feeding and gets calm.
In the past years lots of studies could show that oxytocin influences interpersonal relationships in general. Recent studies could show that oxytocin enhances interpersonal relationship, the trust to other people and the emotional competence. It reduces stress and anxiety. It is not only produced during beast feend but also petting and the sexual act.

Several studies investgate role of oxytocin in psychiatric disorders. They investigate the role of oxytocin in anxiety disorders, borderline personality disorders, shizophrenia and autism.
The results of these studies were very heterogeneous.
The most impressive results were found in studies on patients suffering from autism. Caused by their illness these patients have problems with interpersonal relationships and in recognizing emotions of others. Besides this they show stereotype movements.
All these studies use an intranasal application of oxytocin so oxytocin can reach the brain directly. Recent stdies on alcohol dependent patients could show that intranasal oxytocin reduces withdrawl symptoms during detoxification. So that the patients need less medication during detoxification.
These results suggest that oxytocin also influences the pathophysiological processes in alcohol use disorders.
In alcohol dependent patients craving often is induced by confrontation with alcohol associated cues. Alcohol craving is one of the most important factors which induce relapses.
The aim of of the present study is to investigate the influence of oxytocin on alcohol craving in male social drinkers. This should help to find out, if an intranal application of oxytocin has relapse prevention effects in alcohol dependent patients and if it can be used during detoxifiaction treatment and follow up care.
Up to now the use of oxytocin for this group of patients is an of lable use in Germany and other European countries. .

In our study we investigate alcohol craving in two fMRI (two different measuring days).
At one measuring day the participants receive 24 IE oxytocin intranasal before going into the scanner. At the second measuring day the particiapnts get an intranasal placebo medication.
After receiving the intranasal medication the fMRI take place at both measuring days (Duration: 35 minutes). The fMRI take place in the labs of the Central Institue for Mental Health in Mannheim.

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Brief Summary in Scientific Language

Recently the central oxytocin system was studied concering its role in reproduction processes. In the last years research focussed on the role of oxytoin in social cognitions, emotions, stress, motoric processes (Meyer-Lindenberg, Domes, Kirsch, & Heinrichs, 2011).
Oxytocin is produced in the neurons of the
Nc. paraventricularis and suprachiasmaticus of the hypothalamus, which project to the hypophyse. Via this way oxytocin comes into the systemic circulation. Additionally, the neurons of the Nc. paraventricularis project to the limbic system and the midbrain where it works as a neurotransmitter and a neuromodulator (Knobloch et al., 2012).
In human research oxytocin is applicated via an intranasal application, which is a very effective stimulation method of the central oxytocin system (Born et al., 2002).

In humans the application of 16-24 IU oxytocin leads to an tenfold increase of oxytoin plasma levels for at least 7 hours (van Ijzendoorn, Bhandari, van der Veen, Grewen, & Bakermans-Kranenburg, 2012). After an intranasal application oxytocin reaches the central receptors via 5 different ways: via the systemic pathway after resorption through the olfactoric epithel, over the mucosic epithel of the mouth, via the cerebrospinal fluid after resorption through the bulbus olfactorius, over the Nervus trigeminus and paravascular spaces, which were connected with the interstitielle spaces in the brain (Guastella et al., 2013).
Studies using this method could show an increase of interpersonal trust (Kosfeld, Heinrichs, Zak, Fischbacher, & Fehr, 2005), the reduction of stress anxiety reactions especially under social supporting conditions(Heinrichs, Baumgartner, Kirschbaum & Ehlert, 2003). Additionally, they found an increase of positive interactions in conflicts between mates (Ditzen et al., 2009). Focussing on the neurobiology you find a reduced activity of the amygdala in the fMRI (Kirsch et al., 2005) and an increased connectivity between the Amygdala and the mesolimbic reward system, the orbitofrontal cortex and the caudal anterior cingulum (Berridge & Kringelbach, 2008).
Precilinal and clinical studies could show that oxytocin modifies the effect of alcohol to the organism. Preclinical studies could show an effect of oxytocin to the acute effects of alcohol.
A peripher or central administration of oxytocin blocks the develpment of tolerance to the muscle relaxant effects, the akinetic and hypnotic effects of alcohol in the mouse modell(Jodogne, Tirelli, Klingbiel & Legros, 1991).
Oxytocin knock out mice show a faster development of tolerance towards these effects of alcohol (Vadlamudi, Pedersen, Amico, Breese, & Knapp, 2004).
Additionally, Pedersen et al (2013) found that intranasal oxytocin (24 IU 2x/day) reduces withdrwal symptoms in alcohol dependent patients during an acute detoxyfication.
Probably Oxytocin could influence alcohol craving in alcohol dependent patients via the increased functional connectivity between the amygdala and the mesolimbic reward system. So oxytocin could modify the probability for a relapse in alcohol dependent patients.
The aim of the present study is to investigate the influence of the oxytocin system on craving processes in social drinkers. This should be done in a challange study using intranasal oxytocin and placebo in a cross over design.
We want to measure via a fMRI study if intranasal oxytocin modifies participants subjectiv alcohol craving and the activation of the mesolimbic reward system during a confrontation with alcohol associated cues in a special fMRI paradiagma. Additionally, participants reaction on different emotional faces were measured.
The study is designed as a double blind placebo controlled investigation with two measuring days.
At one measuring day the participants received 24 IU Oxytocin intranasal before the fMRI. At the second measuring day the participants received an intranasal placebo medication before the fMRI. The fMRI starts 45 minutes after the participants received the medication.

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Organizational Data

  •   DRKS00009253
  •   2017/01/16
  •   [---]*
  •   yes
  •   Approved
  •   2015-540N-MA, Medizinische Ethik-Kommission II Medizinische Fakultät Mannheim der Universität Heidelberg
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Secondary IDs

  • [---]*
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Health Condition or Problem studied

  •   F10.2 -  Mental and behavioural disorders due to use of alcohol; Dependence syndrome
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Interventions/Observational Groups

  •   24 IE Oxytocin intranasal
    After receiving the intranasal medication the fMRI take place (Duration: 35 minutes)
  •   Intranasal Placebo
    After receiving the intranasal medication the fMRI take place (Duration: 35 minutes)
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Characteristics

  •   Interventional
  •   [---]*
  •   Randomized controlled trial
  •   Blinded
  •   patient/subject, investigator/therapist
  •   Placebo
  •   Basic research/physiological study
  •   Crossover
  •   N/A
  •   N/A
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Primary Outcome

Primary end point:

Differences in the functional brain activity between the oxytocin and the placebo condition during confrontation with alcohol associated cues

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Secondary Outcome

Secunary end point:

Differences in subjective craving between the oxytocin and the placebo condition during confrontation with alcohol associated cues (as measured with a visual analoge scale)

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
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Recruitment

  •   Actual
  •   2016/02/01
  •   25
  •   Monocenter trial
  •   National
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Inclusion Criteria

  •   Male
  •   18   Years
  •   65   Years
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Additional Inclusion Criteria

- Age: Between 18 and 65 years
- male gender
- Fully Informed Consent
- ability to take part in a fMRI
- Written Informed Consent
- Minimum 2 drinking days per week

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Exclusion Criteria

- No fully Informed Consent
- No written Informed Consent
- Female gender
- Age under 18 years ord over 65 years
- psyciatric disorders of axis I (according to DSM IV or ICD 10 except for nicotine dependence.
- Severe iinternal and neurological comorbities
- medication with interacts with oxytocin
- current drug abuse/dependence except for nicotine
- alcoholization at the measuring days
-contraindications for fMRI
.

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Addresses

  • start of 1:1-Block address primary-sponsor
    • Zentralinstitut für Seelische GesundheitKlinik für Abhängiges Verhalten und Suchtmedizin
    • Mr.  Prof. Dr. med.  Falk  Kiefer 
    • J5
    • 68159  Mannheim
    • Germany
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    • Zentralinstitut für Seeelische GesundheitKlinik für Abhängiges Verhalten und Suchtmedizin
    • Ms.  Dr. med.  Anne  Koopmann 
    • J5
    • 68159  Mannheim
    • Germany
    end of 1:1-Block address scientific-contact
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    end of 1:1-Block address contact scientific-contact
  • start of 1:1-Block address public-contact
    • Zentralinstitut für Seelische GesundheitKlinik für Abhängiges Verhalten und Suchtmedizin
    • Ms.  Dr. med.  Anne  Koopmann 
    • J5
    • 68159  Mannheim
    • Germany
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Sources of Monetary or Material Support

  • start of 1:1-Block address materialSupport
    • Klinik für abhängiges Verhalten und SuchtmedizinZentralinstitut für seelische Gesundheit
    • Mr.  Prof. Dr. med.   Falk  Kiefer 
    • Quadrat 5 5
    • 68159  Mannheim
    • Germany
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Status

  •   Recruiting complete, follow-up complete
  •   2017/01/09
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Trial Publications, Results and other Documents

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* This entry means the parameter is not applicable or has not been set.