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Open Access Study protocol

A genotype-specific, randomized controlled behavioral intervention to improve the neuroemotional outcome of cardiac surgery: study protocol for a randomized controlled trial

Daniela Hauer1*, Iris-Tatjana Kolassa2, Rüdiger Paul Laubender3, Ulrich Mansmann3, Christian Hagl4, Benno Roozendaal5, Dominique J-F de Quervain6 and Gustav Schelling1

Author Affiliations

1 Department of Anaesthesiology, Ludwig-Maximilians University, Munich 81377, Germany

2 Clinical and Biological Psychology, Institute of Psychology & Education, University of Ulm, Ulm 89069, Germany

3 Institute of Medical Informatics, Biometry, and Epidemiology, Ludwig-Maximilians University, Munich 81377, Germany

4 Department of Cardiac Surgery, Ludwig-Maximilians University, Munich 81377, Germany

5 Department of Cognitive Neuroscience, Radboud University Nijmegen Medical Centre and Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, Nijmegen, 6500 HB Nijmegen, The Netherlands

6 Division of Cognitive Neuroscience, University of Basel, Basel 4056, Switzerland

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Trials 2013, 14:89  doi:10.1186/1745-6215-14-89

Published: 1 April 2013

Abstract

Background

Cardiac surgery is one of the most commonly performed surgical procedures worldwide with >700,000 surgeries in 2006 in the US alone. Cardiac surgery results in a considerable exposure to physical and emotional stress; stress-related disorders such as depression or post-traumatic stress disorder are the most common adverse outcomes of cardiac surgery, seen in up to 20% of patients. Using information from a genome-wide association study to characterize genetic effects on emotional memory, we recently identified a single nucleotide polymorphism of the glucocorticoid receptor gene (the Bcll single nucleotide polymorphism) as a significant genetic risk factor for traumatic memories from cardiac surgery and symptoms of post-traumaticstress disorder. The Bcll high-risk genotype (Bcll GG) has a prevalence of 16.6% in patients undergoing cardiac surgery and is associated with increased glucocorticoid receptor signaling under stress. Concomitant animal experiments have confirmed an essential role of glucocorticoid receptor activation for traumatic memory formation during stressful experiences. Early cognitive behavioral intervention has been shown to prevent stress-related disorders after heart surgery.

Methods/Design

The proposed study protocol is based on the above mentioned earlier findings from animal experiments and preclinical studies in volunteers. Patients (n = 872) will be genotyped for the Bcll single nucleotide polymorphism before surgery, which should result in 120 homozygous high-risk carriers of the Bcll GG allele and 240 randomly selected low-risk heterozygous or non-carriers of the single nucleotide polymorphism. All patients will then undergo randomization to either cognitive behavioral intervention or a control intervention consisting of non-specific general information about the role of stress in heart disease. The primary efficacy endpoint will be post-traumatic stress levels at one year after surgery as determined by a standardized questionnaire that has been specifically validated in patients after critical illness.

Discussion

The proposed randomized controlled trial intends to demonstrate that a preoperatively administered minimal cognitive behavioral intervention targeted to homozygous carriers of the Bcll *G high-risk allele reduces traumatic memories and post-traumatic stress disorder symptoms after heart surgery to a level seen in non-carriers of the mutation, and thus improves the neuroemotional outcome of cardiac surgery.

Trial registration number

The trial will be registered at http://www.clinicaltrials.gov/ webcite before commencing with the study.

Keywords:
Cognitive behavioral intervention; Genotyping; Glucocorticoid receptor; Personalized medicine; Post-traumatic stress disorder; Prophylaxis; Single nucleotide polymorphism