Trial document




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  DRKS00009296

Trial Description

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Title

Placebo and Nocebo Effects
in Patients With Takotsubo
Cardiomyopathy and Heart-Healthy
Controls

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Trial Acronym

CaRe

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URL of the Trial

https://www.frontiersin.org/articles/10.3389/fpsyt.2019.00549/full

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Brief Summary in Lay Language

The current study examines the effect of neutral, positive, and negative suggestions in patients with Stressinduced Cardiomyopahty compared to heart-healthy controls.
The etiology of Stressinduced Cardiomyopathy, also called takotsubo cardiomyopathy (TTC) is not yet fully explained. It is assumed that a previous extremely stressful life event triggers an unnatural and strong stress-response that in turn causes the changes of the heart.

Simultaneously, placebo research could prove that a medication’s effect always comprises of the pharmacological effect (viz. the effect caused due to the chemical structure of the administered substance) and the psychological effect – referred to as placebo effect.

Therefore saline solution was given to the particants three times in a row, with different explanations, a neutral, a positive (supporting), and a negative (burdening) explanation.

Only the negative intervention induced an effect for the whole group of participants viz. higher levels of subjective stress ratings and an SBP increase could be obsereved.

No differences could be found between TTCs and controls. Therefore our findings can't support the assumption of an exaggerated activation of the SNS as a discrrimantory factor fo TTC, but promotes, besides medical care, psychological support for patients with TTC.

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Brief Summary in Scientific Language

The etiology of takotsubo cardiomyopathy (TTC)—a rare, reversible, and acquired form of cardiac diseases—is not yet fully explained. An exaggerated activation of the sympatheticnervous-system (SNS) following stressful psychosocial life events is discussed to be of key importance. In this experimental study, we tested whether TTC patients, compared
to heart-healthy controls, respond more strongly to supporting placebo interventions and
stressful nocebo interventions targeting cardiac function. In a single experimental session,
20 female TTC patients and 20 age matched (mean age 61.5 years, ± 12.89) catheterconfirmed heart-healthy women were examined. Saline solution was administered three
times i.v. to all participants, with the verbal suggestion they receive an inert substance with
no effects on the heart (neutral condition), a drug that would support cardiac functions
(positive condition), and a drug that would burden the heart (negative condition). Systolic
and diastolic blood pressure (DBP/SBP), heart rate (HR), endocrine markers cortisol
(µg/dl), copeptin (pmol/l), and subjective stress ratings (SUD) were assessed to examine
alterations of the SNS and the hypothalamic–pituitary–adrenal axis (HPA). Before and after
each intervention SUD was rated. One pre and three post serum cortisol and copeptin
samples were assessed, and a long-term electrocardiogram as well as non-invasive,
continuous blood pressure was recorded. The study design elucidated a significant
increase of SUD levels as a response to the nocebo intervention, while perceived stress
remained unaffected during the preceding neutral and positive interventions. Increasing
SUD levels were accompanied by higher SBP and an anticipatory increase of HR shortly
prior to the nocebo intervention. SBP increased also as a response to positive verbal
suggestions (Bonferroni-corrected p-values > .05). Alterations of cortisol and copeptin
due to the interventions and significant placebo effects failed to appear. Interestingly no differences between TCC patients and controls could be found.These findings do not
support the assumption of an exaggerated activation of the SNS as a discriminatory
factor for TTC. Since especially the nocebo intervention revealed negative subjective and
objective effects, our results underscore the urgent need to consider carefully the impact
of verbal suggestions in the interaction with cardiac patients in daily clinical routine.

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Organizational Data

  •   DRKS00009296
  •   2015/10/27
  •   [---]*
  •   yes
  •   Approved
  •   341/15, Ethik-Kommission der Fakultät für Medizin der Technischen Universität München
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Secondary IDs

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

  •   I42.88 -  [generalization I42.8: Other cardiomyopathies]
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Interventions/Observational Groups

  •   Arm 1: Patients with Stressinduced Cardiomyopathy (according to Mayo clinic diagnostic criteria)
  •   Arm 2: Heart-healthy controls (katheder-confirmed) matched according to age and sex
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Characteristics

  •   Interventional
  •   [---]*
  •   Non-randomized controlled trial
  •   Blinded
  •   patient/subject, assessor, data analyst
  •   Other
  •   Basic research/physiological study
  •   Parallel
  •   N/A
  •   N/A
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Primary Outcome

Systolic blood pressure, diastolic blood pressure, heart rate, subjective units of distress

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Secondary Outcome

Copeptin, cortisol

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • Medical Center 
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Recruitment

  •   Actual
  •   2015/11/09
  •   40
  •   Monocenter trial
  •   National
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Inclusion Criteria

  •   Female
  •   18   Years
  •   75   Years
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Additional Inclusion Criteria

Women, diagnosed with TTC, and 20 volunteers (CG) free of significant coronary artery disease (vessel stenosis ≤30%, confirmed via
heart catheterization in the past)
TTC patients diagnosed regarding Mayo Clinic’s diagnostic criteria for akotsubo Cardiomyopathy.

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Exclusion Criteria

Participants with significantly decreased ejection fraction (<55%) or low German proficiency, malignant primary disease

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Addresses

  • start of 1:1-Block address primary-sponsor
    • Klinik und Poliklinik für Psychosomatische Medizin und Psychotherapie, Klinikum rechts der Isar der Technischen Universität, München
    • Mr.  Dr. med.  Joram  Ronel 
    • Ismaninger Str. 22
    • 81675  München
    • Germany
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    • Institut für Medizinische Psychologie der Ludwig-Maximilians Universität, München
    • Ms.  PD Dr. med.  Karin  Meissner 
    • Goethestr. 31
    • 80336  München
    • Germany
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    • Klinik für Herz- und Kreislauferkrankungen, Deutsches Herzzentrum München
    • Mr.  PD Dr. med.  Christof  Burgdorf 
    • Lazarettstr. 36
    • 80636  München
    • Germany
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    • Institut für Medizinische Psychologie der Ludwig-Maximilians Universität, München
    • Ms.  Elisabeth  Olliges 
    • Goethestr. 31
    • 80336  München
    • Germany
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Sources of Monetary or Material Support

  • start of 1:1-Block address materialSupport
    • Klinik und Poliklinik für Psychosomatische Medizin und Psychotherapie, Klinikum rechts der Isar der Technischen Universität, München
    • Mr.  Dr.  Joram  Ronel 
    • Ismaninger Str. 22
    • 81675  München
    • Germany
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Status

  •   Recruiting complete, follow-up complete
  •   2016/03/28
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* This entry means the parameter is not applicable or has not been set.