Trial document




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  DRKS00019048

Trial Description

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Title

Open-Label Placebo Application in Addition to Standard Therapy in order to increase therapeutic Benefits during Treatment of adolescents with Major Depression

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Trial Acronym

OLP-Pilot

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URL of the Trial

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Brief Summary in Lay Language

Major depressive disorders (MDD) are among the most common life-shortening diseases worldwide. Particularly considerable is the lack of effective pharmacological treatment options especially for children and adolescents with MDD. Notably, the mean effect size for approved antidepressants is hardly higher than for placebos. Interestingly, children and adolescents with MDD show in clinical trials of second and newer generation antidepressants higher responses than adults towards placebos and the placebo response rates are pronounced, which argues towards a therapeutic use. In addition, the application of antidepressants bears a risk for marked side effects and supports in view of safety considerations the clinical relevance of the proposed open label placebo pilot-study.
We want to explore in this randomized, single-blind pilot study (n=40), whether an open label placebo application creates a placebo effect leading to a reduction of the depression severity in adolescents with MDD. We will compare two in-patient study arms of adolescents with MDD: An open-label-placebo- arm and a „treatment-as-usual arm (TAU). All patients will be treated according to the actual German treatment guidelines; the intervention arm will receive placebos on top of treatment, irregardless of the treatment regime. The study will take place in the “Klinik für Psychiatrie, Psychosomatik und Psychotherapie des Kindes- und Jugendalters, LVR Klinikum Essen, Universität Duisburg-Essen”. Data collection will entail depression severity by means of the Children's Depression Rating Scale-Revised (CDRS-R) and in parallel by means of the self-reported Beck’s Depresson Inventary (BDI-II).
To our knowledge, this approach has not yet been pursued, we thus hypothesize that the application of open-label-placebo (study-arm OLP) for four weeks on-top off standard therapy will lead to significant and clinically relevant differences of clinician rated scores of depression severity (CDRS-R) in relation to the study arm without placebo treatment (TAU).

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Brief Summary in Scientific Language

Depressive disorders are one of the most common life-shortening diseases worldwide (Ferrari et al., 2013; WHO, 2012) and may severely burden patients, their family members and employers (Stewart, Ricci, Chee, Hahn, & Morganstein, 2003) ], as well as the public health systems (Sobocki, Jonsson, Angst, & Rehnberg, 2006). Depressive disorders hit about 1- 3% pre-pubertal children and about 6% of post-pubertal children and adolescents (Dolle & Schulte-Korne, 2014). Symptoms of mental disorders frequently arise in childhood or adolescence and persist into adulthood (Jones, 2013) Cheung, Kozloff, & Sacks, 2013; Hebebrand, 2010; Holtmann et al., 2011; Jane Costello, Erkanli, & Angold, 2006; Jonsson et al., 2011; Karow et al., 2013; Lambert et al., 2013). The medical-need for effective, patient-centered and cost-effective therapies is high (Reynolds et al., 2012) especially also for children and adolescents (Essau, 2005; Reissner et al., 2013). The mean effect size (0.3) (reduction of depressive symptoms in RCTs with children and adolescents) for currently approved antidepressants is hardly higher than for placebos (Cipriani et al., 2016; Gibertini, Nations, & Whitaker, 2012).
Interestingly, children and adolescents with MDD show in clinical trials of second and newer generation antidepressants higher responses towards placebos (Bridge, Birmaher, Iyengar, Barbe, & Brent, 2009; Bridge et al., 2007; Cipriani et al., 2016; Cohen et al., 2008; Locher, Koechlin, et al., 2017; Parellada et al., 2012; Tsapakis, Soldani, Tondo, & Baldessarini, 2008) than adults (Furukawa et al., 2016).
We (Meister et al., 2018) performed recently a systematic review and meta-regression analysis on placebo response rates at end of treatment and potential modifiers in 24 placebo controlled double-blind RCTs (2229 patients in placebo arm) of second and newer generation antidepressants for MDD in children and adolescents. Treatment durations ranged from six to twelve weeks. Our study confirmed a high pooled clinician rated placebo response rate (reduction of depressive symptoms) at a rate of 45% (95% CI: 41–50%) which was higher than that obtained in a large meta-analysis of 252 RCTs in adults (36%; 95% CI 35–37%) focusing on second-generation antidepressants (Furukawa et al., 2016).
The use of placebo treatments in a clinical context is constrained by ethical and legal issues regarding the deceptive information traditionally associated with its application, an issue even more complicated in a pediatric context. One way out of these constraints is the open-label application of placebos without deception (Evers et al., 2018) on top-off approved standard therapies.
Recent studies have shown that OLP treatments can be effective in adults (Charlesworth et al., 2017; Locher, Frey Nascimento, et al., 2017). Effectiveness has been documented for irritable bowel syndrome (Kaptchuk et al., 2010), acute migraine attacks (Kam-Hansen et al., 2014), and low back pain (Carvalho et al., 2016). A first study in adults with MDD was performed in Harvard (Kelley et al., 2012). After two weeks, Kelley et al. did not found significant differences in eleven patients treated with open-labeled placebos versus nine patients on a waiting list. However, the observed effect-size amounted to 0.54 with regard to an improvement of the HAMD-17-Scores (Hamilton Depression Scale-17; p=0.26).
The effect of placebos is beyond dispute and leads to significant improvements in numerous diseases and disorders (Kaptchuk et al., 2010). For a long time it was assumed that placebos need the usual deceptive application to exert their effects. Recent studies revealed that deception is not mandatory (Carvalho et al., 2016; Kaptchuk et al., 2010).
To our knowledge, this approach has not yet been pursued, we thus hypothesize that the application of open-label-placebo (study-arm OLP) for four weeks on-top off standard therapy will lead to significant and clinically relevant differences of clinician rated scores of depression severity (CDRS-R) in relation to the study arm without placebo treatment (TAU).

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Organizational Data

  •   DRKS00019048
  •   2019/11/14
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  •   yes
  •   Approved
  •   19-8683-BO, Ethik-Kommission der Medizinischen Fakultät der Universität Duisburg-Essen
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Secondary IDs

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Health Condition or Problem studied

  •   F32 -  Depressive episode
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Interventions/Observational Groups

  •   Application of open-label Placebos (two times per day) on top off standard therapy (study-arm: OLP)
  •   Control Group with treatment as usual (study-arm: TAU)
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Characteristics

  •   Interventional
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  •   Randomized controlled trial
  •   Blinded
  •   investigator/therapist
  •   Active control (effective treament of control group)
  •   Treatment
  •   Parallel
  •   N/A
  •   N/A
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Primary Outcome

Depression scores after 28 days by means of CDRS-R

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Secondary Outcome

Depression scores after 28 days by means of BDI-II

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
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Recruitment

  •   Planned
  •   2019/11/25
  •   40
  •   Monocenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   16   Years
  •   18   Years
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Additional Inclusion Criteria

Major depression; diagnosis according to DSM-5, ascertained by a board certified child and adolescent psychiatrist or psychotherapist by means of a semi-structured diagnostic interview (Kinder-DIPS-Open-Access; parent and child/adolescent version; Margraf et al., 2017)
Informed consent from parents and patient

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Exclusion Criteria

Any of the following co-morbide (actual or life-time) mental disorders: eating disorder, schizophrenia, manic episode(s)

Actual somatic or neurologic disease incuding epilepsia
IQ < 85
Inability to comprehend or speak German
Current treatment with antidepressants
Known lactose intolerance
Known allergies against other components of the placebo pills (Lactose-monohydrate, cellulose powder, magnesiumstearat (Ph. Eur.), and microcrystalline cellulose)

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Addresses

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    • Universitätsklinikum Essen
    • Mr.  Thorsten  Kaatze 
    • Hufelandstraße 55
    • 45147  Essen
    • Germany
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    • Klinik für Psychiatrie, Psychosomatik und Psychotherapie des Kindes- und Jugendalters,LVR-Klinikum Essen, Kliniken der Universität Duisburg-Essen
    • Mr.  Prof. Dr.  Johannes  Hebebrand 
    • Wickenburgstr. 21
    • 45147  Essen
    • Germany
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    • Klinik für Psychiatrie, Psychosomatik und Psychotherapie des Kindes- und Jugendalters,LVR-Klinikum Essen, Kliniken der Universität Duisburg-Essen
    • Mr.  Christian  Engelhardt 
    • Wickenburgstr. 21
    • 45147  Essen
    • Germany
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Sources of Monetary or Material Support

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    • Stiftung Universitätsmedizin Essen
    • Hufelandstr. 55
    • 45147  Essen
    • Germany
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    • Klinik für Psychiatrie, Psychosomatik und Psychotherapie des Kindes- und Jugendalters,LVR-Klinikum Essen, Kliniken der Universität Duisburg-Essen
    • Mr.  Prof. Dr. med  Johannes  Hebebrand 
    • Wickenburgstr. 21
    • 45147  Essen
    • Germany
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Status

  •   Recruiting planned
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Trial Publications, Results and other Documents

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