Trial document




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  DRKS00016872

Trial Description

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Title

Practicability Study for the Multimodal Outcome Study of Psychoanalyses of Chronically Depressed Patients with Early Trauma

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Trial Acronym

MODE

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URL of the Trial

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Brief Summary in Lay Language

SHORT SUMMARY

The initial phase of this multi-center, multi-methods project MODE is devoted to the question if the planned mutlicentric international study will be feasible. MODE will examine outcomes of manualized high frequent psychoanalytic psychotherapy (3-4 weekly sessions, Intervention I) versus manualized, low frequent psychoanalytic psychotherapy (1 session a week, Intervention II) for early traumatized, chronically depressed patients. Patients are to be randomly assigned to one of the two treatment conditions. The major hypothesis of the large study will be that for this group of patients, high frequent psychoanalytic treatments will lead to better outcome in comparison to low frequent psychoanalytic treatment. Psychological and neurobiological measures are combined studying the outcomes of the therapies.
The goals of this initial phase are simple, namely to determine whether the international, multicentric study MODE is really practicable in Frankfurt/Bochum; Lausanne and Los Angeles. Its major hypotheses are thus clear – namely that the MODE study can be carried out. Essential activities in this initial phase will include obtaining IRB approval, building a network of researchers and clinicians, writing manuals, clarifying and testing fMRI protocols, and evaluating first results.

The outcomes of psychoanalytic short-term therapies according to evidence-based-medicine criteria have meanwhile been confirmed by many studies. In contrast, only a few studies are available on the effects of long-term therapies and psychoanalyses. Multi-Level Outcome Study of Psychoanalyses of Chronically Depressed Patients with Early Trauma (MODE) follows on from the results of the LAC Depression Study, which showed that chronically depressed patients can be successfully treated with psychoanalytic (PAT) and cognitive-behavioral long-term therapy (CBT) (high effect sizes in symptom reduction, high remission rates etc.). It was found that structural changes (measured with Operationalized Psychodynamic Diagnostics, OPD) can only be observed in PAT but not in CBT after 3 years of treatment (Leuzinger-Bohleber, et al., 2918, 2019). One unexpected result of the LAC study was that around 80% of chronic depressives suffered from early trauma and responded particularly well to high frequency psychoanalyses. One of MODE's aims is to show that this group of hard-to-treat patients who respond poorly to short-term therapies and low-frequency treatments are accessible to high-frequency treatments. In other words: the study focuses on the question whether there are certain patient groups that require high-frequency treatments in order to be therapeutically accessible at all.
In addition, it will be investigated whether and how symptomatic and structural changes in this patient group will also be investigated with neurobiological instruments. For this reason, MODE considers neurobiological (e.g. fMRI) and clinical-psychoanalytical (e.g. changes in dreams) observation methods in addition to the usual (psychological) instruments of comparative psychotherapy research. From October 2017-June 2018 a first feasibility study was conducted to explore the potential for the MODE study. That feasibility study also had positive results.

The study proposed here is the initial phase of this multi-center, multi-methods project MODE. MODE will examine outcomes of psychoanalysis (frequent sessions) versus psychoanalytic psychotherapy (less frequent sessions) for early traumatized, chronically depressed patients. Patients are to be randomly assigned to one of the two treatment conditions. The major hypothesis of the large study will be that for this group of patients, frequent treatment is necessary, resulting in demonstrably better outcomes, achieved more rapidly, in comparison to less frequent psychoanalytic treatment. Treatment manuals will be created and used. Treatment progress will be followed in relation to symptom reduction (using standard psychological measures), structural change (defined by psychoanalytic methods), and neurobiological change (assessed via fMRI). Centers for the first phase of the study will be in Los Angeles, Frankfurt a.M./Bochum and Lausanne.

The goals of this initial phase are simple, namely to determine whether MODE is really practicable. Its major hypotheses are thus clear – namely that the MODE study can be carried out. Essential activities in this initial phase will include obtaining IRB approval, building a network of researchers and clinicians, writing manuals, clarifying and testing fMRI protocols, and evaluating results. This application specifically focuses on activities that will be conducted in Germany (Frankfurt /Bochum) in Lausanne and Los Angeles.

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Brief Summary in Scientific Language

ENGLISH LONGER SUMMARY

This study is the initial phase of a planned international, multi-center project, the Multi-Level Outcome Study of Psychoanalyses of Chronically Depressed Patients with Early Trauma (MODE). MODE will examine outcomes of manualized, high frequent psychoanalytic longterm psychotherapies (3-4 sessions a week, Intervention I) versus low frequent psychoanalytic longterm psychotherapies (1 session a week) for a specific patient population. Patients are to be randomly assigned to one of the two treatment conditions. The patient population consists of chronically depressed individuals who have experienced childhood trauma. The major hypothesis of the large study will be that for this group of difficult-to-treat patients, high frequent treatment will lead to sustaining brain and psychic transformations with a higher probability than low frequent treatments. Therefore, it is expected that the outcome of high frequent treatments will be better in comparison to low frequent psychoanalytic treatment. Primary Outcome measures are anatomical and neurobiological changes in the brain as well as so called „structural changes“ (measured by the Scales of Psychological Capacities and the Self-reflective Functioning Scales). Secondary Outcome measures are symptom reduction (BDI, QIDS, MADRS, DEQ), social functioning (GAF), coping with trauma (CTQ, PCL-5), changes in personality (IIP) and working alliance (WAI). The participating centers of the study are Frankfurt/Bochum (Germany), Lausanne (Switzerland) and Los Angeles (USA)

The MODE project draws on the findings of the LAC Depression Study, a randomized controlled study comparing the outcomes of long-term psychoanalytic and cognitive behavioral psychotherapies with chronically depressed patients. (see Leuzinger-Bohleber et al., 2018, 2019 a, b,c,) This German multi-center study, conducted in Frankfurt, Mainz, Berlin and Hamburg, lead to statistically significant reduction of depressive symptoms, high effect sizes and a high portion of complete remission. Participants benefitting from the psychoanalytic psychotherapy showed greater „structural changes“. A surprising finding was that more than 80% of the chronically depressed patients had suffered from severe childhood trauma. Subsequently, a first investigation of the feasibility was conducted with experts to explore the potential for the MODE study. That feasibility study also had positive results.

What is proposed now is an initial phase of MODE to determine if it is really practicable. The goals of this initial phase are simple, and its major hypothesis clear – namely that the MODE study can be carried out. (see Time Schedule below). Essential activities in this initial phase will include obtaining IRB approvals, building a network of researchers and clinicians, writing manuals, clarifying and testing fMRI protocols, and evaluating results.

The Initial Phase continues until the end of June 2019, at which time a decision will be reached regarding the practicability of MODE and if an application for the funding of MODE should be written until end of 2019).

Hypothesis 1 (Initial Phase): It will be possible to build a network of researchers and clinicians, centered in Frankfurt /Bochum, Lausanne and Los Angeles, sufficient to conduct the main MODE study.

Hypothesis 2 (Initial Phase): It will be possible to recruit subjects for fMRI study and conduct tests of the Cyberball and the anatomical measures

For the MODE Study itself, the aims and hypotheses are as follows:

AIM 1: To show that a certain group of hard-to-treat patients (chronically depressed patients with childhood trauma) who respond poorly to short-term therapies and low-frequency treatments, are accessible to high-frequency treatments. In other words: the study focuses on the question of whether there are certain patient groups that require high-frequency treatments in order to be therapeutically accessible at all.

AIM 2: To compare the efficacy of high frequency psychoanalysis to that of low frequency psychoanalytic psychotherapy for chronically depressed patients with childhood trauma.

AIM 3: To investigate whether and how symptomatic and structural changes in this patient group can also be detected with neurobiological instruments. For this reason, MODE considers neurobiological (e.g. fMRI) methods in addition to the usual (psychological) instruments of comparative psychotherapy research.

AIM 4: To explore the possibility that behavioral, psychological and neurobiological measurements of patients in this group in high frequency psychoanalytic treatment may lead to interesting findings as early as the end of one year of treatment.

MODE Hypotheses:
Hypothesis 1: Clinical Change
1a) Both treatments (high frequency and low frequency) will lead to clinical improvement, including:
1.a.i. a reduction of depressive symptoms (QIDS, BDI-2)
1.a.ii. structural changes (measured by the Scales of Psychological Capacities and by the Operationalized Psychodynamic Diagnostics, OPD)
1.a.iii. changes in the manifest dreams in the dream diaries according to the Dream Coding System by Moser & von Zeppelin (1996)
1b) High frequency psychoanalyses compared to low frequency treatment will experience greater clinical improvement over the course of the study.
1.b.i. High frequency psychoanalyses ill lead to faster symptom reduction than low frequency psychotherapies.
1.b.ii. Clinical improvement for chronically depressed and severely traumatized patients in high frequency psychoanalytical treatments (3-5 weekly sessions) will be correlated with structural intrapsychic changes, allowing them to re-gain a basic trust in self-agency as well as in a helping Other (Bohleber, 2010). These changes will be significantly greater in the high frequency treatment group than in the low frequency treatment group.
1.b.iii. Patients in the high frequency treatment group will experience greater improvement in social and working behavior after one year, in contrast to those in the low frequency treatment group.

Hypothesis 2: Neurobiological Change
2a) High frequency psychoanalyses will show differential brain activity in the fMRI Cyberball paradigm for social exclusion compared to low frequency treatment
2.a.i. The depressed patients in the MODE sample will show differential patterns of activation in response to exclusion in the Cyberball paradigm, compared to normal controls (Jankowski et al., 2018). Relevant areas will include the anterior cingulate cortex (ACC), the insula, and the ventromedial prefrontal/orbitofrontal cortex, areas that are associated with emotion regulation, reward processing, and social pain (see Cacioppo et al., 2013; Rotge et al., 2015; Wang et al., 2017 for recent reviews). These findings are expected to:
• normalize with high frequency treatment
• correlate with and statistically mediate the effects of differing treatment frequencies on: (1) symptom severity and psychoanalytic measures of basic trust; (2) pathological DMN hyperactivation; and (3) reduced trust in the “Trust Game” paradigm.
2b) High frequency psychoanalyses will show differential brain activity in resting state fMRI connectivity compared to low frequency treatment
2.b.i. Depressed individuals will show an increased activation of DMN (Default Mode Network) compared to controls in resting state fMRI (Hamilton et al., 2013). These patterns of DMN activation are expected to normalize in patients during the course of treatment in high frequency psychoanalysis in as little as one year.
2c) Similar to our prior findings in chronically depressed patients in a randomized controlled trial of medication therapy, changes in the thickness of the cortical mantle, representing therapy-induced, neuroplastic compensatory changes in brain structure, will normalize as well as correlate with clinical improvement in the chronically depressed patients in the study. These changes will be greatest in those assigned to high compared with low frequency treatment.

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Organizational Data

  •   DRKS00016872
  •   2019/03/12
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  •   yes
  •   Approved
  •   463/13, Ethikkommission des Fachbereichs Humanmedizin der Johann-Wolfgang-Goethe-Universität Frankfurt am Main
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Secondary IDs

  •   U1111-1229-2321 
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Health Condition or Problem studied

  •   F33 -  Recurrent depressive disorder
  •   Early traumatization, measured by
    CTQ (Childhood Trauma Questionnaire)
    PCL-R (Trauma Questionnaire for Adults)
    CECA.Q (Childhood Experience of Care and Abuse Questionnaire)
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Interventions/Observational Groups

  •   Psychoanalytical longterm treatment with 1 weekly session
  •   Psychoanalytical longterm treatment with 3-4 weekly session
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Characteristics

  •   Interventional
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  •   Randomized controlled trial
  •   Blinded
  •   assessor, data analyst
  •   Active control (effective treament of control group)
  •   Treatment
  •   Parallel
  •   N/A
  •   N/A
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Primary Outcome

Neurobiological Outcome measure:
Similar to our prior findings in chronically depressed patients in a randomized controlled trial of medication therapy, changes in the thickness of the cortical mantle, representing therapy-induced, neuroplastic compensatory changes in brain structure, will normalize. The amount of normalization will correlate with clinical improvement in the chronically depressed patients in the study as measured by the psychoanalytical outcome measure (see below). These changes will be higher in patients assigned to high as compared with low frequency treatment.
Psychoanalytical Outcome measure:
Based on prior findings in several outcome studies, patients with high frequency treatment will show greater structural changes (as measured by the Scales of Psychological Capacities, SPC, combined with the Self Reflecting Functioning Scales) than patients with low frequency treatment.

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Secondary Outcome

T0 (prior to intervention):
Interviews:
- psychoanalytic Assessment Interview by clincian
- SKID by independent interviewer
- Global Assessment Scale (GAS)
- OPD-Interview by trained OPD interviewer (incl. 3 questions from Adult Attachment Interview)

Questionnaire:
- BDI (Beck Depression Inventory)
- QIDS (Quick Inventory of depressive Symptoms; self and independent assessment)
- MADRS (Montgomery and Amberg Depression Rating Scale)
- DEQ (Depressive Experience Questionnaire)
- CTQ (Child Trauma Questionnaire)
- PCl-5 (PTSD Checklist)
- CECA.Q (Childhood Experience of Care and Abuse Questionnaire)
- IIP (Inventory Interpersonal Problems)
- SCL-90-R (Symptom Checklist)
- WAI (Work Ability Index)
- Dream Diary

fMRI
- Resting State
- different modalities for measuring neuroplasticity by perfusion imaging (cortical thickness, diffusion)

T1 (1 year post intervention)
Interviews:
- LIFE by independent interviewer
- Global Assessment Scale (GAS)
- OPD-Interview by trained OPD interviewer (incl. 3 questions from Adult Attachment Interview)

Questionnaire:
- BDI (Beck Depression Inventory)
- QUIDS (Quick Inventory of depressive Symptoms; self and independent assessment)
- MADRS (Montgomery and Amberg Depression Rating Scale)
- DEQ (Depressive Experience Questionnaire)
- CTQ (Child Trauma Questionnaire)
- PCl-5 (PTSD Checklist)
- CECA.Q (Childhood Experience of Care and Abuse Questionnaire)
- IIP (Inventory Interpersonal Problems)
- SCL-90-R (Symptom Checklist)
- WAI (Work Ability Index)
- Dream Diary

fMRI
- Resting State
- different modalities for measuring neuroplasticity by perfusion imaging (cortical thickness, diffusion)

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Countries of Recruitment

  •   Germany
  •   Switzerland
  •   United States
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Locations of Recruitment

  • other 
  • University Medical Center 
  • other 
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Recruitment

  •   Planned
  •   2019/05/01
  •   45
  •   Multicenter trial
  •   International
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Inclusion Criteria

  •   Both, male and female
  •   30   Years
  •   50   Years
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Additional Inclusion Criteria

Diagnosis of major depression or dysthymia (based on Structural Clinical Interview-SCID) for at least 24 months
QIDS-C score > 9, BDI 2 > 17
Age: 30-50 years
CTQ: at least trauma at one of the subscales (selfratings of the patients, ratings of SCID interviewer)
At least one unsuccessful short-term psychotherapy and one drug therapy
Sufficient knowledge of local language
Informed consent to study protocol
Willing to be treated without antidepressand medication for one year (except in emergency situations)

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Exclusion Criteria

Current or past psychotic symptomatology, schizoaffective, schizophrenic, or bipolar affective disorder
Substance dependence current or during the last three years
Dementia
Borderline, schizotypal and antisocial personality disorder
Acute suicidality
Restriction of intellectual capacity
Serious physical illness that strongly affects the depression or is causal for the depression
Concurrent psychotherapeutic treatment

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Addresses

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    • International Psychoanalytic Association
    • Lexicon, Unit B, Book House, 261a City Road
    • EC1V 1AH  London
    • United Kingdom
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    • IDeA-Zentrum
    • Ms.  Prof.  Marianne  Leuzinger-Bohleber 
    • Am Ebelfeld 1A
    • 60488  Frankfurt
    • Germany
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    • Frankfurter Psychoanalytisches Institut (FPI)
    • Ms.  Dipl.-Psych.  Lisa  Kallenbach-Kaminski 
    • Myliusstr. 20
    • 60323  Frankfurt
    • Germany
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    • Frankfurter Psychoanalytisches Institut (FPI)
    • Ms.  Dr.  Andju  Labuhn 
    • Myliusstr. 20
    • 60323  Frankfurt
    • Germany
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Sources of Monetary or Material Support

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    • International Psychoanalytic Association
    • Lexicon, Unit B, Book House, 261a City Road
    • EC1V 1AH  London
    • United Kingdom
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Status

  •   Recruiting planned
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Trial Publications, Results and other Documents

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