Trial document




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  DRKS00008750

Trial Description

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Title

Add-on spironolactone for the treatment of schizophrenia

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Trial Acronym

SPIRO-TREAT

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URL of the Trial

[---]*

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Brief Summary in Lay Language

The main aim of this study is to investigate the efficacy of spironolactone (well-established diuretic, approved since more than 30 years) for the treatment of so called cognitive impairments in schizophrenia. Such cognitive impairments are e.g. deficits in logical thinking or memory functioning.

Background is that animal experiments (schizophrenia mouse model) have shown that spironolactone may be effective for this indication. Thus, the hypothesis is that spironolactone is more effective than placebo (medically ineffective) treatment) for the treatment of the already mentioned cognitive deficits. Male patients with schizophrenia with a duration of illness of at least 6 months can participate.

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Brief Summary in Scientific Language

The aim of the SPIRO-TREAT trial is to evaluate, whether an add-on treatment with spironolactone to the ongoing treatment in schizophrenia patients is more effective than a placebo treatment for the improvement of cognitive impairments and whether this effect is dose-related. For that reason, three groups will be compared: 100 mg spironolactone, 200 mg spironolactone and placebo (add-on, for three weeks). The primary endpoint is working memory improvement assessed by the n-back. Male schizophrenia patients can participate in this trials if they duration of illness is longer than 6 months.
The scientific rational for this trial is that animal experiments have shown that pharmacological inhibitors of the NRG1-ERBB4-PI3K-pathway are promising targets to develop new treatment concepts in schizophrenia. In this context, preclinical studies showed that spironolactone is such a strong and specific inhibitor of the aforementioned signal-pathway.

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Organizational Data

  •   DRKS00008750
  •   2015/06/09
  •   [---]*
  •   yes
  •   Approved
  •   32-15 fed, Ethik-Kommission der Medizinischen Fakultät der Ludwig-Maximilians-Universität München
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Secondary IDs

  •   2014-001968-35 
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Health Condition or Problem studied

  •   F20 -  Schizophrenia
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Interventions/Observational Groups

  •   100 mg spironolactone per day add-on to ongoing antipsychotic treatment for 3 weeks
  •   200 mg spironolactone per day add-on to ongoing antipsychotic treatment for 3 weeks
  •   Placebo add-on to ongoing antipsychotic treatment for 3 weeks
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Characteristics

  •   Interventional
  •   [---]*
  •   Randomized controlled trial
  •   Blinded
  •   patient/subject, investigator/therapist, assessor
  •   Placebo, Active control (effective treament of control group)
  •   Treatment
  •   Parallel
  •   IIb
  •   Yes
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Primary Outcome

Improvement of working memory in n-back after 3 weeks. n-Back will be assessed using a computer-based test with the 0, 1 and 2 back condition. The primary outcome will be measured after three weeks.

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Secondary Outcome

Improvement of other neurocognitive functions after 3 and 12 weeks (verbal memory, working speed), changes in psychopathology of PANSS (Positive and Negative Syndrome Scale) and CDSS (Calgary Depression Scale for Schizophrenia), changes in CGI (Clinical Global Impression) and GAF (Global Assessment of Functioning), occurrence of single side effects, changes of cortical inhibition, changes in ERBB4 metabolic pathway.

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
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Recruitment

  •   Actual
  •   2015/07/16
  •   81
  •   Multicenter trial
  •   National
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Inclusion Criteria

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

Male and female (with contraception) patients with schizophrenia (ICD-10 Criteria), no longer in acute phase of illness (PANSS Total ≤ 75, CGI ≤ 4), duration of illness > 6 months, guideline-based ongoing antipsychotic treatment in monotherapy or in combination treatment with maximum two antipsychotics if clinically required, stable medication for at least one week, aged 18 to 65, capacity to consent

Following a major protocol adaption, female subjects were also permitted (approved by IRB of LMU, 04.10.2016).

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Exclusion Criteria

Pregnancy, no contraception, current suicidality as well as injuries to others, severe neurological and internistic comorbidities, known and assumed non-compliance regarding intake of medication, current antipsychotic therapy with clozapine, antipsychotic treatment with a fully renal eliminable compound (amisulprid), known clinical necessity of antipsychotic combination treatment, no new dosing of mood stabilisers or antidepressants during 3-week intervention phase. An already existing mood stabiliser therapy (excluding lithium) or antidepressant therapy (excluding renal eliminable antidepressant) can be continued in unaltered dose. Alcohol- or substance abuse during the last 6 months before inclusion into study; nicotine and coffee are excluded. Epileptic seizures in anamnesis, known intolerance of the respective study medication, current anuresis or acute kidney failure, kidney insufficiency (creatinine clearance < 30 ml/min per 1.73 m² body surface, resp. serum-creatinine > 1.8 mg/dl), known clinically relevant hyperkalaemia or hyponatraemia, known clinically relevant hypotension (RR < 100/80), simultaneous application of potassium-sparing diuretics, ACE inhibitors or AT-II antagonists, NSAR, thiazide-diuretics, carbenoxolon, digoxin, neomycin, lithium. Missing capacity for consent or hospitalisation of patients against their will, insufficient knowledge of the German language, state of treatment resistance or never treated schizophrenia.

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Addresses

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    • Klinikum der Universität München, Campus Großhadern
    • Marchioninistraße 15
    • 81377  München
    • Germany
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    • Klinikum rechts der Isar der TU München
    • Ismaninger Str. 22
    • 81675  München
    • Germany
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    • Klinikum der Universität München - Klinik für Psychiatrie und Psychotherapie
    • Mr.  PD Dr  Alkomiet  Hasan 
    • Nussbaumstraße 7
    • 80366  München
    • Germany
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    • Klinikum der Universität München - Klinik für Psychiatrie und Pychotherapie
    • Mr.  PD Dr  Alkomiet  Hasan 
    • Nussbaumstraße 7
    • 80366  München
    • Germany
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Sources of Monetary or Material Support

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    • The Stanley Medical Research Institute
    • Ms.  MPH  Jana  Bowcut 
    • 8401 Connecticut Avenue, Suite 200
    • 8401  Chevy Chase, MD 20815
    • United States
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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