Agomelatine Treatment of Depression in Schizophrenia (AGOPSYCH)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2013 by Central Institute of Mental Health, Mannheim
Sponsor:
Collaborator:
Servier
Information provided by (Responsible Party):
Central Institute of Mental Health, Mannheim
ClinicalTrials.gov Identifier:
NCT01822418
First received: March 11, 2013
Last updated: March 27, 2013
Last verified: March 2013
  Purpose

Major depressive episodes (MDEs) occur frequently during the course of psychotic disorders, and several antidepressive agents have been successfully applied. The new melatonergic antidepressant agomelatine (AGO) appears promising for the treatment of MDEs in schizophrenia for several reasons. The investigators plan to test the efficacy and tolerability of AGO for antidepressive treatment in schizophrenia. For this task, the investigators plan to enrol 27 schizophrenic patients into an open, single-armed, prospective clinical trial with agomelatine.


Condition Intervention Phase
Schizophrenia
Schizophrenia-spectrum-disorders
Drug: agomelatine
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Agomelatine Treatment of Major Depressive Episodes in the Course of Schizophrenic Psychoses (AGOPSYCH)

Resource links provided by NLM:


Further study details as provided by Central Institute of Mental Health, Mannheim:

Primary Outcome Measures:
  • Antidepressive efficacy [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Comparison of MDE severity before and after six weeks of treatment with AGO. In order to assess the treatment success, means of HAM-D17 and CDSS scores at both baseline and week 6 will be compared within the efficacy sample (at least one application of AGO, LOCF). The primary endpoint will be tested with a two-sided student's t-test at a level of statistical significance of ≤.05.


Secondary Outcome Measures:
  • Secondary efficacy measures: Response rates [ Time Frame: 6 weeks and 3 months ] [ Designated as safety issue: No ]
    We will determine the percentage of responses (decrease of HAMD by at least 50 %)

  • Secondary efficacy measures: Long-term efficacy [ Time Frame: 6 weeks and 3 months ] [ Designated as safety issue: No ]
    After 12 weeks of treatment we plan to compare means of HAMD and CDSS with baseline data.

  • Secondary efficacy measures: Psychosocial functioning [ Time Frame: 6 weeks and 3 months ] [ Designated as safety issue: No ]
    During treatment psychosocial functioning might improve. We plan to compare means of PSP scale assessed after 6 weeks and 3 months with baseline data.

  • Secondary tolerability and safety measures: Psychotic symptoms [ Time Frame: 6 weeks and 3 months ] [ Designated as safety issue: Yes ]
    The stability of the psychotic syndrome during treatment with AGO will be evaluated comparing means of PANSS after 6 weeks and 3 months with baseline.

  • Secondary tolerability and safety measures: General tolerability [ Time Frame: 6 weeks and 3 months ] [ Designated as safety issue: Yes ]
    The general tolerability measures include the exploration and documentation of adverse events.

  • Secondary tolerability and safety measures: Pharmacokinetic interactions between AGO and antipsychotic agents [ Time Frame: 6 weeks and 3 months ] [ Designated as safety issue: Yes ]
    Effects of AGO treatment on serum drug levels of antipsychotic agents will be evaluated by comparing the SDLs at baseline with values obtained after 6 weeks and 3 months.

  • Secondary efficacy measures: Remission rates [ Time Frame: 6 weeks and 3 months ] [ Designated as safety issue: No ]
    We will determine the percentage of remissions (decrease of HAMD below 8)

  • Secondary efficacy measures: Cognitive functioning [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    During treatment neurocognitive deficits might improve. We plan to compare means in the MCCB assessed after 3 months with baseline data.


Estimated Enrollment: 27
Study Start Date: January 2013
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment
Open-label treatment with agomelatine 25 mg/day (or 50 mg/day after week 3).
Drug: agomelatine
n.a.
Other Name: Valdoxan

Detailed Description:

Major depressive episodes (MDEs) occur frequently during the course of psychotic disorders, and several antidepressive agents have been successfully applied. The new melatonergic antidepressant agomelatine (AGO) appears promising for the treatment of MDEs in schizophrenia for several reasons: 1. AGO provides a unique pharmacological profile by combining antidepressive potency, sleep regulation and enhancement of frontocortical dopaminergic activity by 5-HT-2C-blockade. 2. AGO might exert favourable effects on cognition. 3. While pharmacokinetic interactions are generally possible, major influences on antipsychotic substances are unlikely due to metabolism by cytochrome isoenzymes CYP1A2 and CYP2C9/19. 4. AGO is characterized by a favourable range of adverse events (AE) which do not overlap with typical antipsychotic AEs such as weight gain and sexual dysfunction. Thus, the risk of additive effects seems to be small. The investigators plan to enroll 27 schizophrenic patients into an open, single-armed, prospective clinical trial with agomelatine. As predefined primary and secondary endpoints, we are going to investigate whether AGO is able to improve MDE severity, sleep quality, general and psychosocial functioning as well as cognitive function in schizophrenia without detrimental effects on the psychotic syndrome. Moreover, we intend to monitor for pharmacokinetic interactions. The results obtained will allow designing future randomized and controlled clinical trials in order to improve the range of therapeutic options for affective and cognitive deficits in schizophrenia.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age between 18 and 60 years.
  2. Presence of an MDE according to ICD-10 criteria (HAMD17 ≥ 18 or CDSS-Score ≥ 8 points).
  3. Lifetime diagnosis of schizophrenia-spectrum disorder according to ICD-10 (F 20, F22, F23, F25).
  4. Partial remission of psychotic positive symptoms (PANSS positive subscore ≤ 15 points).
  5. Stable antipsychotic medication for at least 2 weeks (tolerable quantitative changes of daily dosage ≤ 25%).
  6. The patient is able to give an informed consent. In case of legal guardianship, the custodian will have to agree to the patient's participation.

Exclusion Criteria:

  1. Contraindications against AGO treatment
  2. Insufficient contraception in women of childbearing potential when sexually active.
  3. Gravidity or breastfeeding.
  4. Addiction to alcohol
  5. Current abuse of THC and other illegal substances according to ICD-10
  6. Dementia
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01822418

Contacts
Contact: Mathias Zink, MD ++49 621 1703 ext 2911 mathias.zink@zi-mannheim.de
Contact: Susanne Englisch, MD ++49 621 1703 ext 2521 susanne.englisch@zi-mannheim.de

Locations
Germany
Central Institute of Mental Health Recruiting
Mannheim, Baden-Württemberg, Germany, 68159
Contact: Mathias Zink, MD    ++49 621 1703 ext 2911    mathias.zink@zi-mannheim.de   
Contact: Susanne Englisch, MD    ++49 621 1703 ext 2521    susanne.englisch@zi-mannheim.de   
Principal Investigator: Mathias Zink, MD         
Sub-Investigator: Susanne Englisch, MD         
Sub-Investigator: Antje Lewien, MD         
Sponsors and Collaborators
Central Institute of Mental Health, Mannheim
Servier
Investigators
Principal Investigator: Mathias Zink, MD Central Institute of Mental Health, Department of Psychiatry and Psychotherapy
  More Information

No publications provided

Responsible Party: Central Institute of Mental Health, Mannheim
ClinicalTrials.gov Identifier: NCT01822418     History of Changes
Other Study ID Numbers: 01112012
Study First Received: March 11, 2013
Last Updated: March 27, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Central Institute of Mental Health, Mannheim:
Schizophrenia
Depression
Cognition
Agomelatine
Antidepressant

Additional relevant MeSH terms:
Schizophrenia
Mental Disorders
Schizophrenia and Disorders with Psychotic Features
S 20098
Central Nervous System Agents
Central Nervous System Depressants
Hypnotics and Sedatives
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014