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Effect of Quetiapine on Brain Activity Patterns in Patients With Heightened Risk of Bipolar Disorder

Primary Purpose

Depression, Bipolar Disorder

Status
Unknown status
Phase
Not Applicable
Locations
Germany
Study Type
Interventional
Intervention
Quetiapine
Placebo
Sponsored by
RWTH Aachen University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Depression

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • diagnosis of depressive episode (F32.X, F33.X) with duration less than < 6 months
  • max. three previous episodes of illness
  • no manic or hypomanic episodes in the past
  • current treatment with one antidepressant
  • MRI-compatibility
  • unequivocal understanding of study information and autonomous consent
  • for women: negative pregnancy test

  • for risk-group:

    • 14 or more points on hypomania checklist (HCL-32)

    • additionally at least one of the following four risk factors:

      1. positive family history (i.e. first or second order relatives with BPD, schizoaffective or schizophrenic psychosis, mania or suicide attempt)
      2. initial manifestation before 30 years of age
      3. initial manifestation after childbirth
      4. suicide attempt in the past

Exclusion Criteria:

  • additional diagnoses of psychiatric disorders (Organic, including symptomatic, mental disorders [F0X.X]; mental and behavioural disorders due to psychoactive substance use [F1X.X]; schizophrenia, schizotypal and delusional disorders [F2X.X]; mental retardation [F7X.X])
  • chronic or acute physical disease
  • individuals who are in a dependence- or work-relation with the sponsor
  • limited or annulled legal capacity
  • court or administrative order for hospitalisation
  • for women: pregnancy, nursing period or unsafe contraceptive methods

  • for the risk group:

    • clinical relevant changes in clinical chemistry, hematology, EEG or EKG
    • known contraindication for quetiapine (e.g. hypersensitivity to [active] ingredient[s], HIV-protease inhibitors, antimycotics, antibiotics)

Sites / Locations

  • Clinic for psychiatry, psychotherapy and psychosomatic, RWTH Aachen University Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

No Intervention

Arm Label

Quetiapine

Placebo

Control-group

Arm Description

18 patients of the risk-group will receive quetiapine (Seroquel Prolong (c)) for 8 weeks in adjunction to their antidepressant standard therapy. Group allocation is randomised and double-blind. Dosages: 50mg (day 1-3), 100mg (day 4-6) and 150mg (from day 7 onwards). Administration: Quetiapine will be given once daily before bedtime, not together with a meal and swallowed as a whole.

18 patients of the risk-group will receive placebo for 8 weeks in adjunction to their antidepressant standard therapy. Group allocation is randomised and double-blind. The placebo does not contain any psychoactive substance.

18 depressive patients without a heightened risk for BPD will not receive any medication apart from their standard antidepressant therapy (control-group).

Outcomes

Primary Outcome Measures

BOLD signal during a combined inhibition-reward-task
At baseline (day 0) the risk-group and control-group will be compared on BOLD signal (and behavioural data) during a combined inhibition-reward-task (neuronal correlate of cognitive control) (fMRI). These measures will be obtained once again at visit 4 (day 56) in the risk-group to evaluate the impact of quetiapine (i.e. change from baseline measure).
Functional connectivity in the default mode network during resting state (rstfMRI)
At baseline (day 0) the risk-group and control-group will be compared on functional connectivity in the default mode network during resting state (rstfMRI).
Structural differences in brain anatomy (MRI)
At baseline (day 0) the risk-group and control-group will be compared on structural differences in brain anatomy (MRI).
Structural integrity of nerve fibres (DTI)
At baseline (day 0) the risk-group and control-group will be compared on structural integrity of nerve fibres (DTI).
Effect of quetiapine on brain measures
After the quetiapine/ placebo intervention the risk-group will be compared whether there are changes from baseline in outcome measures 1 to 4.

Secondary Outcome Measures

Plasma levels of quetiapine
Blood samples of the patients of the risk group will be obtained to analyse the plasma levels of quetiapine.
Change over time in affect and psychopathology
All patients (risk-group and control group) will be assessed with questionnaires tapping affect and psychopathology (MADRS, YMRS, CGI, PANSS, BDI-II, Bf-S, SWN-K, EPS, BARS, C-SSRS, NGASR). These measures will be obtained at three different time points to evaluate the respective change over time.
Personality
All patients (risk-group and control group) will be assessed with questionnaires of personality (TCI-R, BIS-15, RS-13).

Full Information

First Posted
April 22, 2015
Last Updated
May 18, 2015
Sponsor
RWTH Aachen University
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1. Study Identification

Unique Protocol Identification Number
NCT02451306
Brief Title
Effect of Quetiapine on Brain Activity Patterns in Patients With Heightened Risk of Bipolar Disorder
Official Title
Cognitive Control and Functional Connectivity During Resting State in Patients With Heightened Risk of Bipolar Disorder - a Quetiapine Challenge
Study Type
Interventional

2. Study Status

Record Verification Date
May 2015
Overall Recruitment Status
Unknown status
Study Start Date
June 2015 (undefined)
Primary Completion Date
May 2017 (Anticipated)
Study Completion Date
May 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
RWTH Aachen University

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Bipolar disorder (BPD) is often misdiagnosed as unipolar depression. This leads to inadequate treatment and can have negative impact on the course of the disease. There is now preliminary evidence that patients with unipolar and bipolar depression as well as healthy individuals with a heightened risk of BPD can be distinguished from each other based on their brain activity patterns and functional connectivity during resting state. However, the impact of pharmacological treatment on these functional brain measures have not yet been clarified. For common antidepressants it has been shown that they seem to normalise aberrant brain activity patterns and functional connectivity. The problem is that some antidepressants can induce mania or accelerate pathological cycling in depressive patients with unrecognised BPD. Therefore, pharmacological drugs with mood-stabilising properties such as quetiapine are more and more prescribed. Although the effectiveness and tolerability have been proven, the neuronal effects of these adjunctive treatments are not clear. The aim of the study is thus to investigate the impact of quetiapine on measures of brain activity in depressive patients with a heightened risk of BPD. Moreover, the investigators want to examine whether the investigators can distinguish depressive patients with a heightened risk of BPD from depressive patients without a heightened risk of BPD using neuroimaging techniques, and whether these measures can predict the course of the disease.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Depression, Bipolar Disorder

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
54 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Quetiapine
Arm Type
Experimental
Arm Description
18 patients of the risk-group will receive quetiapine (Seroquel Prolong (c)) for 8 weeks in adjunction to their antidepressant standard therapy. Group allocation is randomised and double-blind. Dosages: 50mg (day 1-3), 100mg (day 4-6) and 150mg (from day 7 onwards). Administration: Quetiapine will be given once daily before bedtime, not together with a meal and swallowed as a whole.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
18 patients of the risk-group will receive placebo for 8 weeks in adjunction to their antidepressant standard therapy. Group allocation is randomised and double-blind. The placebo does not contain any psychoactive substance.
Arm Title
Control-group
Arm Type
No Intervention
Arm Description
18 depressive patients without a heightened risk for BPD will not receive any medication apart from their standard antidepressant therapy (control-group).
Intervention Type
Drug
Intervention Name(s)
Quetiapine
Other Intervention Name(s)
Seroquel Prolong
Intervention Description
See information in arm description.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
See information in arm description.
Primary Outcome Measure Information:
Title
BOLD signal during a combined inhibition-reward-task
Description
At baseline (day 0) the risk-group and control-group will be compared on BOLD signal (and behavioural data) during a combined inhibition-reward-task (neuronal correlate of cognitive control) (fMRI). These measures will be obtained once again at visit 4 (day 56) in the risk-group to evaluate the impact of quetiapine (i.e. change from baseline measure).
Time Frame
Baseline (Day 0)
Title
Functional connectivity in the default mode network during resting state (rstfMRI)
Description
At baseline (day 0) the risk-group and control-group will be compared on functional connectivity in the default mode network during resting state (rstfMRI).
Time Frame
Baseline (Day 0)
Title
Structural differences in brain anatomy (MRI)
Description
At baseline (day 0) the risk-group and control-group will be compared on structural differences in brain anatomy (MRI).
Time Frame
Baseline (Day 0)
Title
Structural integrity of nerve fibres (DTI)
Description
At baseline (day 0) the risk-group and control-group will be compared on structural integrity of nerve fibres (DTI).
Time Frame
Baseline (Day 0)
Title
Effect of quetiapine on brain measures
Description
After the quetiapine/ placebo intervention the risk-group will be compared whether there are changes from baseline in outcome measures 1 to 4.
Time Frame
Visit 4 (Day 56)
Secondary Outcome Measure Information:
Title
Plasma levels of quetiapine
Description
Blood samples of the patients of the risk group will be obtained to analyse the plasma levels of quetiapine.
Time Frame
Visit 4 (Day 56)
Title
Change over time in affect and psychopathology
Description
All patients (risk-group and control group) will be assessed with questionnaires tapping affect and psychopathology (MADRS, YMRS, CGI, PANSS, BDI-II, Bf-S, SWN-K, EPS, BARS, C-SSRS, NGASR). These measures will be obtained at three different time points to evaluate the respective change over time.
Time Frame
Baseline (Day 0), Visit 4 (Day 56), Follow-up (after 1 year)
Title
Personality
Description
All patients (risk-group and control group) will be assessed with questionnaires of personality (TCI-R, BIS-15, RS-13).
Time Frame
Baseline (Day 0)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: diagnosis of depressive episode (F32.X, F33.X) with duration less than < 6 months max. three previous episodes of illness no manic or hypomanic episodes in the past current treatment with one antidepressant MRI-compatibility unequivocal understanding of study information and autonomous consent for women: negative pregnancy test for risk-group: 14 or more points on hypomania checklist (HCL-32) additionally at least one of the following four risk factors: positive family history (i.e. first or second order relatives with BPD, schizoaffective or schizophrenic psychosis, mania or suicide attempt) initial manifestation before 30 years of age initial manifestation after childbirth suicide attempt in the past Exclusion Criteria: additional diagnoses of psychiatric disorders (Organic, including symptomatic, mental disorders [F0X.X]; mental and behavioural disorders due to psychoactive substance use [F1X.X]; schizophrenia, schizotypal and delusional disorders [F2X.X]; mental retardation [F7X.X]) chronic or acute physical disease individuals who are in a dependence- or work-relation with the sponsor limited or annulled legal capacity court or administrative order for hospitalisation for women: pregnancy, nursing period or unsafe contraceptive methods for the risk group: clinical relevant changes in clinical chemistry, hematology, EEG or EKG known contraindication for quetiapine (e.g. hypersensitivity to [active] ingredient[s], HIV-protease inhibitors, antimycotics, antibiotics)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lina Winkler, M.Sc.
Email
liwinkler@ukaachen.de
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Frank Schneider, Univ.-Prof.
Organizational Affiliation
University Hospital, Aachen
Official's Role
Study Director
Facility Information:
Facility Name
Clinic for psychiatry, psychotherapy and psychosomatic, RWTH Aachen University Hospital
City
Aachen
State/Province
NRW
ZIP/Postal Code
52074 Aachen
Country
Germany

12. IPD Sharing Statement

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Effect of Quetiapine on Brain Activity Patterns in Patients With Heightened Risk of Bipolar Disorder

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