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

Depression Clinical Trial

Official title:

Cognitive Control and Functional Connectivity During Resting State in Patients With Heightened Risk of Bipolar Disorder - a Quetiapine Challenge

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02451306
• Other study ID #: EK018/15
• Status: Not yet recruiting
• Phase: N/A
• First received: April 22, 2015
• Last updated: May 18, 2015
• Start date: June 2015
• Est. completion date: May 2018

Study information

• Verified date: May 2015
• Source: RWTH Aachen University
• Contact: Lina Winkler, M.Sc.
• Email: liwinkler[@]ukaachen.de
• Is FDA regulated: No
• Health authority: Germany: Ethics Commission
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 54
• Est. completion date: May 2018
• Est. primary completion date: May 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 45 Years

Eligibility

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)

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Bipolar Disorder
• Depression

Intervention

Drug:
• Quetiapine
See information in arm description.
• Placebo
See information in arm description.

Locations

Country	Name	City	State
Germany	Clinic for psychiatry, psychotherapy and psychosomatic, RWTH Aachen University Hospital	Aachen	NRW

Sponsors (1)

Lead Sponsor	Collaborator
RWTH Aachen University

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	Baseline (Day 0)	No
Primary	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).	Baseline (Day 0)	No
Primary	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).	Baseline (Day 0)	No
Primary	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).	Baseline (Day 0)	No
Primary	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.	Visit 4 (Day 56)	No
Secondary	Plasma levels of quetiapine	Blood samples of the patients of the risk group will be obtained to analyse the plasma levels of quetiapine.	Visit 4 (Day 56)	No
Secondary	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.	Baseline (Day 0), Visit 4 (Day 56), Follow-up (after 1 year)	No
Secondary	Personality	All patients (risk-group and control group) will be assessed with questionnaires of personality (TCI-R, BIS-15, RS-13).	Baseline (Day 0)	No