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

NCT02451306 | Unknown

• 1 other identifier: EK018/15
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

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.

Conditions

Depression; Bipolar Disorder

Outcome Measures

Primary Outcomes (5)

• 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)

• 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)

• 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)

• 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)

• 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)

Secondary Outcomes (3)

• Plasma levels of quetiapine

  Visit 4 (Day 56)

• Change over time in affect and psychopathology

  Baseline (Day 0), Visit 4 (Day 56), Follow-up (after 1 year)

• Personality

  Baseline (Day 0)

Study Arms (3)

Quetiapine

EXPERIMENTAL

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.

Drug: Quetiapine

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Control-group

NO INTERVENTION

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

Interventions

Quetiapine DRUG

See information in arm description.

Also known as: Seroquel Prolong

Quetiapine

Placebo DRUG

See information in arm description.

Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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:
• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• RWTH Aachen University: lead

Study Sites (1)

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

Aachen, North Rhine-Westphalia, 52074 Aachen, Germany

Location

MeSH Terms

Conditions

Depression; Bipolar Disorder

Interventions

Quetiapine Fumarate

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Bipolar and Related Disorders; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Dibenzothiazepines; Thiazepines; Thiepins; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Frank Schneider, Univ.-Prof.

  University Hospital, Aachen

  STUDY DIRECTOR

Central Study Contacts

Lina Winkler, M.Sc.

CONTACT

liwinkler@ukaachen.de

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2015
• First Posted: May 21, 2015
• Study Start: June 1, 2015
• Primary Completion: May 1, 2017
• Study Completion: May 1, 2018
• Last Updated: May 21, 2015

Record last verified: 2015-05

Locations

DE (1)