Effects of Quetiapine on Ultrastructural Hippocampal and Neurochemical Changes in Patients With Bipolar Disorder: Searching for Antidepressant and Mood Stabilising Neurophysiology

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
RWTH Aachen University
ClinicalTrials.gov Identifier:
NCT01552837
First received: March 2, 2012
Last updated: March 9, 2012
Last verified: March 2012
  Purpose

The aim of the study was to determine the pharmacological induced equivalents of neurogenesis and synaptic sprouting in the hippocampus, localized volume changes, changes in water content and neurochemical changes in the medial temporal regions.


Condition Intervention
Bipolar Disorder
Drug: Seroquel

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effects of Quetiapine on Ultrastructural Hippocampal and Neurochemical Changes in Patients With Bipolar Disorder: Searching for Antidepressant and Mood Stabilising Neurophysiology

Resource links provided by NLM:


Further study details as provided by RWTH Aachen University:

Primary Outcome Measures:
  • Anisotropy in hippocampal formation detected with Diffusion Tensor Imaging (DTI) [ Time Frame: after 6 weeks ] [ Designated as safety issue: No ]
    Detection of pharmacologically induced equivalents of neurogenesis and synaptic sprouting in the hippocampal region.


Secondary Outcome Measures:
  • safety and tolerability of medical treatment [ Time Frame: every time during the study ] [ Designated as safety issue: Yes ]
    Observation of adverse events and tolerability assessed by vital signs and clinical chemistry

  • Detection of pharmacologically induced localised volume changes [ Time Frame: after 6 weeks ] [ Designated as safety issue: No ]
    Measurement with 3D MPRAGE (structural scan)

  • Detection of pharmacologically induced localised changes in water content [ Time Frame: after 6 weeks ] [ Designated as safety issue: No ]
    differentiation between neurogenesis/sprouting and mere water intake

  • Detection of pharmacologically induced neurochemical changes in the medial temporal regions (Glx and NAA, choline) [ Time Frame: after 6 weeks ] [ Designated as safety issue: No ]
    Measurement of glutamate and N-acetylaspartate in the medial temporal lobe with MRS

  • Detection of pharmacologically induced differential activation during an episodic memory task measured with fMRI. [ Time Frame: after 6 weeks ] [ Designated as safety issue: No ]
    Measurement of BOLD response using fMRI during an episodic memory test


Enrollment: 33
Study Start Date: December 2007
Study Completion Date: December 2010
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Healthy volunteers
MRI compatible, no present or past DSM-IV diagnosis
Active Comparator: patients with Bipolar Disorder
MRI compatible, presence of DSM-IV diagnosis for Bipolar Disorder
Drug: Seroquel
for 4 weeks, 300 - 800 mg per day in 2 doses

Detailed Description:

Quetiapine is an antipsychotic that has mood stabilizing and antidepressant effects (Vieta, 2005). Animal studies showed that the expression of neurotrophins and the subsequent modulation of the neuroplastic processes, including neurogenesis in the hippocampus, play a key role in the mechanism of mood stabilizing (Kim et al., 2004) and antidepressant (Santarelli et al., 2003). Since atypical antipsychotics also have antidepressant and mood stabilizing effect, it is hypothesized that the common mechanism of action in all three pharmacological classes is neurogenesis and synaptic sprouting in the hippocampal region. Thus, the aim of this study was to test this hypothesis.

Quetiapine was associated with antidepressant and mood stabilizing effects in patients with bipolar disorder (Vieta, 2005). The evidence based on animal studies shows that administration of quetiapine attenuates the decrease in levels of brain-derived neurotrophic factor in the hippocampi. This may explain the improved cognitive symptoms in patients with schizophrenia and depression (Luo et al., 2005, Park et al, 2006).

The aim of the study was to determine the pharmacological induced equivalents of neurogenesis and synaptic sprouting in the hippocampus, localized volume changes, changes in water content and neurochemical changes in the medial temporal regions.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • age ranging 18 - 55 years old
  • intelligence coefficient (IQ) of minimum 85 as estimated by MWT-B
  • MRI compatibility
  • for healthy volunteers - no DSM-IV diagnosis
  • patients should have had a diagnosis of bipolar disorder in accordance with DSM-IV.

Exclusion Criteria:

  • substances or alcohol abuse or dependence (except caffeine and nicotine) at enrollment;
  • medical conditions that would affect absorption, distribution, metabolism or excretion of study treatment;
  • unstable or inadequately treated medical illness (diabetes, angina, pectoris, hypertension);
  • diabetes mellitus
  • patients who in the opinion of the investigator pose a risk of suicide or danger to self or others,
  • patients who known intolerance or lack of response to Quetiapine fumarate,
  • patients who use of any of the cytochrome P450 3A4 inhibitors (ketoconazole, itraconazole, nelfinavir, ritonavir, fluvoxamine and saquinavir) in the 14 days preceding enrollment,
  • patients who use of any of the cytochrome P450 inducers (phenytoin, carbamazepine, barbiturates, rifampin, St. John's Wort and glucocorticoids) in the 14 days preceding enrollment,
  • current treatment of Quetiapine or use of mood stabilizer or antidepressant as co-medication throughout the study.
  • lack of inform consent
  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: NCT01552837

Locations
Germany
Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital Aachen
Aachen, Germany, 52074
Sponsors and Collaborators
RWTH Aachen University
Investigators
Study Director: Klaus Mathiak, Prof MD Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital Aachen
  More Information

Publications:
Responsible Party: RWTH Aachen University
ClinicalTrials.gov Identifier: NCT01552837     History of Changes
Other Study ID Numbers: D1449L00030, 2007-000479-40, EK 024/07, 07-010
Study First Received: March 2, 2012
Last Updated: March 9, 2012
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by RWTH Aachen University:
Diffusion Tensor Imaging,
quetiapine
Bipolar Disorder
hippocampus
Volume Brain Morphometry
Magnetic Resonance Spectroscopy
effect of quetiapine on hippocampal neurogenesis

Additional relevant MeSH terms:
Bipolar Disorder
Affective Disorders, Psychotic
Mood Disorders
Mental Disorders
Antidepressive Agents
Quetiapine
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 24, 2014