Back to results

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

Primary Purpose

Bipolar Disorder

Status

Completed

Phase

Not Applicable

Locations

Germany

Study Type

Interventional

Intervention

Seroquel

About this trial

This is an interventional treatment trial for Bipolar Disorder focused on measuring Diffusion Tensor Imaging,, quetiapine, Bipolar Disorder, hippocampus, Volume Brain Morphometry, Magnetic Resonance Spectroscopy, effect of quetiapine on hippocampal neurogenesis

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital Aachen

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Active Comparator

Arm Label

Healthy volunteers

patients with Bipolar Disorder

Arm Description

MRI compatible, no present or past DSM-IV diagnosis

MRI compatible, presence of DSM-IV diagnosis for Bipolar Disorder

Outcomes

Primary Outcome Measures

Anisotropy in hippocampal formation detected with Diffusion Tensor Imaging (DTI)

Detection of pharmacologically induced equivalents of neurogenesis and synaptic sprouting in the hippocampal region.

Secondary Outcome Measures

safety and tolerability of medical treatment

Observation of adverse events and tolerability assessed by vital signs and clinical chemistry

Detection of pharmacologically induced localised volume changes

Measurement with 3D MPRAGE (structural scan)

Detection of pharmacologically induced localised changes in water content

differentiation between neurogenesis/sprouting and mere water intake

Detection of pharmacologically induced neurochemical changes in the medial temporal regions (Glx and NAA, choline)

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.

Measurement of BOLD response using fMRI during an episodic memory test

Full Information

NCT ID

NCT01552837

First Posted

March 2, 2012

Last Updated

March 9, 2012

Sponsor

RWTH Aachen University

1. Study Identification

Unique Protocol Identification Number

NCT01552837

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2012

Overall Recruitment Status

Completed

Study Start Date

December 2007 (undefined)

Primary Completion Date

February 2010 (Actual)

Study Completion Date

December 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

RWTH Aachen University

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

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

Bipolar Disorder

Keywords

Diffusion Tensor Imaging,, quetiapine, Bipolar Disorder, hippocampus, Volume Brain Morphometry, Magnetic Resonance Spectroscopy, effect of quetiapine on hippocampal neurogenesis

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

33 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Healthy volunteers

Arm Type

No Intervention

Arm Description

MRI compatible, no present or past DSM-IV diagnosis

Arm Title

patients with Bipolar Disorder

Arm Type

Active Comparator

Arm Description

MRI compatible, presence of DSM-IV diagnosis for Bipolar Disorder

Intervention Type

Drug

Intervention Name(s)

Seroquel

Intervention Description

for 4 weeks, 300 - 800 mg per day in 2 doses

Primary Outcome Measure Information:

Title

Anisotropy in hippocampal formation detected with Diffusion Tensor Imaging (DTI)

Description

Detection of pharmacologically induced equivalents of neurogenesis and synaptic sprouting in the hippocampal region.

Time Frame

after 6 weeks

Secondary Outcome Measure Information:

Title

safety and tolerability of medical treatment

Description

Observation of adverse events and tolerability assessed by vital signs and clinical chemistry

Time Frame

every time during the study

Title

Detection of pharmacologically induced localised volume changes

Description

Measurement with 3D MPRAGE (structural scan)

Time Frame

after 6 weeks

Title

Detection of pharmacologically induced localised changes in water content

Description

differentiation between neurogenesis/sprouting and mere water intake

Time Frame

after 6 weeks

Title

Detection of pharmacologically induced neurochemical changes in the medial temporal regions (Glx and NAA, choline)

Description

Measurement of glutamate and N-acetylaspartate in the medial temporal lobe with MRS

Time Frame

after 6 weeks

Title

Detection of pharmacologically induced differential activation during an episodic memory task measured with fMRI.

Description

Measurement of BOLD response using fMRI during an episodic memory test

Time Frame

after 6 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Klaus Mathiak, Prof MD

Organizational Affiliation

Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital Aachen

Official's Role

Study Director

Facility Information:

Facility Name

Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital Aachen

City

Aachen

ZIP/Postal Code

52074

Country

Germany

12. IPD Sharing Statement

Citations:

PubMed Identifier

8019776

Citation

Basser PJ, Mattiello J, LeBihan D. Estimation of the effective self-diffusion tensor from the NMR spin echo. J Magn Reson B. 1994 Mar;103(3):247-54. doi: 10.1006/jmrb.1994.1037.

Results Reference

background

PubMed Identifier

16271709

Citation

Luo C, Xu H, Li XM. Quetiapine reverses the suppression of hippocampal neurogenesis caused by repeated restraint stress. Brain Res. 2005 Nov 23;1063(1):32-9. doi: 10.1016/j.brainres.2005.09.043. Epub 2005 Nov 4.

Results Reference

background

PubMed Identifier

15880391

Citation

Vieta E. Mood stabilization in the treatment of bipolar disorder: focus on quetiapine. Hum Psychopharmacol. 2005 Jun;20(4):225-36. doi: 10.1002/hup.689. Erratum In: Hum Psychopharmacol. 2005 Jul;20(5):375.

Results Reference

background

Learn more about this trial

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

We'll reach out to this number within 24 hrs