Bipolar DisorderNCT01552837
Effects of Quetiapine on Ultrastructural Hippocampal and Neurochemical Changes in Patients With Bipolar Disorder: Searching for Antidepressant and Mood Stabilising Neurophysiology
A study testing Seroquel in people with Bipolar Disorder, run by RWTH Aachen University at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Bipolar Disorder
- What is being tested?
- Seroquel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 1 siteGermany
- Study dates
- Dec 2007to Dec 2010
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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,
Show all 10Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Germany1 site
Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital Aachen
Aachen, 52074
About this study
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.
Read the 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.
- Conditions
- Bipolar Disorder
- Being tested
- Seroquel
- Keywords
- Diffusion Tensor Imaging,, quetiapine, Bipolar Disorder, hippocampus, Volume Brain Morphometry, Magnetic Resonance Spectroscopy, effect of quetiapine on hippocampal neurogenesis
- Medical subject headings
- Bipolar Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SeroquelDrug
for 4 weeks, 300 - 800 mg per day in 2 doses
| Study group | Role | What they receive |
|---|---|---|
| Healthy volunteers | No intervention | MRI compatible, no present or past DSM-IV diagnosis |
| patients with Bipolar Disorder | Active comparator | MRI compatible, presence of DSM-IV diagnosis for Bipolar Disorder Receives: Drug: Seroquel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Anisotropy in hippocampal formation detected with Diffusion Tensor Imaging (DTI)
Detection of pharmacologically induced equivalents of neurogenesis and synaptic sprouting in the hippocampal region.
Measured: after 6 weeks
Secondary outcomes (5)
safety and tolerability of medical treatment
Observation of adverse events and tolerability assessed by vital signs and clinical chemistry
Measured: every time during the study
Detection of pharmacologically induced localised volume changes
Measurement with 3D MPRAGE (structural scan)
Measured: after 6 weeks
Detection of pharmacologically induced localised changes in water content
differentiation between neurogenesis/sprouting and mere water intake
Measured: after 6 weeks
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
Measured: after 6 weeks
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
Measured: after 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2012 (estimated)
- Study startDec 2007
- Primary completionFeb 2010
- Study completionDec 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Bipolar DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- RWTH Aachen University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Klaus Mathiak, Prof MD, Study director, Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital Aachen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01552837
- Sponsor's protocol ID
- D1449L00030
- Other IDs
- 2007-000479-40, EK 024/07, 07-010
- Status last verified
- Mar 2012
- First submitted
- 2 Mar 2012
- Last updated
- 13 Mar 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 8019776Luo 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.
PubMed 16271709Vieta 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.
PubMed 15880391
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Quetiapine on Ultrastructural Hippocampal and Neurochemical Changes in Patients With Bipolar Disorder: Searching for Antidepressant and Mood Stabilising Neurophysiology
- ClinicalTrials.gov ID
- NCT01552837
- Acronym / sponsor ID
- D1449L00030
- Conditions
- Bipolar Disorder
- Keywords
- Diffusion Tensor Imaging,, quetiapine, Bipolar Disorder, hippocampus, Volume Brain Morphometry, Magnetic Resonance Spectroscopy, effect of quetiapine on hippocampal neurogenesis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- RWTH Aachen UniversityUniversity, hospital or other
- Study start
- Dec 2007
- Primary completion
- Feb 2010 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 13 Mar 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Healthy volunteers | No intervention | –MRI compatible, no present or past DSM-IV diagnosis |
| patients with Bipolar Disorder | Active comparator | Drug: SeroquelMRI compatible, presence of DSM-IV diagnosis for Bipolar Disorder |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (10 listed)
- 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,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Seroquelfor 4 weeks, 300 - 800 mg per day in 2 doses | Drug | patients with Bipolar Disorder |
Primary outcome
Anisotropy in hippocampal formation detected with Diffusion Tensor Imaging (DTI)
Time frame: after 6 weeks
Detection of pharmacologically induced equivalents of neurogenesis and synaptic sprouting in the hippocampal region.
5 secondary outcomes
safety and tolerability of medical treatment
Time frame: every time during the study
Detection of pharmacologically induced localised volume changes
Time frame: after 6 weeks
Detection of pharmacologically induced localised changes in water content
Time frame: after 6 weeks
Detection of pharmacologically induced neurochemical changes in the medial temporal regions (Glx and NAA, choline)
Time frame: after 6 weeks
Detection of pharmacologically induced differential activation during an episodic memory task measured with fMRI.
Time frame: after 6 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2012.
- Background: PubMed 8019776Basser 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.
- Background: PubMed 16271709Luo 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.
- Background: PubMed 15880391Vieta 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Klaus Mathiak, Prof MD study director
Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital Aachen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Seroquel in people with Bipolar Disorder, run by RWTH Aachen University at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Mar 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Anisotropy in hippocampal formation detected with Diffusion Tensor Imaging (DTI) (time frame: after 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01552837, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Mar 2012.