Major DepressionPhase 3NCT00953108
Quetiapine Prolong, Escitalopram and Hypothalamic-pituitary-adrenocortical (HPA) Axis Activity in Depressed Patients
A Phase 3 study testing quetiapine and escitalopram in people with Major Depression, run by Ludwig-Maximilians - University of Munich at 1 site in Germany.
Trial summary
In former studies of the investigators research group the investigators could also demonstrate acute inhibitory effects of the antidepressant mirtazapine on ACTH and cortisol release in normal controls (Schüle et al. 2002), most likely mediated via antagonism at central 5-HT2- and H1-receptors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Major Depression
- What is being tested?
- quetiapine and escitalopram
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteGermany
- Study dates
- Sep 2009to Feb 2012
- Phase
- Phase 3
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- For inclusion in the study patients must fulfil all of the following criteria:
- Inpatients (the admission to hospital occurs independently from study participation)
- Provision of written informed consent
- A diagnosis of major depression by Diagnostic and Statistical Manual of Mental Disorders- Fourth Edition (DSM-IV) (unipolar depression: 296.2, 296.3)
- Female and male patients aged 18 to 65 years
- Female patients of childbearing potential must have a negative serum human chorionic gonadotropin (hCG) pregnancy test at enrolment and e willing to use a reliable method of birth control (i.e. barrier method, oral contraceptive, implant, dermal contraception, long-term injectable contraceptive, intrauterine device, or tubal litigation) during the study.
- Able to understand and comply with the requirements of the study as judged by the investigator.
- A sum score of at least 18 on the 21-item version of the Hamilton Depression Rating Scale (21-HAMD)
Who cannot join
- Any of the following is regarded as a criterion for exclusion from the study:
- Pregnancy or lactation
- Any DSM-IV Axis I disorder not defined in the inclusion criteria
- Patients who, in the opinion of the investigator, pose an imminent risk of suicide or a danger to self or others
- Known intolerance or lack of response to quetiapine fumarate and/or escitalopram, as judged by the investigator
- Use of any of the following cytochrome P450 3A4 inhibitors in the 14 days preceding enrolment including but not limited to: ketoconazole, itraconazole, fluconazole, erythromycin, clarithromycin, troleandomycin, indinavir, nelfinavir, ritonavir, fluvoxamine and saquinavir
Show all 31Show fewer
- Use of any of the following cytochrome P450 3A4 inducers in the 14 days preceding enrolment including but not limited to: phenytoin, carbamazepine, barbiturates, rifampin, St. John's Wort, and glucocorticoids
- Use of monoamine oxidase inhibitors (MAOIs) or other serotonergic drugs (e.g. triptans) in the 14 days preceding enrolment
- Use of oral anticoagulants in the 14 days preceding enrolment
- History of bleeding disorders.
- Use of drugs which are mainly metabolized by cytochrome P450 2D6 having a low therapeutic index (e.g. flecainide, propafenone, metoprolol) in the 14 days preceding enrolment
- Administration of a depot antipsychotic injection within one dosing interval (for the depot) before randomisation
- Substance or alcohol dependence at enrolment (except dependence in full remission, and except for caffeine or nicotine dependence), as defined by DSM-IV criteria
- Opiates, amphetamine, barbiturate, cocaine, cannabis, or hallucinogen abuse by DSM-IV criteria within 4 weeks prior to enrolment
- Medical conditions that would affect absorption, distribution, metabolism, or excretion of study treatment
- Unstable or inadequately treated medical illness (e.g. congestive heart failure, angina pectoris, hypertension) as judged by the investigator
- Involvement in the planning and conduct of the study
- Previous enrolment or randomisation of treatment in the present study.
- Participation in another drug trial within 4 weeks prior enrolment into this study or longer in accordance with local requirements
- A patient with Diabetes Mellitus (DM) fulfilling one of the following criteria:
- Unstable DM defined as enrolment glycosylated hemoglobin (HbA1c) >8.5%.
- Admitted to hospital for treatment of DM or DM related illness in past 12 weeks.
- Not under physician care for DM
- Physician responsible for patient's DM care has not indicated that patient's DM is controlled.
- Physician responsible for patient's DM care has not approved patient's participation in the study
- Has not been on the same dose of oral hypoglycaemic drug(s) and/or diet for the 4 weeks prior to randomisation. For thiazolidinediones (glitazones) this period should not be less than 8 Weeks.
- Taking insulin whose daily dose on one occasion in the past 4 weeks has been more than 10% above or below their mean dose in the preceding 4 weeks Note: If a diabetic patient meets one of these criteria, the patient is to be excluded even if the treating physician believes that the patient is stable and can participate in the study.
- An absolute neutrophil count (ANC) of 1.5 x 109 per liter
- Abnormal laboratory parameters of clinical relevance before enrolment
- Abnormal blood pressure, abnormal electrocardiogram, and/or abnormal electroencephalogram with clinical relevance before enrolment
- Psychotropic drugs within 3 days before and throughout the study with the exception of zopiclon (up to 7.5 mg per day) in case of sleep difficulties and lorazepam (up to 2 mg per day) in case of inner tension and anxiety
Trial locations and contacts
1 site in 1 country.
Germany1 site
Department of Psychiatry, Ludwig-Maximilian-University
Munich, Bavaria, 80336
About this study
Official title: Impact of Quetiapine Prolong and Escitalopram on the Hypothalamic-pituitary-adrenocortical (HPA)-Axis Activity in Depressed Patients
In former studies of the investigators research group the investigators could also demonstrate acute inhibitory effects of the antidepressant mirtazapine on ACTH and cortisol release in normal controls (Schüle et al. 2002), most likely mediated via antagonism at central 5-HT2- and H1-receptors. In contrast to mirtazapine, serotonin or norepinephrine reuptake inhibiting antidepressants acutely stimulate ACTH and cortisol secretion (Schüle 2007). The investigators also performed a study in depressed patients who were treated either with mirtazapine or with reboxetine using serial dexamethasone/CRH tests (week 0, 1, and 5) as a parameter for HPA axis activity. Mirtazapine, but not the norepinephrine reuptake inhibitor reboxetine was able to significantly reduce HPA axis activity already within one week (Schüle et al. 2006). Mirtazapine is known to have an earlier onset of antidepressant action than do SSRIs such as sertraline (Behnke et al. 2003) or antidepressants with dual mechanism of action such as venlafaxine (Benkert et al. 2006), possibly due to its rapid inhibition of HPA axis activity in unipolar depressed patients.
Since mirtazapine and quetiapine have similar effects on the HPA system in healthy male volunteers (i.e. inhibition of ACTH and cortisol secretion), a rapid attenuation of HPA axis activity is also expected during quetiapine XR treatment in depressed patients.
Therefore, in the present study the investigators goal is to investigate whether quetiapine fumarate XR at a dosage of 300 mg per day has an impact on HPA axis activity in unipolar depressed patients, as measured by serial dexamethasone/CRH tests (week 0, 1, and 5) and salivary cortisol profiles and whether putative effects of quetiapine XR on the HPA system are related to its antidepressant efficacy.
- Conditions
- Major Depression
- Being tested
- quetiapine, escitalopram
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
quetiapineDrug
300 mg per day
escitalopramDrug
escitalopram 10 mg per day
| Study group | Role | What they receive |
|---|---|---|
| quetiapine | Experimental | Not described Receives: Drug: quetiapine |
| escitalopram | Active comparator | Not described Receives: Drug: escitalopram |
What is being measured
The primary outcome is the main question the study is designed to answer.
serial dexamethasone/CRH tests
Measured: week 0, 1, and 5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2009 (estimated)
- Study startSep 2009
- Primary completionFeb 2012
- Study completionFeb 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Major DepressionStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ludwig-Maximilians - University of Munich
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Cornelius.Schuele, Ludwig-Maximilians - University of Munich
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00953108
- Sponsor's protocol ID
- QUE/09
- Status last verified
- Feb 2013
- First submitted
- 5 Aug 2009
- Last updated
- 12 Feb 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
Sarubin N, Nothdurfter C, Schmotz C, Wimmer AM, Trummer J, Lieb M, Uhr M, Baghai TC, Wetter TC, Buhner M, Rupprecht R, Schule C. Impact on cortisol and antidepressant efficacy of quetiapine and escitalopram in depression. Psychoneuroendocrinology. 2014 Jan;39:141-151. doi: 10.1016/j.psyneuen.2013.10.008. Epub 2013 Oct 23.
PubMed 24275013
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Quetiapine Prolong and Escitalopram on the Hypothalamic-pituitary-adrenocortical (HPA)-Axis Activity in Depressed Patients
- ClinicalTrials.gov ID
- NCT00953108
- Acronym / sponsor ID
- QUE/09
- Conditions
- Major Depression
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Ludwig-Maximilians - University of MunichUniversity, hospital or other
- Study start
- Sep 2009
- Primary completion
- Feb 2012 (actual)
- Study completion
- Feb 2012 (actual)
- First posted
- 6 Aug 2009 (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.
In former studies of the investigators research group the investigators could also demonstrate acute inhibitory effects of the antidepressant mirtazapine on ACTH and cortisol release in normal controls (Schüle et al. 2002), most likely mediated via antagonism at central 5-HT2- and H1-receptors. In contrast to mirtazapine, serotonin or norepinephrine reuptake inhibiting antidepressants acutely stimulate ACTH and cortisol secretion (Schüle 2007). The investigators also performed a study in depressed patients who were treated either with mirtazapine or with reboxetine using serial dexamethasone/CRH tests (week 0, 1, and 5) as a parameter for HPA axis activity. Mirtazapine, but not the norepinephrine reuptake inhibitor reboxetine was able to significantly reduce HPA axis activity already within one week (Schüle et al. 2006). Mirtazapine is known to have an earlier onset of antidepressant action than do SSRIs such as sertraline (Behnke et al. 2003) or antidepressants with dual mechanism of action such as venlafaxine (Benkert et al. 2006), possibly due to its rapid inhibition of HPA axis activity in unipolar depressed patients.
Since mirtazapine and quetiapine have similar effects on the HPA system in healthy male volunteers (i.e. inhibition of ACTH and cortisol secretion), a rapid attenuation of HPA axis activity is also expected during quetiapine XR treatment in depressed patients.
Therefore, in the present study the investigators goal is to investigate whether quetiapine fumarate XR at a dosage of 300 mg per day has an impact on HPA axis activity in unipolar depressed patients, as measured by serial dexamethasone/CRH tests (week 0, 1, and 5) and salivary cortisol profiles and whether putative effects of quetiapine XR on the HPA system are related to its antidepressant efficacy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| quetiapine | Experimental | Drug: quetiapine |
| escitalopram | Active comparator | Drug: escitalopram |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Inpatients (the admission to hospital occurs independently from study participation)
- Provision of written informed consent
- A diagnosis of major depression by Diagnostic and Statistical Manual of Mental Disorders- Fourth Edition (DSM-IV) (unipolar depression: 296.2, 296.3)
- Female and male patients aged 18 to 65 years
- Female patients of childbearing potential must have a negative serum human chorionic gonadotropin (hCG) pregnancy test at enrolment and e willing to use a reliable method of birth control (i.e. barrier method, oral contraceptive, implant, dermal contraception, long-term injectable contraceptive, intrauterine device, or tubal litigation) during the study.
Key exclusion criteria (31 listed)
- Pregnancy or lactation
- Any DSM-IV Axis I disorder not defined in the inclusion criteria
- Patients who, in the opinion of the investigator, pose an imminent risk of suicide or a danger to self or others
- Known intolerance or lack of response to quetiapine fumarate and/or escitalopram, as judged by the investigator
- Use of any of the following cytochrome P450 3A4 inhibitors in the 14 days preceding enrolment including but not limited to: ketoconazole, itraconazole, fluconazole, erythromycin, clarithromycin, troleandomycin, indinavir, nelfinavir, ritonavir, fluvoxamine and saquinavir
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 |
|---|---|---|
| quetiapine300 mg per day | Drug | quetiapine |
| escitalopramescitalopram 10 mg per day | Drug | escitalopram |
Primary outcome
serial dexamethasone/CRH tests
Time frame: week 0, 1, and 5
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 12 Feb 2013.
- Derived from this study: PubMed 24275013Sarubin N, Nothdurfter C, Schmotz C, Wimmer AM, Trummer J, Lieb M, Uhr M, Baghai TC, Wetter TC, Buhner M, Rupprecht R, Schule C. Impact on cortisol and antidepressant efficacy of quetiapine and escitalopram in depression. Psychoneuroendocrinology. 2014 Jan;39:141-151. doi: 10.1016/j.psyneuen.2013.10.008. Epub 2013 Oct 23.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing quetiapine and escitalopram in people with Major Depression, run by Ludwig-Maximilians - University of Munich 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 8 inclusion and 31 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 12 Feb 2013. 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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
serial dexamethasone/CRH tests (time frame: week 0, 1, and 5). 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 NCT00953108, which also lists 1 linked publication.
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 12 Feb 2013.