Major Depressive DisorderPhase 4NCT01357967
The Effect of Quetiapine XR in Depressive Patients Showing Aberrant N100 Amplitude Slope
A Phase 4 study testing SSRI monotherapy and Seroquel XR adjunctive in people with Major Depressive Disorder, run by Inje University at 2 sites in South Korea.
Trial summary
Recently, there are increasing data about intensity dependent amplitude change (IDAP: N100 amplitude slope) of auditory evoked Event Related Potential (ERP) components for its role on surrogate marker of central serotonergic activity. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- SSRI monotherapy and Seroquel XR adjunctive
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 2 sitesSouth Korea
- Study dates
- May 2011to Apr 2013
- Phase
- Phase 4
- 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
- No healthy volunteers
- Adult
Who may be able to join
- For inclusion in the study patients must fulfill all of the following criteria:
- Major depressive disorder (HRDS > 18)
- N100 amplitude slope outlier (< 0.21 or > 1.59)
- Aged 18 to 55 years
- Provision of written informed consent prior to any study specific procedures
Who cannot join
- Any of the following is regarded as a criterion for exclusion from the study:
- Pregnancy or lactation: : urine HCG (-)
- 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 SSRI antidepressant, as judged by the investigator
- Hearing impairment
Show all 25Show fewer
- Use of any of the following cytochrome P450 3A4 inhibitors in the 14 days preceding enrollment including but not limited to: ketoconazole, itraconazole, fluconazole, erythromycin, clarithromycin, troleandomycin, indinavir, nelfinavir, ritonavir, fluvoxamine and saquinavir
- Use of any of the following cytochrome P450 3A4 inducers in the 14 days preceding enrollment including but not limited to: phenytoin, carbamazepine, barbiturates, rifampin, St. John's Wort, and glucocorticoids
- Administration of a depot antipsychotic injection within one dosing interval (for the depot) before randomisation/baseline
- Substance or alcohol dependence at enrollment (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 enrollment
- 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 or clinically relevant abnormal laboratory values) as judged by the investigator
- Involvement in the planning and conduct of the study
- Previous enrollment or randomisation of treatment in the present study.
- Participation in another drug trial within 4 weeks prior enrollment 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 enrollment 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 1,000,000,000 per liter
Trial locations and contacts
2 sites in 1 country.
South Korea2 sites, 1 recruiting
- Recruiting
Psychiatry Department, Inje University Ilsan Paik Hospital
Goyang, Geyonggi
Seung-Hwan Lee, MD, PhD
- Active, not recruiting
Inje University Ilsanpaik Hospital
Goyang-si, Gyeonggi-do, 411-706
About this study
Recently, there are increasing data about intensity dependent amplitude change (IDAP: N100 amplitude slope) of auditory evoked Event Related Potential (ERP) components for its role on surrogate marker of central serotonergic activity. A high N100 amplitude slope reflects low serotonergic neurotransmission and vice versa. There are a couple of studies reporting associations of N1 amplitude slope with response to Citalopram (positive correlation) and Reboxetine (negative correlation) treatment in major depressive disorder patients (2,3). The investigator also published a case series about SSRI super-sensitivity and SSRI induced mania in patients with aberrantly high N100 slope (4). And serotonin transporter gene polymorphism was studied for its role about pathophysiology of bipolar disorder (5, 6, 7). Serotonin promoter gene was known to have significant relationship with N100 amplitude slope (8). Furthermore previous study showed that N100 amplitude slope was well correlated with hypomanic and hyperthymic personality (9).
Conclusively from above results, the investigator hypothesized that if depressive patients show aberrant high or low N100 amplitude slope (N100 response outliers), they will not response well to SSRI medication. They will response better to quetiapine XR adjunctive therapy. In this study, the investigator will confirm it by comparing treatment effect between SSRI monotherapy and quetiapine XR adjunctive in aberrant N100 responder.
Read more
Hypothesis First visit depressive patients might have monopolar or bipolar depression. If depressive patients show aberrantly high or low N100 amplitude slope, they will not response to SSRI medication.
Patients who have aberrantly high or low N100 amplitude slope will response better to quetiapine XR adjunctive therapy.
Read the detailed description
1.2 Rationale for this study The development of better strategy for treatment of major depressive disorder and other mood disorder is a very important issue for patients, mental health provider and government. So far, treatments of depressive illness have been based on mainly trial and error method and physician's personal experiences.
So the development of new strategy for predicting better treatment response group of quetiapine XR would be great contributions for basic brain science and mental health fields.
- STUDY OBJECTIVES
2.1 Primary objective
Primary target of this study is to prove the following hypothesis :
Patients who have aberrantly high or low N100 amplitude slope will response better to quetiapine XR adjunctive therapy.
2.2 Secondary objectives
Patients who have aberrantly high or low N100 amplitude slope will show higher dropout rate for SSRI monotherapy compared to quetiapine XR adjunctive.
- STUDY PLAN AND PROCEDURES
3.1 Overall study design and study plan
This study will be conducted by open, randomized, two armed, and observational phase IV study. The investigator will compare treatment response between Quetiapine XR and SSRIs to major depressive disorder patients showing aberrant response of N100 amplitude slope. The investigator will use SSRIs drugs (paxil CR, es-citalopram, fluoxetine, sertraline) as comparator drug. The investigator will recruit drug naive patients but if there were previous antidepressant medication, washout periods will be required for one week. This study will be conducted as single centre study, and patients will be enrolled based on the DSM-IV major depressive disorder criteria, and also aberrant response of N100 amplitude (N100 slope < 0.21, or > 1.59, this criteria can be revised base on our newly published data). In and out-patients status of patients will recruited together. The treatment duration will be six weeks from beginning of pharmacological treatment.
Procedure for measuring the LDAEP (N100 amplitude slope)
Recording took place in an electrically shielded and sound attenuated room adjacent to the recording apparatus (Synamps, Neuroscan ®). Subjects were seated with open eyes in a slightly reclined chair with a head rest. Evoked responses were recorded with 32 electrodes referred to Cz. Pure sinus tones (1000 Hz, 80 ms duration with 10 ms rise and 10 ms fall time, ISI randomized between 500 and 900 ms) of 5 intensities (55, 65, 75, 85, 95 dB sound pressure level) were presented binaurally in a pseudo-randomised form by audiometry headphones. Data were collected with a sampling rate of 1000 Hz and an analogous bandpass filter (1-30 Hz). Analysis was performed with the Scan® software package version 4.3. One hundred ms prestimulus and 300 ms poststimulus periods were evaluated for about 100 sweeps of every intensity (all together 500 sweeps). For artifact suppression, all trials were automatically excluded from averaging, if the voltage exceeded ± 70uV in any one of the 32 channels at any time point of the averaging period. For each subject, the remaining sweeps were averaged separately for the five stimulus intensities. At least 30 artefact-free sweeps/intensity had to be averaged. N1 peaks (80-140 ms) and P2 peaks (100-250 ms) were determined semi-automatically at the Cz electrode (referred to linked-mastoids). The IDAP was calculated as linear regression slope with stimulus intensity as independent and N1/P2 amplitude as dependent variable.
- Conditions
- Major Depressive Disorder
- Being tested
- SSRI monotherapy, Seroquel XR adjunctive
- 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.
SSRI monotherapyDrug
Also called SSRI
SSRI (paxil CR, es-citalopram, fluoxetine, sertraline) start with (paxil CR 12.5mg, es-citalopram 10mg, fluoxetine 20mg, sertraline 50mg) for 1 week up to maximal dosage, flexible dosage, usually in the morning
Seroquel XR adjunctiveDrug
Also called Seroquel XR, quetiapine XR, quetiapine
Quetiapine group:
seroquel XR 50mg Day 1 --> 50mg Day 2 --> 150mg Day 3 --> 150mg Day 4 --> adjustment usually at hs but can be daytime
| Study group | Role | What they receive |
|---|---|---|
| Seroquel XR adjunctive | Experimental | The quetiapine XR adjunct group will be titrated up to 300mg. Initial dosing will begin at 50mg on Day 1 and 2, increased to 150mg on Day 3 and 4. Further adjustments will be able to be made upwards or downwards within the recommended dose range of 50mg to 300mg depending upon the clinical response and tolerance of the patient. Seroquel XR will be administered daily in the evening.
The dosage of SSRIs will be maintained as low (es-citalopram 5mg, paxil CR 6.25mg, fluoxetine 10mg, and sertraline 25mg). Receives: Drug: Seroquel XR adjunctive |
| SSRI monotherapy | Active comparator | active comparator Receives: Drug: SSRI monotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in HDRS scale
-Hamilton Depression Rating Scale (HDRS) : Baseline, 1, 2, 4, 6 week
Measured: 0,1,2,4,6 weeks
Secondary outcomes (1)
Change from baseline in CGI, BDI, and YMRS scales
- Clincal Global Impression (CGI) : Baseline, 1, 2, 4, 6 week
- Beck Depression Inventory (BDI) : Baseline, 1, 2, 4, 6 week
- Young Mania rating Scale (YMRS) : Baseline, 1, 2, 4, 6 week
Measured: 0,1,2,4,6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2011 (estimated)
- Study startMay 2011
- Primary completionDec 2012 (estimated)
- Study completionApr 2013 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Inje University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Seung-Hwan Lee, Inje University
- Investigators
- Seung-Hwan Lee, MD, PhD, Principal investigator, Psychiatry Department Inje University Ilsan Paik Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01357967
- Sponsor's protocol ID
- Seroquel ISS D1443C00053
- Status last verified
- Oct 2012
- First submitted
- 19 May 2011
- Last updated
- 1 Nov 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Quetiapine XR in Depressive Patients Showing Aberrant N100 Amplitude Slope
- ClinicalTrials.gov ID
- NCT01357967
- Acronym / sponsor ID
- Seroquel ISS D1443C00053
- Conditions
- Major Depressive Disorder
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Inje UniversityUniversity, hospital or other
- Study start
- May 2011
- Primary completion
- Dec 2012 (estimated)
- Study completion
- Apr 2013 (estimated)
- First posted
- 23 May 2011 (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.
Recently, there are increasing data about intensity dependent amplitude change (IDAP: N100 amplitude slope) of auditory evoked Event Related Potential (ERP) components for its role on surrogate marker of central serotonergic activity. A high N100 amplitude slope reflects low serotonergic neurotransmission and vice versa. There are a couple of studies reporting associations of N1 amplitude slope with response to Citalopram (positive correlation) and Reboxetine (negative correlation) treatment in major depressive disorder patients (2,3). The investigator also published a case series about SSRI super-sensitivity and SSRI induced mania in patients with aberrantly high N100 slope (4). And serotonin transporter gene polymorphism was studied for its role about pathophysiology of bipolar disorder (5, 6, 7). Serotonin promoter gene was known to have significant relationship with N100 amplitude slope (8). Furthermore previous study showed that N100 amplitude slope was well correlated with hypomanic and hyperthymic personality (9).
Conclusively from above results, the investigator hypothesized that if depressive patients show aberrant high or low N100 amplitude slope (N100 response outliers), they will not response well to SSRI medication. They will response better to quetiapine XR adjunctive therapy. In this study, the investigator will confirm it by comparing treatment effect between SSRI monotherapy and quetiapine XR adjunctive in aberrant N100 responder.
Hypothesis First visit depressive patients might have monopolar or bipolar depression. If depressive patients show aberrantly high or low N100 amplitude slope, they will not response to SSRI medication.
Patients who have aberrantly high or low N100 amplitude slope will response better to quetiapine XR adjunctive therapy.
Detailed description
1.2 Rationale for this study The development of better strategy for treatment of major depressive disorder and other mood disorder is a very important issue for patients, mental health provider and government. So far, treatments of depressive illness have been based on mainly trial and error method and physician's personal experiences.
So the development of new strategy for predicting better treatment response group of quetiapine XR would be great contributions for basic brain science and mental health fields.
- STUDY OBJECTIVES
2.1 Primary objective
Primary target of this study is to prove the following hypothesis :
Patients who have aberrantly high or low N100 amplitude slope will response better to quetiapine XR adjunctive therapy.
2.2 Secondary objectives
Patients who have aberrantly high or low N100 amplitude slope will show higher dropout rate for SSRI monotherapy compared to quetiapine XR adjunctive.
- STUDY PLAN AND PROCEDURES
3.1 Overall study design and study plan
This study will be conducted by open, randomized, two armed, and observational phase IV study. The investigator will compare treatment response between Quetiapine XR and SSRIs to major depressive disorder patients showing aberrant response of N100 amplitude slope. The investigator will use SSRIs drugs (paxil CR, es-citalopram, fluoxetine, sertraline) as comparator drug. The investigator will recruit drug naive patients but if there were previous antidepressant medication, washout periods will be required for one week. This study will be conducted as single centre study, and patients will be enrolled based on the DSM-IV major depressive disorder criteria, and also aberrant response of N100 amplitude (N100 slope < 0.21, or > 1.59, this criteria can be revised base on our newly published data). In and out-patients status of patients will recruited together. The treatment duration will be six weeks from beginning of pharmacological treatment.
Procedure for measuring the LDAEP (N100 amplitude slope)
Recording took place in an electrically shielded and sound attenuated room adjacent to the recording apparatus (Synamps, Neuroscan ®). Subjects were seated with open eyes in a slightly reclined chair with a head rest. Evoked responses were recorded with 32 electrodes referred to Cz. Pure sinus tones (1000 Hz, 80 ms duration with 10 ms rise and 10 ms fall time, ISI randomized between 500 and 900 ms) of 5 intensities (55, 65, 75, 85, 95 dB sound pressure level) were presented binaurally in a pseudo-randomised form by audiometry headphones. Data were collected with a sampling rate of 1000 Hz and an analogous bandpass filter (1-30 Hz). Analysis was performed with the Scan® software package version 4.3. One hundred ms prestimulus and 300 ms poststimulus periods were evaluated for about 100 sweeps of every intensity (all together 500 sweeps). For artifact suppression, all trials were automatically excluded from averaging, if the voltage exceeded ± 70uV in any one of the 32 channels at any time point of the averaging period. For each subject, the remaining sweeps were averaged separately for the five stimulus intensities. At least 30 artefact-free sweeps/intensity had to be averaged. N1 peaks (80-140 ms) and P2 peaks (100-250 ms) were determined semi-automatically at the Cz electrode (referred to linked-mastoids). The IDAP was calculated as linear regression slope with stimulus intensity as independent and N1/P2 amplitude as dependent variable.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Seroquel XR adjunctive | Experimental | Drug: Seroquel XR adjunctiveThe quetiapine XR adjunct group will be titrated up to 300mg. Initial dosing will begin at 50mg on Day 1 and 2, increased to 150mg on Day 3 and 4. Further adjustments will be able to be made upwards or downwards within the recommended dose range of 50mg to 300mg depending upon the clinical response and tolerance of the patient. Seroquel XR will be administered daily in the evening. The dosage of SSRIs will be maintained as low (es-citalopram 5mg, paxil CR 6.25mg, fluoxetine 10mg, and sertraline 25mg). |
| SSRI monotherapy | Active comparator | Drug: SSRI monotherapyactive comparator |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Major depressive disorder (HRDS > 18)
- N100 amplitude slope outlier (< 0.21 or > 1.59)
- Aged 18 to 55 years
- Provision of written informed consent prior to any study specific procedures
Key exclusion criteria (25 listed)
- Pregnancy or lactation: : urine HCG (-)
- 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 SSRI antidepressant, as judged by the investigator
- Hearing impairment
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 |
|---|---|---|
| SSRI monotherapyAlso: SSRISSRI (paxil CR, es-citalopram, fluoxetine, sertraline) start with (paxil CR 12.5mg, es-citalopram 10mg, fluoxetine 20mg, sertraline 50mg) for 1 week up to maximal dosage, flexible dosage, usually in the morning | Drug | SSRI monotherapy |
| Seroquel XR adjunctiveAlso: Seroquel XR, quetiapine XR, quetiapineQuetiapine group: seroquel XR 50mg Day 1 --> 50mg Day 2 --> 150mg Day 3 --> 150mg Day 4 --> adjustment usually at hs but can be daytime | Drug | Seroquel XR adjunctive |
Primary outcome
Change from baseline in HDRS scale
Time frame: 0,1,2,4,6 weeks
-Hamilton Depression Rating Scale (HDRS) : Baseline, 1, 2, 4, 6 week
1 secondary outcome
Change from baseline in CGI, BDI, and YMRS scales
Time frame: 0,1,2,4,6 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2012.
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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.
Seung-Hwan Lee, MD, PhD principal investigator
Psychiatry Department Inje University Ilsan Paik Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing SSRI monotherapy and Seroquel XR adjunctive in people with Major Depressive Disorder, run by Inje University at 2 sites in South Korea.
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 25 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: status not confirmed, as of the sponsor's last update on 1 Nov 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in South Korea. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jung In Kim, Mr (82-31-910-7776, p5p52@hanmail.net), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline in HDRS scale (time frame: 0,1,2,4,6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 1 Nov 2012.