Ignite Creation Date:
2025-12-25 @ 12:40 AM
Ignite Modification Date:
2025-12-27 @ 4:51 AM
Study NCT ID:
NCT01357967
Status:
UNKNOWN
Last Update Posted:
2012-11-01
First Post:
2011-05-19
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
The Effect of Quetiapine XR in Depressive Patients Showing Aberrant N100 Amplitude Slope
Sponsor:
Inje University
Organization:
Study Overview
Official Title:
The Effect of Quetiapine XR in Depressive Patients Showing Aberrant N100 Amplitude Slope
Status:
UNKNOWN
Status Verified Date:
2012-10
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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. 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.
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.
2\. 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.
3\. 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.
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.
2\. 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.
3\. 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 Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: