The Effect of Quetiapine XR in Depressive Patients Showing Aberrant N100 Amplitude Slope

Major Depressive Disorder Clinical Trial

Official title:

The Effect of Quetiapine XR in Depressive Patients Showing Aberrant N100 Amplitude Slope

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01357967
• Other study ID #: Seroquel ISS D1443C00053
• Status: Recruiting
• Phase: Phase 4
• First received: May 19, 2011
• Last updated: October 31, 2012
• Start date: May 2011
• Est. completion date: April 2013

Study information

• Verified date: October 2012
• Source: Inje University
• Contact: Jung In Kim, Mr
• Phone: 82-31-910-7776
• Email: p5p52[@]hanmail.net
• Is FDA regulated: No
• Health authority: Korea: Food and Drug AdministrationKorea: Institutional Review Board
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: April 2013
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

For inclusion in the study patients must fulfill all of the following criteria:

1. Major depressive disorder (HRDS > 18)

2. N100 amplitude slope outlier (< 0.21 or > 1.59)

3. Aged 18 to 55 years

4. Provision of written informed consent prior to any study specific procedures

Exclusion Criteria:

Any of the following is regarded as a criterion for exclusion from the study:

1. Pregnancy or lactation: : urine HCG (-)

2. Any DSM-IV Axis I disorder not defined in the inclusion criteria

3. Patients who, in the opinion of the investigator, pose an imminent risk of suicide or a danger to self or others

4. Known intolerance or lack of response to quetiapine fumarate and SSRI antidepressant, as judged by the investigator

5. Hearing impairment

6. 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

7. 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

8. Administration of a depot antipsychotic injection within one dosing interval (for the depot) before randomisation/baseline

9. Substance or alcohol dependence at enrollment (except dependence in full remission, and except for caffeine or nicotine dependence), as defined by DSM-IV criteria

10. Opiates, amphetamine, barbiturate, cocaine, cannabis, or hallucinogen abuse by DSM-IV criteria within 4 weeks prior to enrollment

11. Medical conditions that would affect absorption, distribution, metabolism, or excretion of study treatment

12. 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

13. Involvement in the planning and conduct of the study

14. Previous enrollment or randomisation of treatment in the present study.

15. Participation in another drug trial within 4 weeks prior enrollment into this study or longer in accordance with local requirements

16. 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.

17. An absolute neutrophil count (ANC) of <= 1.5 x 1,000,000,000 per liter

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

Drug:
• SSRI monotherapy
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 adjunctive
Quetiapine group: seroquel XR 50mg Day 1 --> 50mg Day 2 --> 150mg Day 3 --> 150mg Day 4 --> adjustment usually at hs but can be daytime

Locations

Country	Name	City	State
Korea, Republic of	Inje University Ilsanpaik Hospital	Goyang	Gyeonggi
Korea, Republic of	Psychiatry Department, Inje University Ilsan Paik Hospital	Goyang	Geyonggi

Sponsors (1)

Lead Sponsor	Collaborator
Inje University

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in HDRS scale	-Hamilton Depression Rating Scale (HDRS) : Baseline, 1, 2, 4, 6 week	0,1,2,4,6 weeks	Yes
Secondary	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	0,1,2,4,6 weeks	Yes

External Links

•   Homepage of principal investigator