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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2012 by Inje University.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
Seung-Hwan Lee, Inje University
ClinicalTrials.gov Identifier:
NCT01357967
First received: May 19, 2011
Last updated: October 31, 2012
Last verified: October 2012
  Purpose

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.


Condition Intervention Phase
Major Depressive Disorder
Drug: SSRI monotherapy
Drug: Seroquel XR adjunctive
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Effect of Quetiapine XR in Depressive Patients Showing Aberrant N100 Amplitude Slope

Resource links provided by NLM:


Further study details as provided by Inje University:

Primary Outcome Measures:
  • Change from baseline in HDRS scale [ Time Frame: 0,1,2,4,6 weeks ] [ Designated as safety issue: Yes ]
    -Hamilton Depression Rating Scale (HDRS) : Baseline, 1, 2, 4, 6 week


Secondary Outcome Measures:
  • Change from baseline in CGI, BDI, and YMRS scales [ Time Frame: 0,1,2,4,6 weeks ] [ Designated as safety issue: Yes ]
    • 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


Estimated Enrollment: 60
Study Start Date: May 2011
Estimated Study Completion Date: April 2013
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Seroquel XR adjunctive

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).

Drug: 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

Other Names:
  • Seroquel XR
  • quetiapine XR
  • quetiapine
Active Comparator: SSRI monotherapy
active comparator
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
Other Name: SSRI

  Hide Detailed Description

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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01357967

Contacts
Contact: Jung In Kim, Mr 82-31-910-7776 p5p52@hanmail.net

Locations
Korea, Republic of
Psychiatry Department, Inje University Ilsan Paik Hospital Recruiting
Goyang, Geyonggi, Korea, Republic of
Principal Investigator: Seung-Hwan Lee, MD, PhD         
Inje University Ilsanpaik Hospital Active, not recruiting
Goyang, Gyeonggi, Korea, Republic of, 411-706
Sponsors and Collaborators
Inje University
Investigators
Principal Investigator: Seung-Hwan Lee, MD, PhD Psychiatry Department Inje University Ilsan Paik Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: Seung-Hwan Lee, Professor, Inje University
ClinicalTrials.gov Identifier: NCT01357967     History of Changes
Other Study ID Numbers: Seroquel ISS D1443C00053
Study First Received: May 19, 2011
Last Updated: October 31, 2012
Health Authority: Korea: Food and Drug Administration
Korea: Institutional Review Board

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Major
Behavioral Symptoms
Mental Disorders
Mood Disorders
Quetiapine
Antipsychotic Agents
Central Nervous System Agents
Central Nervous System Depressants
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Therapeutic Uses
Tranquilizing Agents

ClinicalTrials.gov processed this record on November 25, 2014