Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12610000937011
Ethics application status
Not yet submitted
Date submitted
21/10/2010
Date registered
4/11/2010
Date last updated
4/03/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
Prevention of Lowered Mood in Major Depressive Disorder with Quetiapine extended release after remission has been induced by electroconvulsive therapy (ECT)
Scientific title
PREQUEL study- Prevention after ECT with Quetiapine extended release of Lowered Mood (in remitted Major Depressive Disorder following ECT)
Secondary ID [1] 252902 0
Not applicable
Universal Trial Number (UTN)
U1111-1117-5227
Trial acronym
PREQUEL
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Major Depressive Disorder (MDD) 258439 0
Condition category
Condition code
Mental Health 258604 258604 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a multicentre (St Vincent's Melbourne, The Melbourne Clinic and The Albert Road Clinic) clinical study of patients with a DSM-IV TR MDD, who have failed to respond to an adequate trial of at least one antidepressant (SSRI or SNRI) or when ECT is the preferred treatment.
Randomization will be into two parallel groups of 20 participants (outpatients and/or inpatients) each.
One group will be treated with Quetiapine XR (flexible dose of 50 to 300 mg daily orally, with dose changes determined by CGI-I scores and tolerability) in combination with TAU (SSRI/SNRI not previously prescribed) and the other group with TAU. TAU is determined by the treating clinician’s selection of monotherapy of a single antidepressant (SSRI/SNRI) at therapeutic dosage and not previously associated with failed response/poor tolerability. The dose range of Quetiapine XR will be flexibly adjusted from 50mg to 300 mg orally. Changes in study medication dose are made according to clinical response (continuation of the current dose if HAMD less than or equal to 7 and CGI-I less than or equal to 3 and increase in dose by 100 mg if HAMD > 7 and < 15 and CGI-I > 3) and tolerability (including as measured by SAS (Simpson and Angus, 1970) and LUNSERS (Day et al, 1995).The duration of treatment will be up to 6 months.
Intervention code [1] 257435 0
Treatment: Drugs
Intervention code [2] 257532 0
Prevention
Comparator / control treatment
Treatment as usual-TAU (SSRI/SNRI not previously prescribed)
Control group
Active

Outcomes
Primary outcome [1] 259452 0
The primary outcome measure is the magnitude of depressive symptoms is measured by the Hamilton Depresion Rating Scale (HAMD) score.
The primary objective will also be assessed by the prevention of depressive relapse, measured by the HAMD. Depressive relapse is defined as HAMD greater than or equal to 15.
Timepoint [1] 259452 0
Participants will be reviewed weekly for first month and monthly for 6 months in total. The total assessment time is 6 months.
Secondary outcome [1] 266010 0
Clinical Global Impression (CGI-I)-Global Improvement Scale.
Timepoint [1] 266010 0
Participants will be reviewed weekly for first month and monthly for 6 months in total. The total assessment time is 6 months.

Eligibility
Key inclusion criteria
*Provision of written informed consent prior to any study specific procedures
*A diagnosis of Major Depressive Disorder by Diagnostic and Statistical Manual of Mental Disorders- Fourth Edition, Text-Revision (DSM-IV TR)
*Males and females aged 18 to 65 years.
*HAMD less than or equal to 7 following a course of ECT which produces remission of depression (HAMD = 7) that is sustained over the last two ECT treatments in the course of ECT, after failure to respond to an adequate trial of at least one antidepressant medication (SSRI or SNRI) or when ECT is the preferred treatment.
* Completion of acute course of ECT within 3 weeks of baseline.
*Female patients of childbearing potential must be using a reliable method of contraception and have a negative urine human chorionic gonadotropin (HCG) test at enrolment
*Able to understand and comply with the requirements of the study.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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 SSRI/SNRI , 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
*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
*Administration of a depot antipsychotic injection within one dosing interval (for the depot) before randomisation/baseline
*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 or clinically relevant abnormal laboratory values) 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:
a)Unstable DM defined as enrolment glycosylated hemoglobin (HbA1c) >8.5%.
b)Admitted to hospital for treatment of DM or DM related illness in past 12 weeks.
c)Not under physician care for DM
d)Physician responsible for patient’s DM care has not indicated that patient’s DM is controlled.
e)Physician responsible for patient’s DM care has not approved patient’s participation in the study
f)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.
g)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 less than or equal to 1.5 x 10 to the 9 per litre

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Patient eligibility will be established before treatment randomisation. Patients will be randomised strictly sequentially, as patients are eligible for enrolment/randomisation. If a patient discontinues from the study, the patient number will not be reused, and the patient will not be allowed to re-enter the study.
This is an open-label study. The treatment allocation is based on random assignment of individual participants based on a computer-generated sequence. The randomization sequence/code will be concealed from all personnel, but the treatment thereafter will not.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer-generated.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Date of first participant enrolment
Anticipated
1/03/2011
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
40
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 257873 0
Commercial sector/Industry
Name [1] 257873 0
AstraZeneca
Country [1] 257873 0
Australia
Primary sponsor type
Hospital
Name
St Vincent's Hospital
Address
46 Nicholson St
Fitzroy, 3065, Melbourne, Vic.
Country
Australia
Secondary sponsor category [1] 257073 0
None
Name [1] 257073 0
Address [1] 257073 0
Country [1] 257073 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 259902 0
St Vincent's Hospital, Melbourne
Ethics committee address [1] 259902 0
PO Box 2900, Fitzroy VIC 3065
Ethics committee country [1] 259902 0
Australia
Date submitted for ethics approval [1] 259902 0
28/10/2010
Approval date [1] 259902 0
Ethics approval number [1] 259902 0

Summary
Brief summary
There is emerging that the medication, Quetiapine (trade name: Seroquel) is clinically useful in treating clinically significant depression (major depressive disorder) and in the augmentation of antidepressant medication in this condition and depression that occurs in bipolar disorder (manic-depression). Quetiapine is currently approved for the treatment of schizophrenia and bipolar disorder.

This study will look at whether the addition of the medication Quetiapine XR (trade name: Seroquel XR) to standard antidepressant medication is better than antidepressant medication alone in keeping symptoms of depression to a minimum after a clinically beneficial course of electroconvulsive therapy (ECT) within the previous 3 weeks for clinical depression (major depressive disorder). Participation in the study will occur after remission (disappearance) of clinically significant depression has occurred after treatment with ECT, when there has been failure to respond to an adequate trial of at least one antidepressant medication, or when ECT is the preferred treatment.

People will be invited to participate in the study if they: are aged 18-65 years ;have
been diagnosed as experiencing major depressive disorder; have had a course of ECT
completed within the previous 3 weeks, which has led to remission of depression
sustained over the last 2 ECT treatments of the ECT course, after failure to respond to
an adequate trial of at least one antidepressant medication, or when ECT is the
preferred treatment. People will not be able to participate in the study if they are: at
immediate risk to themselves or others; dependent on alcohol or other substances,
apart from caffeine or nicotine; or have diabetes mellitus that is not stable or well
controlled. Women who are pregnant, or may become pregnant, or are lactating
during the course of the study, will also not be able to participate in the study.

There will be 2 groups of 20 participants, each, in the study. One group will be treated with the medication Quetiapine XR in combination with an antidepressant medication. Another group will be treated with an antidepressant medication alone. The antidepressant medications, either a selective serotonin reuptake inhibitors (SSRI) or serotonin and noradrenaline reuptake inhibitor (SNRI) that has not been previously prescribed, or previously not helpful in preventing relapse of clinically significant depression, will be prescribed by treating doctors. The addition of Quetiapine XR to the antidepressant medication will be randomly determined, so that the study doctors or treating doctors will have no prior knowledge nor influence on whether this medication is added to prescribed antidepressant medication. The dose of Quetiapine XR will range from 50 milligrams to a maximum of 300 milligrams per day, with doses adjusted according to clinical response to, and tolerability of this medication. Psychiatric medications other than the prescribed antidepressant medication or Quetiapine XR, will not be prescribed or permitted during the course of the study.

The duration of the study is 6 months, with weekly study visits for the first month and monthly, thereafter for the remaining 5 months. Participants will be asked questions about the presence of depressive symptoms and how they are tolerating their medication, as well as a physical examination as part of each study visit. Participants will have blood tests (clinical chemistry, haematology) prior to commencing the study, and at 1,2,3 and 6 months. Participants will also have a fasting (not having eaten, or drunk anything other than water since midnight) prior to commencing the study, and at 3 and 6 months. Participants will also have a urine drug test and electrocardiogram (ECG) prior to commencement. Participants will be free to withdraw their consent at any stage without affecting or prejudicing their clinical care in any way. In the event of depressive relapse (recurrence of clinically significant depression), participants will be discontinued from study, with alternative treatment arrangements made in consultation with their primary treating medical practitioner.
Trial website
Not applicable
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 31797 0
A/Prof A/Prof Peter Bosanac
Address 31797 0
This has not changed
Country 31797 0
Australia
Phone 31797 0
+61392884329
Fax 31797 0
Email 31797 0
[email protected]
Contact person for public queries
Name 15044 0
Dr Peter Bosanac
Address 15044 0
46 Nicholson St, Fitzroy 3065, Melbourne, Vic.
Country 15044 0
Australia
Phone 15044 0
+61392884329
Fax 15044 0
Email 15044 0
[email protected]
Contact person for scientific queries
Name 5972 0
Dr Peter Bosanac
Address 5972 0
46 Nicholson St, Fitzroy 3065, Melbourne, Vic.
Country 5972 0
Australia
Phone 5972 0
+61392884329
Fax 5972 0
Email 5972 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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No documents have been uploaded by study researchers.

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