Depression With Prominent AgitationPhase 3NCT01363310
The Quietude Study: Quetiapine Use for Agitated Depression
A Phase 3 study testing Quetiapine XR and Escitalopram in people with Depression With Prominent Agitation, run by Physicians Research And Education Network at 11 sites in Canada.
Trial summary
Most individuals with major depressive disorder manifest clinically significant agitation. Concurrent agitation in a depressed individual is associated with an intensification of mood symptoms, decreased probability of recovery, increased recurrence risk, suicidality, and increased medical-service utilization. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Depression With Prominent Agitation
- What is being tested?
- Quetiapine XR and Escitalopram
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 250 participants
- Where
- 11 sitesCanada
- Study dates
- Oct 2010to Feb 2013
- Phase
- Phase 3
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female
- Age 18 to 65
- Outpatient at enrolment
- A diagnosis of major depressive disorder
- Baseline HAMD-17 score > 20 and HAMD Item1 score > 2 both at enrolment and baseline
- Significant agitation
Show all 10Show fewer
- CGI-S score > 4 at screening and baseline
- Negative serum pregnancy test at enrolment and use of a reliable method of birth control during the study
- Able to understand and comply with the requirements of the study
- Able and willing to give meaningful informed written consent
Who cannot join
- Another Axis I diagnosis of primary focus within 6 months of enrolment
- Axis II disorder causing impact on current diagnosis
- Current depressive episode <4 weeks, or >12 months
- Substance or alcohol abuse or dependency as defined by DSM IV within 6 months of enrolment
- Any pervasive developmental disorder or dementing disorder
- Treatment with other antipsychotics, mood stabilizer or other psychoactive drugs less than 7 days prior to randomization
Show all 35Show fewer
- Treatment with fluoxetine less than 28 days prior to baseline
- Treatment with MAO inhibitors, anxiolytic drugs in excess of 2 mg lorazepam equivalents/day.
- Insufficient response to more than two antidepressants during the index episode prior to study involvement
- Known lack of antidepressant response to quetiapine at a dose of at least 50 mg/day x 4 weeks
- Known lack of antidepressant response to escitalopram at a dose of at least 10 mg/day
- Known intolerance or hypersensitivity to quetiapine or escitalopram
- Treatment with Electroconvulsive therapy within 90 days prior to baseline
- Use of Potent P450 3A4 inhibitors or inducers within 14 days of baseline
- AST \& ALT ≥ 3X ULN
- TSH ≥ 10% ULN
- Unstable medical condition
- Medical condition the would affect absorption, distribution, metabolism or excretion of study treatment
- Significant ECG abnormalities
- Pregnancy or lactation
- Patients with increased suicidal risks, HAM-D item 3 ≥3 or have made a suicide attempt within the past 6 months.
- Patients who, in the investigators opinion, will require psychotherapy (other than supportive psychotherapy) during the study period, unless psychotherapy has been ongoing for a minimum of 3 months prior to randomisation
- A patient with Diabetes Mellitus (DM) fulfilling one of the following criteria:
- Unstable DM defined as enrolment glycosylated haemoglobin (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
- Clinically significant deviation from the reference range in clinical laboratory test results
- An absolute neutrophil count (ANC) of 1.5 x 109 per liter
- Those who are involved in the planning and/or conduct of the study cannot be enrolled as subjects
- Previous enrolment or randomization in the present study
- Participation in another medication trial within 4 weeks prior to enrolment into the study herein
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
Canada11 sites
Aggarwal and Associates Ltd
Brampton, Ontario, L6T 0G1
Aptekar Medicine Professional Corporation
Brampton, Ontario, L6W 2A4
Chatham-Kent Health Alliance
Chatham, Ontario, N7L 1B7
Fort Erie Group Family Practice
Fort Erie, Ontario, L2A 1Z3
Brady Clinic
Greater Sudbury, Ontario, P3E 1H5
Georgina Family Medical Centre
Keswick, Ontario, L4P 2C7
Richmond Oxford Walk-In Clinic
London, Ontario, N6A 5G6
Gerald Rockman Medicine Professional Corporation
Scarborough Village, Ontario, M1N 1W8
Bloor-Park Medical Centre
Toronto, Ontario, M6G 1L4
Primary Care Lung
Toronto, Ontario, M6H 3M2
Manna Research
Toronto, Ontario, M9W 4L6
About this study
Official title: A Multi-Centre, Double-Blind, Randomised, Parallel Group, Escitalopram Controlled Phase III-B Study of the Efficacy and Safety of Quetiapine Fumarate Extended Release (Seroquel XR TM) as Monotherapy in the Treatment of Adult Patients With Agitated Major Depressive Disorder
Most individuals with major depressive disorder manifest clinically significant agitation. Concurrent agitation in a depressed individual is associated with an intensification of mood symptoms, decreased probability of recovery, increased recurrence risk, suicidality, and increased medical-service utilization. The occurrence of anxiety/agitation phenomenology in the depressed patient often invites the need for augmentation strategies (e.g. atypical antipsychotics, benzodiazepines, etc.) and complicated polypharmacy regimens. Moreover, individuals with major depressive disorder often report worsening of symptom severity, irritability, hostility, dysphoria, and significant subjective distress (This response pattern is similar to individuals with bipolar disorder).
Results from large research studies provide evidence indicating that quetiapine is capable of offering clinically significant multidimensional symptom relief in bipolar depression. Moreover, results from several trials in major depressive disorder and generalized anxiety disorder have established the efficacy of quetiapine therapy for unipolar depression and anxiety syndromes. So far, no atypical antipsychotic agent has been evaluated specifically for the treatment of agitated depression.
In this study, it is hypothesized that persons with major depressive disorder and prominent agitation (i.e. agitated depression) will exhibit a more favourable response and tolerability profile to quetiapine XR when compared to escitalopram.
- Conditions
- Depression With Prominent Agitation
- Being tested
- Quetiapine XR, Escitalopram
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Quetiapine XRDrug
Also called Seroquel XR
Dosage form: tablets Day 1-2: 50 mg Day 3-7: 150 mg Day 8-57: either 150 or 300 mg/day (flexible)
EscitalopramDrug
Dosage form: capsules Day 1-7: 10 mg Day 8-57: 10 or 20 mg/day (flexible)
| Study group | Role | What they receive |
|---|---|---|
| Quetiapine XR | Active comparator | Not described Receives: Drug: Quetiapine XR |
| Escitalopram | Active comparator | Not described Receives: Drug: Escitalopram |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline to endpoint in the Hamilton Depression Rating Scale 17-Item (HAMD-17) total score
A tool to assess the range of symptoms of depression
Measured: Day 1, Day 57
Secondary outcomes (14)
Change in anxiety factor score on the Hamilton Depression Rating Scale 17-item (HAMD-17) from baseline to endpoint
A tool to assess the range of symptoms of depression
Measured: Day 1, Day 57
Change from baseline to endpoint in Hamilton Anxiety Rating Scale (HAMA) total score
A tool to measure severity of symptoms of anxiety
Measured: Day 1, Day 57
Change in Clinical Global Impression score from baseline to endpoint
A tool to assess illness severity, improvement and response to treatment
Measured: Screening Visit, Day 1, Day 8, Day 15, Day 29, Day 43, Day 57
Change from baseline to endpoint in Sheehan Disability Scale (SDS) sub-scales and total score
A tool to assess functional impairment
Measured: Day 1, Day 57
Change in Hamilton Depression Rating Scale 17-item (HAMD-17) sleep disturbance factor score on the from baseline to endpoint
A tool to assess the range of symptoms of depression
Measured: Day 1, Day 57
Change in Hamilton Anxiety Rating Scale (HAMA) somatic and psychic anxiety factor scores from baseline to endpoint
A tool to measure severity of symptoms of anxiety
Measured: Day 1, Day 57
Change from baseline in the Sex Functioning Questionnaire (Sex FX)
A tool to assess sexual functioning
Measured: Day 1, Day 57
Change in blood pressure and heart rate from baseline to end of treatment
Measured: Day 1, Day 57
Change in weight, BMI, waist circumference from baseline to end of treatment
Measured: Day 1, Day 57
Change in findings from physical examination from baseline to end of treatment
Measured: Screening, Day 57
Tabulation of spontaneous adverse events
Measured: Day 1, Day 57
Tabulation of clinical haematology and chemistry results
Measured: Screening, Day 57
Incidence of premature study withdrawal due to inadequate control of depressive symptoms
Proportion of patients with HAM-D Item 3 score > 2 at any time after randomization or adverse events of suicidality/suicidal ideation/suicide attempts/suicide completion
Measured: Day 1, Day 57
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jun 2011 (estimated)
- Study startOct 2010
- Primary completionJan 2013
- Study completionFeb 2013
Why it stopped: Termination of sponsorship
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Depression With Prominent AgitationStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 250 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Physicians Research And Education Network
- Sponsor type
- University, hospital or other
- Investigators
- Roger McIntyre, MD, FRCPC, Study director, Physicians Research And Education Network
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01363310
- Sponsor's protocol ID
- D1443C00037
- Status last verified
- Jan 2014
- First submitted
- 20 May 2011
- Last updated
- 8 Jan 2014
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-Centre, Double-Blind, Randomised, Parallel Group, Escitalopram Controlled Phase III-B Study of the Efficacy and Safety of Quetiapine Fumarate Extended Release (Seroquel XR TM) as Monotherapy in the Treatment of Adult Patients With Agitated Major Depressive Disorder
- ClinicalTrials.gov ID
- NCT01363310
- Acronym / sponsor ID
- D1443C00037
- Conditions
- Depression With Prominent Agitation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Termination of sponsorship
- Enrolment
- 250 participants (estimated)
- Lead sponsor
- Physicians Research And Education NetworkUniversity, hospital or other
- Study start
- Oct 2010
- Primary completion
- Jan 2013 (actual)
- Study completion
- Feb 2013 (actual)
- First posted
- 1 Jun 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.
Most individuals with major depressive disorder manifest clinically significant agitation. Concurrent agitation in a depressed individual is associated with an intensification of mood symptoms, decreased probability of recovery, increased recurrence risk, suicidality, and increased medical-service utilization. The occurrence of anxiety/agitation phenomenology in the depressed patient often invites the need for augmentation strategies (e.g. atypical antipsychotics, benzodiazepines, etc.) and complicated polypharmacy regimens. Moreover, individuals with major depressive disorder often report worsening of symptom severity, irritability, hostility, dysphoria, and significant subjective distress (This response pattern is similar to individuals with bipolar disorder).
Results from large research studies provide evidence indicating that quetiapine is capable of offering clinically significant multidimensional symptom relief in bipolar depression. Moreover, results from several trials in major depressive disorder and generalized anxiety disorder have established the efficacy of quetiapine therapy for unipolar depression and anxiety syndromes. So far, no atypical antipsychotic agent has been evaluated specifically for the treatment of agitated depression.
In this study, it is hypothesized that persons with major depressive disorder and prominent agitation (i.e. agitated depression) will exhibit a more favourable response and tolerability profile to quetiapine XR when compared to escitalopram.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Quetiapine XR | Active comparator | Drug: Quetiapine XR |
| Escitalopram | Active comparator | Drug: Escitalopram |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Male or female
- Age 18 to 65
- Outpatient at enrolment
- A diagnosis of major depressive disorder
- Baseline HAMD-17 score > 20 and HAMD Item1 score > 2 both at enrolment and baseline
Key exclusion criteria (35 listed)
- Another Axis I diagnosis of primary focus within 6 months of enrolment
- Axis II disorder causing impact on current diagnosis
- Current depressive episode <4 weeks, or >12 months
- Substance or alcohol abuse or dependency as defined by DSM IV within 6 months of enrolment
- Any pervasive developmental disorder or dementing disorder
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 |
|---|---|---|
| Quetiapine XRAlso: Seroquel XRDosage form: tablets Day 1-2: 50 mg Day 3-7: 150 mg Day 8-57: either 150 or 300 mg/day (flexible) | Drug | Quetiapine XR |
| EscitalopramDosage form: capsules Day 1-7: 10 mg Day 8-57: 10 or 20 mg/day (flexible) | Drug | Escitalopram |
Primary outcome
Change from baseline to endpoint in the Hamilton Depression Rating Scale 17-Item (HAMD-17) total score
Time frame: Day 1, Day 57
A tool to assess the range of symptoms of depression
14 secondary outcomes
Change in anxiety factor score on the Hamilton Depression Rating Scale 17-item (HAMD-17) from baseline to endpoint
Time frame: Day 1, Day 57
Change from baseline to endpoint in Hamilton Anxiety Rating Scale (HAMA) total score
Time frame: Day 1, Day 57
Change in Clinical Global Impression score from baseline to endpoint
Time frame: Screening Visit, Day 1, Day 8, Day 15, Day 29, Day 43, Day 57
Change from baseline to endpoint in Sheehan Disability Scale (SDS) sub-scales and total score
Time frame: Day 1, Day 57
Change in Hamilton Depression Rating Scale 17-item (HAMD-17) sleep disturbance factor score on the from baseline to endpoint
Time frame: Day 1, Day 57
Change in Hamilton Anxiety Rating Scale (HAMA) somatic and psychic anxiety factor scores from baseline to endpoint
Time frame: Day 1, Day 57
Change from baseline in the Sex Functioning Questionnaire (Sex FX)
Time frame: Day 1, Day 57
Change in blood pressure and heart rate from baseline to end of treatment
Time frame: Day 1, Day 57
Change in weight, BMI, waist circumference from baseline to end of treatment
Time frame: Day 1, Day 57
Change in findings from physical examination from baseline to end of treatment
Time frame: Screening, Day 57
Tabulation of spontaneous adverse events
Time frame: Day 1, Day 57
Tabulation of clinical haematology and chemistry results
Time frame: Screening, Day 57
Incidence of premature study withdrawal due to inadequate control of depressive symptoms
Proportion of patients with HAM-D Item 3 score > 2 at any time after randomization or adverse events of suicidality/suicidal ideation/suicide attempts/suicide completion
Time frame: Day 1, Day 57
Results and safety
The study was stopped early (reason given: Termination of sponsorship). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2014.
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.
Roger McIntyre, MD, FRCPC study director
Physicians Research And Education Network
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Quetiapine XR and Escitalopram in people with Depression With Prominent Agitation, run by Physicians Research And Education Network at 11 sites in Canada.
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 10 inclusion and 35 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: stopped early, as of the sponsor's last update on 8 Jan 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in Canada. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Termination of sponsorship). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline to endpoint in the Hamilton Depression Rating Scale 17-Item (HAMD-17) total score (time frame: Day 1, Day 57). 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 8 Jan 2014.