Ignite Creation Date:
2024-05-05 @ 12:05 PM
Last Modification Date:
2024-10-26 @ 9:19 AM
Study NCT ID:
NCT00232414
Status:
COMPLETED
Last Update Posted:
2013-12-10
First Post:
2005-09-30
Brief Title:
A Double-Blind Randomized Placebo Controlled Study of Quetiapine for the Treatment of Depression in Adolescents With Bipolar Disorder
Sponsor:
University of Cincinnati
Organization:
University of Cincinnati
Study Overview
Official Title:
A Double-Blind Randomized Placebo Controlled Study of Quetiapine for the Treatment of Depression in Adolescents With Bipolar Disorder
Status:
COMPLETED
Status Verified Date:
2013-12
Last Known Status:
None
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:
In this study quetiapine is being tested for the possible treatment of bipolar I disorder with an acute depressive episode in children and adolescents
We hypothesize that quetiapine will be more efficacious than placebo for the treatment of episodes of major depression associated with adolescent BP Moreover we hypothesize that quetiapine will be safe and well-tolerated compared with placebo for the treatment of depression associated with adolescent BP Based on data from the BOLDER study and other studies of atypical antipsychotics in patients with bipolar depression Calabrese et al 2004 Macfadden et al 2004 Tohen et al 2004 which in general reveal effect sizes of approximately 05 a conservative sample size calculation assuming power of 8 estimates we would need approximately 15 patients in each group to identify a statistically significant group difference in our main outcome measure change form baseline to endpoint in the Childrens Depression Rating Scale Poznanski 1979
We hypothesize that quetiapine will be more efficacious than placebo for the treatment of episodes of major depression associated with adolescent BP Moreover we hypothesize that quetiapine will be safe and well-tolerated compared with placebo for the treatment of depression associated with adolescent BP Based on data from the BOLDER study and other studies of atypical antipsychotics in patients with bipolar depression Calabrese et al 2004 Macfadden et al 2004 Tohen et al 2004 which in general reveal effect sizes of approximately 05 a conservative sample size calculation assuming power of 8 estimates we would need approximately 15 patients in each group to identify a statistically significant group difference in our main outcome measure change form baseline to endpoint in the Childrens Depression Rating Scale Poznanski 1979
Detailed Description:
This is a double-blind randomized 56-day treatment trial of quetiapine vs placebo for the treatment of bipolar adolescents with acute depression Randomization will be stratified by sex the presence of psychotic features and a site specific randomization schedule will be determined Stratification of randomization by sex is necessary to control for the higher rate of co-occurring ADHD in males than in females with bipolar disorder Bipolar disorder with ADHD may be more treatment refractory than bipolar disorder without ADHD Stratification by the presence of psychosis is necessary to avoid all patients with psychosis being assigned to one treatment group A randomization schedule will be developed by the Childrens Hospital Medical Center Investigational Pharmacy
Procedures Thirty adolescents who are hospitalized for an episode of major depression associated with BP type I ages 12-18 will be recruited for the study over two years
After providing informed consent the parent or legal guardian informed assent the child and signing the document both the parent and the child subjects will be evaluated using the Washington University at St Louis Kiddie-Schedule for Affective Disorders and Schizophrenia K-SADS Geller et al 1998 by raters with extensive training in the instrument and established inter-rater reliability ICC09 DelBello et al 2004 The WASH-U K-SADS is a semi-structured clinical interview with established validity and reliability to assess the presence of DSM-IV Axis I psychiatric disorders in children and adolescents Geller et al 1998 The K-SADS involves an interview with the child and another interview with the parent
If the diagnosis of bipolar disorder type I current episode depressed is confirmed by the K-SADS the following scales will also be performed
1 The Childrens Depression Rating Scale CDRS to assess the severity of depressive symptoms Poznanski et al 1979
2 The Young Mania Scale YMRS to assess the severity of manic symptoms Fristad et al 1992 Young et al 1978
3 The Hamilton Anxiety Rating Scale HAM-A to assess the severity of anxiety symptoms Hamilton 1959
4 The Clinical Global Impression Scale BP Version CGI-BP to quantify the childs overall baseline functioning National Institute of Mental health 1985 The CGI-BP is used by the clinician to record the severity of illness at the time of assessment The score ranges from 1 normal not at all ill to 7 among the most extremely ill patients At all visits following baseline we will also perform the CGI-BP Improvement Scale to quantify the change from baseline in overall functioning The score ranges from 1 very much improved to 7 very much worse
5 The Simpson-Angus Scale Simpson and Angus 1970 Barnes Akathisia Scale Barnes 1989 and Abnormal Involuntary Movement Scale AIMS US Department of Health 1976 to assess for extrapyramidal symptoms
Patients who received prior treatment with lithium or valproate must have serum concentrations of 04 mEqL and 50 mgL respectively before receiving quetiapine or placebo Patients treated with antipsychotics po or IM non-depot stimulants or other mood stabilizers must have a 48 hr interval without receiving these agents prior to randomization except for patients recently within one dosing interval treated with depot antipsychotics who will be excluded from this trial Patients treated with prior antidepressants must have a 7 day washout period patients treated with fluoxetine will be excluded from this trial because of its long half-life
Medication in this study will be administered in a double-blind manner Patients randomized to quetiapine will be administered beginning at day 0 a dose of 100mgday which will be titrated to 300mgday by day 3 with flexible titration to 600mgday in 100mgday increments until day 28
Patients will be evaluated by a blinded to treatment status and adverse events rater at baseline day 0 MPD prior to being randomized to placebo or quetiapine Ratings 1-4 will be done at baseline day 0 and on days 7 14 21 28 35 42 49 and 56 or termination from the study
Extrapyramidal rating scales and adverse events will be assessed on days of efficacy ratings by a different rater from the rater who is performing rating scales Adverse events will be evaluated by open-ended questions about side effects and by vital sign measures Adverse events will be monitored documented and tabulated by occurrence frequency and severity Any extrapyramidal symptoms that develop in patients will be appropriately treated via dose reduction andor administration of anticholinergic agents eg benztropine and this will be recorded Patients will receive no other psychotropic agents during the study except for lorazepam as needed for anxiety or agitation up to 4 mgd for days 0-6 2 mgd on days 7 to 14 and 1mgday on days 14-21 The doses of lorazepam administered to patients will be recorded Patients requiring other psychotropic medications will be terminated at the point at which such interventions are required Please see Table 1 for schedule of assessments and laboratory tests
Investigators will be responsible for monitoring the safety of patients who have entered this protocol and for alerting AstraZeneca to any event that seems unusual even if this event may be considered an unanticipated benefit to the patient Additionally baseline medical history physical examination laboratory tests and vital signs blood pressure pulse weight height and temperature will be performed Blood pressure and pulse will be taken after a patient has been lying down for 5 minutes supine and after standing for approximately 2 minutes standing Laboratory tests will include a urine pregnancy test and serum complete blood count CBC liver function tests LFTs thyroid stimulating hormone TSH renal profile prolactin level fasting glucose fasting lipid profile and an EKG Vital signs including Body Mass Index BMI and waist circumference will be repeated on days 7 14 21 28 35 42 49 and 56 or endpoint All other labs will be performed at baseline day 0 and day 56 or termination from the study with the exception of fasting plasma glucose fasting plasma lipid profile and complete blood count which will also be repeated at day 28 and days 0 and 56 A funduscopic and physical exam will be performed prior to and at termination of trial
If at any point during the study if a patient has a CDRS suicide item score one point higher than their baseline for any one week or a score of 3 they will be withdrawn from the study Additionally patients will be withdrawn from the study and treated as clinically indicated if they have a worsening of symptoms at day 14 or later as indicated by a CGI-I score of 6 or more at any time during the study or a minimal worsening of symptoms at day 21 or later as indicated by a CGI-I score of 5 at 2 consecutive visits starting at day 14
Additionally if at any point during the study patients has a CBC with differential that shows an Absolute Neutrophil Count ANC 10 x 10-9L we will repeat the test within 24 hours if it remains 10 x 10-9L the patient will be discontinued from the study
Patients will be discharged form the hospital when they are felt to be clinically stable as determined by their inpatient attending and treatment team in collaboration with Dr DelBello
Procedures Thirty adolescents who are hospitalized for an episode of major depression associated with BP type I ages 12-18 will be recruited for the study over two years
After providing informed consent the parent or legal guardian informed assent the child and signing the document both the parent and the child subjects will be evaluated using the Washington University at St Louis Kiddie-Schedule for Affective Disorders and Schizophrenia K-SADS Geller et al 1998 by raters with extensive training in the instrument and established inter-rater reliability ICC09 DelBello et al 2004 The WASH-U K-SADS is a semi-structured clinical interview with established validity and reliability to assess the presence of DSM-IV Axis I psychiatric disorders in children and adolescents Geller et al 1998 The K-SADS involves an interview with the child and another interview with the parent
If the diagnosis of bipolar disorder type I current episode depressed is confirmed by the K-SADS the following scales will also be performed
1 The Childrens Depression Rating Scale CDRS to assess the severity of depressive symptoms Poznanski et al 1979
2 The Young Mania Scale YMRS to assess the severity of manic symptoms Fristad et al 1992 Young et al 1978
3 The Hamilton Anxiety Rating Scale HAM-A to assess the severity of anxiety symptoms Hamilton 1959
4 The Clinical Global Impression Scale BP Version CGI-BP to quantify the childs overall baseline functioning National Institute of Mental health 1985 The CGI-BP is used by the clinician to record the severity of illness at the time of assessment The score ranges from 1 normal not at all ill to 7 among the most extremely ill patients At all visits following baseline we will also perform the CGI-BP Improvement Scale to quantify the change from baseline in overall functioning The score ranges from 1 very much improved to 7 very much worse
5 The Simpson-Angus Scale Simpson and Angus 1970 Barnes Akathisia Scale Barnes 1989 and Abnormal Involuntary Movement Scale AIMS US Department of Health 1976 to assess for extrapyramidal symptoms
Patients who received prior treatment with lithium or valproate must have serum concentrations of 04 mEqL and 50 mgL respectively before receiving quetiapine or placebo Patients treated with antipsychotics po or IM non-depot stimulants or other mood stabilizers must have a 48 hr interval without receiving these agents prior to randomization except for patients recently within one dosing interval treated with depot antipsychotics who will be excluded from this trial Patients treated with prior antidepressants must have a 7 day washout period patients treated with fluoxetine will be excluded from this trial because of its long half-life
Medication in this study will be administered in a double-blind manner Patients randomized to quetiapine will be administered beginning at day 0 a dose of 100mgday which will be titrated to 300mgday by day 3 with flexible titration to 600mgday in 100mgday increments until day 28
Patients will be evaluated by a blinded to treatment status and adverse events rater at baseline day 0 MPD prior to being randomized to placebo or quetiapine Ratings 1-4 will be done at baseline day 0 and on days 7 14 21 28 35 42 49 and 56 or termination from the study
Extrapyramidal rating scales and adverse events will be assessed on days of efficacy ratings by a different rater from the rater who is performing rating scales Adverse events will be evaluated by open-ended questions about side effects and by vital sign measures Adverse events will be monitored documented and tabulated by occurrence frequency and severity Any extrapyramidal symptoms that develop in patients will be appropriately treated via dose reduction andor administration of anticholinergic agents eg benztropine and this will be recorded Patients will receive no other psychotropic agents during the study except for lorazepam as needed for anxiety or agitation up to 4 mgd for days 0-6 2 mgd on days 7 to 14 and 1mgday on days 14-21 The doses of lorazepam administered to patients will be recorded Patients requiring other psychotropic medications will be terminated at the point at which such interventions are required Please see Table 1 for schedule of assessments and laboratory tests
Investigators will be responsible for monitoring the safety of patients who have entered this protocol and for alerting AstraZeneca to any event that seems unusual even if this event may be considered an unanticipated benefit to the patient Additionally baseline medical history physical examination laboratory tests and vital signs blood pressure pulse weight height and temperature will be performed Blood pressure and pulse will be taken after a patient has been lying down for 5 minutes supine and after standing for approximately 2 minutes standing Laboratory tests will include a urine pregnancy test and serum complete blood count CBC liver function tests LFTs thyroid stimulating hormone TSH renal profile prolactin level fasting glucose fasting lipid profile and an EKG Vital signs including Body Mass Index BMI and waist circumference will be repeated on days 7 14 21 28 35 42 49 and 56 or endpoint All other labs will be performed at baseline day 0 and day 56 or termination from the study with the exception of fasting plasma glucose fasting plasma lipid profile and complete blood count which will also be repeated at day 28 and days 0 and 56 A funduscopic and physical exam will be performed prior to and at termination of trial
If at any point during the study if a patient has a CDRS suicide item score one point higher than their baseline for any one week or a score of 3 they will be withdrawn from the study Additionally patients will be withdrawn from the study and treated as clinically indicated if they have a worsening of symptoms at day 14 or later as indicated by a CGI-I score of 6 or more at any time during the study or a minimal worsening of symptoms at day 21 or later as indicated by a CGI-I score of 5 at 2 consecutive visits starting at day 14
Additionally if at any point during the study patients has a CBC with differential that shows an Absolute Neutrophil Count ANC 10 x 10-9L we will repeat the test within 24 hours if it remains 10 x 10-9L the patient will be discontinued from the study
Patients will be discharged form the hospital when they are felt to be clinically stable as determined by their inpatient attending and treatment team in collaboration with Dr DelBello
Study Oversight
Has Oversight DMC:
None
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?:
None