Bipolar I Disorder Clinical Trial
Official title:
A Double-Blind Randomized Placebo Controlled Study of Quetiapine for the Treatment of Depression in Adolescents With Bipolar Disorder
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 0.5, 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 Children's Depression Rating Scale (Poznanski, 1979).
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 Children's 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 (ICC>0.9) (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 Children's 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 child's
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 <0.4 mEq/L and 50 mg/L 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 100mg/day which will be
titrated to 300mg/day by day 3, with flexible titration to 600mg/day (in 100mg/day
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 and/or administration of anticholinergic agents (e.g. 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 mg/d for days 0-6, 2 mg/d on days 7
to 14, and 1mg/day 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) < 1.0 x 10-9/L, we will repeat the test within 24
hours, if it remains < 1.0 x 10-9/L, 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.
;
Allocation: Randomized, Intervention Model: Single Group Assignment, Masking: Double-Blind, Primary Purpose: Treatment
Status | Clinical Trial | Phase | |
---|---|---|---|
Active, not recruiting |
NCT03641300 -
Efficacy of Convulsive Therapies for Bipolar Depression
|
N/A | |
Withdrawn |
NCT01495156 -
Study of the Efficacy of Adjunctive Lithium Treatment for the Treatment of Psychotic Mania
|
Phase 4 | |
Completed |
NCT00982020 -
Study in Adolescents With Schizophrenia or Bipolar Disorder
|
Phase 4 | |
Completed |
NCT00746343 -
Reducing Medical Risks in Individuals With Bipolar Disorder - Full Study
|
N/A | |
Completed |
NCT00177463 -
L-Carnosine for Bipolar I Disorder
|
N/A | |
Completed |
NCT03257865 -
A Trial to Assess Brexpiprazole Versus Placebo for the Treatment of Acute Manic Episodes, Associated With Bipolar I Disorder
|
Phase 3 | |
Completed |
NCT03259555 -
A Trial to Assess Brexpiprazole Versus Placebo for the Treatment of Acute Manic Episodes Associated With Bipolar I Disorder
|
Phase 3 | |
Not yet recruiting |
NCT06433635 -
Sequential Multiple Assignment Randomized Trial for Bipolar Depression
|
Phase 4 | |
Completed |
NCT04127058 -
Evaluating a New Iloperidone Titration Scheme in Bipolar I Disorder or Schizophrenia
|
Phase 1 | |
Recruiting |
NCT05977023 -
NMDA Receptor Modulation for the Treatment of Bipolar I Disorder
|
Phase 2 | |
Recruiting |
NCT05340686 -
Braining- Aerobic Physical Activity as Add on Treatment in Bipolar Depression
|
N/A | |
Completed |
NCT03287869 -
A Trial to Evaluate the Safety and Tolerability of Brexpiprazole in the Treatment of Participants With Bipolar I Disorder.
|
Phase 3 | |
Enrolling by invitation |
NCT04987229 -
Long-term Safety Extension Study of OLZ/SAM in Pediatric Subjects
|
Phase 3 | |
Completed |
NCT00761761 -
Sensoril(Ashwaganhda)for Bipolar Disorder
|
Phase 3 | |
Completed |
NCT03292848 -
Trial to Assess the Pharmacokinetics, Safety, Tolerability of Oral Brexpiprazole in Children (6 to <13 Years Old) With Central Nervous System Disorders
|
Phase 1 | |
Active, not recruiting |
NCT04561622 -
Emotional Proactive Processing in Bipolar Disorder
|
||
Recruiting |
NCT03943537 -
Effects of Intranasal Insulin on Neuroimaging Markers and Cognition in Patients With Psychotic Disorders
|
Phase 2 | |
Completed |
NCT03334721 -
Gabapentin for Bipolar & Cannabis Use Disorders
|
Phase 2 | |
Active, not recruiting |
NCT05658510 -
Dexmedetomidine in the Treatment of Agitation Associated With Schizophrenia and Bipolar Disorder (SERENITY III)
|
Phase 3 | |
Completed |
NCT00958633 -
Mood Stabilizer (MS)+ Antidepressant vs MS + Placebo in Maintenance of Bipolar Disorder.
|
Phase 3 |