Study of Risperidone Monotherapy in Ambulatory Bipolar Disorder With Concurrent Moderately Severe Anxiety and Lifetime Panic or Generalized Anxiety Disorder
|First Submitted Date ICMJE||January 12, 2006|
|First Posted Date ICMJE||January 16, 2006|
|Last Update Posted Date||December 13, 2011|
|Start Date ICMJE||February 2004|
|Primary Completion Date||March 2009 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||Clinical Global Improvement-21 Anxiety scale (CGI-21 Anxiety) [ Time Frame: weekly ]|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT00277654 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||Hamilton Anxiety scale (HAM-A) [ Time Frame: weekly ]|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Study of Risperidone Monotherapy in Ambulatory Bipolar Disorder With Concurrent Moderately Severe Anxiety and Lifetime Panic or Generalized Anxiety Disorder|
|Official Title ICMJE||A Randomized, Double-Blind, Placebo-Controlled Study of Risperidone Monotherapy in Ambulatory Bipolar Disorder With Concurrent Moderately Severe Anxiety and Lifetime Panic or Generalized Anxiety Disorder|
|Brief Summary||The purpose of this research study is to evaluate the safety, tolerability, and efficacy (how well the drug works) of risperidone compared to placebo (an inactive drug) in the treatment of bipolar disorder with panic disorder or generalized anxiety disorder. Risperidone is currently approved by the United States Food and Drug Administration (FDA) for the treatment of schizophrenia and bipolar mania. Risperidone is not currently FDA approved for the treatment of bipolar hypomania with or without panic disorder or generalized anxiety disorder (the condition being investigated in this study).|
Methods and Procedures:
This is a randomized, double-blind, placebo controlled, parallel-group, 3 site, 8-week trial of risperidone monotherapy in outpatient subjects with a lifetime bipolar I, II, or not otherwise specified (NOS) disorder, a lifetime panic or generalized anxiety disorder, and current, at least moderately, severe anxiety symptoms. Approximately 90 subjects will be enrolled to obtain 60 subjects who complete the 8-week trial. Subjects will be randomized to risperidone or placebo in a 1:1 ratio. No concomitant psychotropic medication will be allowed except for as needed (prn) lorazepam during the first two weeks for the management of affective and anxiety symptoms, and prn zolpidem and zaleplon throughout the study for the management of insomnia. Throughout the study, psychiatric scales will be used to assess psychiatric symptoms and the presence of treatment-emergent adverse events will be monitored and recorded.
Risperidone will be administered at an initial dose of 0.5 to 1 mg/day and will be titrated upward to a dose considered optimal by the investigator based on the subject's clinical response and adverse events, but not to exceed 2.0 mg/day by the end of the second week. Subsequently, risperidone may be increased based on clinical response and tolerability to a maximum of 4.0 mg/day. As needed study-prescribed (prn) use of lorazepam will be allowed for the management of affective and anxiety symptoms for the first two weeks of the study; a maximum of 2 mg per day will be allowed during the first week, and a maximum of 1 mg per day will be allowed during the second week. During the second week, the subject must be tapered off the lorazepam. For the final six weeks of the study, no lorazepam will be permitted. Zolpidem (10-20 mg/day) or zaleplon (10-20 mg/day) will be allowed for management of insomnia, and benztropine (0.5 - 3.0 mg/day) will be allowed for management of extrapyramidal symptoms. The latter three agents will be permitted throughout the study.
From week 2 on, any medications with psychotropic effects are prohibited.
The Screening Period will last a minimum of 2 to a maximum of 30 days. At the first screening visit (Visit 0), informed consent will be obtained. The Mini International Neuropsychiatric Interview (MINI), with the Manic Module from the MINI plus, will be performed to establish whether the patient meets DSM-IV criteria for bipolar disorder I, II, or NOS, and for panic disorder or generalized anxiety disorder. For generalized anxiety disorder, the portion of Criterion F - that stipulates "the disturbance does not occur exclusively during a mood disorder" will be suspended. The CGI-BP and the CGI-S will be performed to establish the severity of bipolar affective symptoms and anxiety symptoms, respectively. Subjects will keep a mood chart in between visits to help them follow their affective and anxiety symptoms. The subject's bipolar symptoms must be evaluated as no more than moderately severe (defined as a CGI-BP < 4), and his/her anxiety symptoms must be evaluated as at least moderately severe (a CGI-S of > 4) for him/her to be able to continue in the screening process and enter the randomized phase. Medical history will be reviewed, a physical exam performed, electrocardiogram (EKG) and laboratory studies (complete metabolic profile, CBC with differential and platelets, urinalysis, pregnancy test, and urine drug screen) will be obtained. Based on these evaluations, it will be determined whether subjects meet entry criteria; subjects meeting these criteria will continue in the screening process.
Baseline Visit (last Screening Visit):
At baseline (Visit 1), subjects whose screening evaluations continue to meet all inclusion/exclusion criteria may enter the study and be randomized. These evaluations will include repeating the Clinical Global Impression modified for bipolar illness (CGI-BP) and the Clinical Global Improvement Scale for anxiety symptoms (CGI-S) to ensure the subject continues to have no more than moderately severe bipolar affective symptoms and at least moderately severe anxiety symptoms. Baseline ratings will include: the Sheehan Panic Anxiety Scale-Clinician Rated (SPAS-C); the Hamilton Anxiety Scale (HAM-A) to assess anxiety symptoms; the Young Mania Rating Scale (YMRS) to assess manic symptoms; and the Inventory for Depressive Symptoms (IDS) (long form) to assess depressive symptoms. Subjects will also be evaluated with the CGI-BP, and the Sheehan Disability Scale (SDS). The Panic-Agoraphobic Spectrum-Self-Report (PAS-SR) will be used to assess the lifetime presence of core and related features of panic disorder. (Subjects who score > 35 on the PAS-SR will be classified a-priori as having panic spectrum symptoms [PSS]). The Family Impact Scale (FIS) will be administered. The Abnormal Involuntary Movement Scale (AIMS), Simpson Angus Scale (SAS), and Barnes Akathisia Rating Scale (BARS) will be administered to assess for extrapyramidal symptoms. Blood pressure, pulse, height, and weight, will be measured. Study medication will be dispensed by the Physician Investigator in the form of 0.5 mg capsules. The dose range of risperidone will be 0.5 to 4 mg/day.
Study visits will occur every week through the eight weeks of treatment. It is expected that risperidone will be gradually increased to an optimal dose during the first month of treatment. The following procedures will be completed at each visit.
Final Evaluation (week 8) or Early Termination:
The following evaluations will be conducted at the completion of, or early withdrawal from, the 8-week treatment phase. All psychiatric evaluations and all other final study procedures (including a repeat physical exam, EKG, and laboratory studies) will be completed prior to the discontinuation of risperidone. The evaluations to be performed are:
|Study Type ICMJE||Interventional|
|Study Phase||Phase 3|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
|Intervention ICMJE||Drug: Risperidone
risperidone 0.5mg up to 4mg daily vs. placebo
Other Name: Risperidal
|Publications *||Sheehan DV, McElroy SL, Harnett-Sheehan K, Keck PE Jr, Janavs J, Rogers J, Gonzalez R, Shivakumar G, Suppes T. Randomized, placebo-controlled trial of risperidone for acute treatment of bipolar anxiety. J Affect Disord. 2009 Jun;115(3):376-85. doi: 10.1016/j.jad.2008.10.005. Epub 2008 Nov 29.|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Completion Date||March 2009|
|Primary Completion Date||March 2009 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
|Ages||18 Years and older (Adult, Senior)|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT00277654|
|Other Study ID Numbers ICMJE||RIS-PAD-402|
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||Lindner Center of HOPE|
|Study Sponsor ICMJE||Lindner Center of HOPE|
|PRS Account||Lindner Center of HOPE|
|Verification Date||December 2011|
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