|First Submitted Date ICMJE||March 9, 2007|
|First Posted Date ICMJE||August 17, 2007|
|Last Update Posted Date||July 9, 2012|
|Start Date ICMJE||February 2007|
|Primary Completion Date||June 2008 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
|Original Primary Outcome Measures ICMJE
|Change History||Complete list of historical versions of study NCT00517985 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Duloxetine for Perimenopausal Depression|
|Official Title ICMJE||Duloxetine for Perimenopausal Depression|
|Brief Summary||Recently, antidepressants have been explored as a class of medications to treat major depression in the context of perimenopause, as well as the somatic symptoms of perimenopause (such as hot flashes). Duloxetine (Cymbalta) is one of the newer antidepressants approved for the treatment of Major Depressive Disorder (MDD). Therefore, the current study is designed to assess the efficacy of duloxetine in a sample of women who are perimenopausal and meet criteria for MDD. We will assess impact on MDD and perimenopausal symptoms.|
Over twenty percent of women will experience a major depressive episode in their lifetimes, a prevalence that reflects a greater risk than is found among men. Perimenopausal depression, postpartum depression, and unpleasant, disturbing emotional and physical symptoms that occur just before monthly menstrual periods have been shown to occur during times of fluctuating levels of estrogen and other gonadal hormones.
Perimenopause is commonly defined as a time of hormonal fluctuation that typically occurs in women 40-55 years of age with changes in menstrual patterns. It has been demonstrated that women may be at particularly high risk for depressive symptoms during perimenopause due to declining levels of estrogen. In a previous study, women at risk for postpartum depression were found to benefit from estrogen replacement therapy. However, hormone replacement therapy (HRT) has become increasingly controversial in light of the findings of the Women's Health Initiative study that determined that women who received estrogen plus progestin were slightly more likely to suffer from coronary heart disease, strokes, blood clots in the lungs, and invasive breast cancer. Since the report of these results, HRT use has declined and as an alternative treatment for depression, antidepressants have been increasingly utilized for perimenopausal women. Fluoxetine, paroxetine, and venlafaxine are members of a new class of drugs called selective serotonin reuptake inhibitors (SSRIs) and which have all been demonstrated to be beneficial in the treatment of hot flashes. Recently, a new second-generation drug, Duloxetine (Cymbalta), has also been approved for the treatment of major depression. This drug is a member of a class of compounds that are referred to as serotonin-norepinephrine reuptake inhibitors (SNRIs). The method by which Duloxetine and members of this group achieve their effect is similar to that of the other antidepressant agents that have been used. Recent studies have indicated that Duloxetine appears to provide relief for both the mood and physical components of perimenopause.
In order to continue studying the benefits of Duloxetine in subjects with perimenopause, this study is designed to enroll 20 perimenopausal women with depression in a 9-week trial. Subjects cannot be enrolled in the study if they are currently using hormone replacement therapy and all patients must meet the criteria for a major depressive episode, which will be verified by the standardized protocol for establishing depression, the Structured Clinical Interview for DSM-IV (SCID).
Subjects enrolled in the study, will undergo 7 total clinic visits during a 9-week study period. The first visit will last approximately 3 hours with all other visits taking approximately 45 minutes. During the 1st visit, medical and psychiatric history will be reviewed and blood will be drawn (approximately 3 teaspoons). Blood will be used for routine laboratory testing. Urine will also be collected for a pregnancy test.
For Major Depressive Disorder, the FDA has recommended that a total dose of 40 mg/day (20 mg taken twice a day) to 60 mg/day (given either once a day or as 30 mg twice a day) be administered without regard to meals. While a 120 mg/day dose has been shown to be safe and effective, there is no evidence that doses higher than 60 mg confer additional significant benefit, and the higher dose is clearly less well tolerated. During the current study, for a short period of time participants will receive a placebo (a pill that looks like the study drug but which does not contain any medication), although during the majority of the study, participants will be receiving the actual study medication (Duloxetine). The initial dose of Duloxetine to be given will be a 30 mg dose with the dosage increased over time to 60 mg per day. This study will be blinded, meaning that participants will not know whether they are taking placebo or the study drug. However, all subjects will receive duloxetine for the majority of the time they are enrolled in the trial. Investigators will know when subjects are receiving the placebo but in order to maintain the blinding of this study, the study staff will not be able to tell participants when they are taking placebo and when they are taking Duloxetine.
After the consent forms are read and signed, participants will undergo a Structured Clinical Interview for DSM-IV (SCID) interview. In addition, symptoms will also be rated by rating scales that include the Clinical Global Impression (CGI), the Greene Climacteric Scale (GCS) and the Hamilton Depression Rating Scale (HAM-D (17-item)). To determine functional assessment in all participants, the Global Assessment Scale (GAF) will be used. All participants will also undergo an interview that will include a psychiatric and substance use history (including collection of data regarding the use of alcohol, tobacco, and illicit substances).
Medical screening will occur in conjunction with the initial entry interview. All patients must have had a gynecologic exam within the past year and if not, study personnel will provide a referral for an exam. The investigators will review the patient's medical history. Laboratory tests will include thyroid function tests (TFTs), liver function tests (LFTs), renal panel, pregnancy tests, and complete blood count (CBC). Subjects will also complete the Greene Climacteric Scale, which is used to quantify the severity of perimenopausal symptoms.
At each of the visits, all participants will be administered the CGI, HAM-D, and GCS questionnaires/surveys in addition to The Greene Climacteric Scale, which will be used to quantify symptoms of perimenopause. Also, participants will be asked at each visit if they have missed any doses during that particular week. Each of the office visits will last approximately 45 minutes. If necessary, telephone contact with investigators is permissible and will be available 24 hours/day for emergencies.
Safety and tolerability will be assessed throughout the study. At each study visit, information on any side effects that may have occurred will be collected. In the rare event that a side effect or adverse event does occurs, participants will be able to contact any of the study's research clinicians. Emergency contact personnel will be on-call 24 hours per day, seven days per week.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 4|
|Study Design ICMJE||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Condition ICMJE||Major Depressive Disorder|
|Intervention ICMJE||Drug: Duloxetine
During the current study, for a short period of time participants will receive a placebo (a pill that looks like the study drug but which does not contain any medication), although during the majority of the study, participants will be receiving the actual study medication (Duloxetine). The initial dose of Duloxetine to be given will be a 30 mg dose with the dosage increased over time to 60 mg per day. This study will be blinded, meaning that participants will not know whether they are taking placebo or the study drug. However, all subjects will receive duloxetine for the majority of the time they are enrolled in the trial. Investigators will know when subjects are receiving the placebo but in order to maintain the blinding of this study, the study staff will not be able to tell participants when they are taking placebo and when they are taking Duloxetine.
|Study Arms||Not Provided|
|Publications *||Not Provided|
* 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||June 2008|
|Primary Completion Date||June 2008 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
|Ages||40 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||NCT00517985|
|Other Study ID Numbers ICMJE||F1JUSX026|
|Has Data Monitoring Committee||No|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||University of Arizona|
|Study Sponsor ICMJE||University of Arizona|
|Collaborators ICMJE||Eli Lilly and Company|
|PRS Account||University of Arizona|
|Verification Date||July 2012|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP