Dopaminergic Effects of Adjunctive Aripiprazole on the Brain in Treatment-Resistant Depression
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|ClinicalTrials.gov Identifier: NCT00953745|
Recruitment Status : Completed
First Posted : August 6, 2009
Results First Posted : April 19, 2018
Last Update Posted : April 19, 2018
|Condition or disease||Intervention/treatment||Phase|
|Major Depressive Disorder||Drug: Escitalopram Drug: Aripiprazole Drug: Placebo Capsule Drug: Placebo Tablet||Not Applicable|
This study is designed to help understand the mechanism of action of ARP in major depressive disorder (MDD) augmentation. Subjects will undergo exposure to an existing antidepressant (Lexapro 10-20mg) for 10 weeks; subjects failing to completely respond to the monotherapy antidepressant treatment will receive augmentation with ARP for six weeks. Two placebo phases are included in which the subjects will receive one placebo along with the Lexapro for the first 6 weeks and a second placebo along with Lexapro for the next two weeks. A baseline brain imaging series (MRI and 2 PET/CT scans) will be obtained at week 10, prior to starting the aripiprazole, on subjects not responding to Lexapro. A second series of images will be obtained at the end of the six weeks of ARP augmentation. The neuroimaging will consist of fMRI, a raclopride PET scan, and a fluoro-dopa PET scan.
Ten normal control subjects will not receive any treatment. They will be age and gender matched to study subjects and undergo one set of scans (fMRI,raclopride and FOPA PET scans) to use as comparison group for quality control on a non-depressed population and not for data analysis.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||43 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||This study is designed to help understand the mechanism of action of aripiprazole in MDD augmentation. Subjects will undergo exposure to en an existing antidepressant (Lexapro 10-20mg) for 10 weeks; subjects failing to completely respond to the monotherapy antidepressant treatment will receive augmentation with aripiprazole for six weeks. We have included two placebo phases to the study in which the subjects received one placebo along with the Lexapro for the first 6 weeks and a second placebo along with Lexapro for the next two weeks (weeks 7 and 8). This double placebo design is to ensure that subjects receiving aripiprazole augmentation have a legitimate response (non-placebo) to the aripiprazole augmentation. Since the N of this study is small and a small % of patients with placebo response could skew the imaging data significantly, the use of a double placebo prior to the start of the true aripiprazole augmentation should reduce or eliminate a placebo response.|
|Official Title:||Dopaminergic Effects of Adjunctive Aripiprazole on the Brain in Treatment-Resistant Depression: A Raclopride/F-DOPA Positron Emission Tomography and Functional MRI Study|
|Study Start Date :||May 2009|
|Actual Primary Completion Date :||June 2012|
|Actual Study Completion Date :||December 2012|
Active Comparator: Depressed Participants
Subjects with treatment-resistant depression (TRD) will be administered the Hamilton Depression Rating Scale (HAM-D 17) for entry and will receive escitalopram combined with an adjunctive placebo capsule for 8 weeks.
Subjects who fail to respond will continue to receive escitalopram and additionally change to receive a placebo tablet resembling the active augmentation agent Aripiprazole (ARP) for 2 weeks.
Subjects who fail to respond to escitalopram after the 2 phase placebo treatment will enter the ARP augmentation phase of the study and will receive escitalopram augmentation with ARP.
Subjects will have 3 neuroimaging scans: F-DOPA PET, raclopride PET, and functional MRI conducted after 10 weeks of treatment and repeated after 6 weeks of ARP treatment.
All subjects will begin on escitalopram and placebo for 8 weeks
Other Name: Lexapro
Subjects who fail to respond to Escitalopram will continue on Escitalopram and augment with active Aripiprazole.
Other Name: Abilify
Drug: Placebo Capsule
All subjects will begin on escitalopram and placebo capsule for 8 weeks.
Drug: Placebo Tablet
After 8 weeks, subjects will be given a 2 week supply of escitalopram and placebo tablet.
No Intervention: Control Participants
Non-depressed, age- and sex-matched subjects without a DSM-IV Axis I diagnosis will serve as controls. They will not receive antidepressant, ARP, or any drug augmentation and will be used as quality control to compare the pre-ARP and post-ARP treatment brain images.
- Fluorodopa Uptake Values in Brain Images of Aripiprazole Augmentation Responders [ Time Frame: Week 10 and Week 16 (6 weeks of combined therapy) ]A ratio of the image derived radioactivity concentration and the whole body concentration of the injected radioactivity specifically in a cluster within the right medial caudate (see data below).
- Depression Symptom Change on The Montgomery-Åsberg Depression Rating (MADRS) Scale Between ARP Responders and Non-responders. [ Time Frame: Week 10 and Week 16 (6 weeks of combined therapy) ]Montgomery-Åsberg Depression Rating (MADRS) Scale scores compared between the 6 week Aripiprazole augmentation groups (responds vs. non-responders). Total range of the MADRS is 0 to 60, with a score of greater than 34 indicating severe depression, 20-34 indicating moderate depression, 7-19 mild depression, and 0-6 normal or absent of symptoms.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00953745
|United States, Missouri|
|Washington University in St. Louis, School of Medicine|
|Saint Louis, Missouri, United States, 63110|
|Principal Investigator:||Charles R Conway, MD||Washington University School of Medicine|