- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00953745
Dopaminergic Effects of Adjunctive Aripiprazole on the Brain in Treatment-Resistant Depression
Dopaminergic Effects of Adjunctive Aripiprazole on the Brain in Treatment-Resistant Depression: A Raclopride/F-DOPA Positron Emission Tomography and Functional MRI Study
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Missouri
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Saint Louis, Missouri, United States, 63110
- Washington University in St. Louis, School of Medicine
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Treatment Group
Inclusion Criteria:
- Subjects with known history of MDD verified using the Mini International Neuropsychiatric Interview and a Hamilton Depression Rating Scale 17-item score of at least 18
- Subjects must have failed to respond to one previous adequate dose-duration trial of antidepressant therapy
- Must complete the MRI screening tool and demonstrate ability to receive an MRI
- For entry into the ARP augmentation phase the subject must be a non-responder to the escitalopram phase as demonstrated by a MADRS score at week 10, that is not reduced by greater than 50% from baseline.
Exclusion Criteria:
- Subjects cannot be smokers
- No significant history of anxiety disorder
- Cannot be pregnant or lactating and sexually active women of childbearing potential must use a medically accepted means of contraception
- The following DSM-IV diagnoses are excluded: Organic mental disorder; substance abuse/dependence, including alcohol, active within the last year; schizophrenia, paranoid or delusional disorders; other psychotic disorders; panic disorder; generalized anxiety disorder; obsessive-compulsive disorder, or post-traumatic stress disorder; bipolar disorder; bulimia nervosa; anorexia nervosa
- Subjects with serious suicidal risks
- Subjects who have taken any antidepressant medication other than escitalopram within 5 half lives, of the most recent antidepressant taken
- Subjects involved in any other form of treatment for depression
- Subjects who have demonstrated any previous inadequate antidepressant response to electroconvulsive therapy (ECT)
- Subjects who have received ECT for the current depression episode
- Subjects who have been hospitalized within 4 weeks of the study
- Subjects who have received treatment with a monoaminoxidase inhibitor within 2 weeks of enrollment
- Subjects with a known allergy, hypersensitivity, or previous unresponsiveness to aripiprazole or known intolerance to any study medications
- Subjects with a history of participation in any investigational medication trial in the past month
- A positive drug screen or substance use disorder in the past 12 months
- History of any thyroid pathology
- History of serotonin syndrome or neuroleptic malignant syndrome
- History of seizure disorder
- Subjects who have participated in a trial using PET scans in the past 12 months and in any trial in the past 30 days.
Control Group
Inclusion Criteria:
- Ages 18-55 matched to a study subject
- Must be a healthy subject with no significant medical history
- Must complete the MRI screening tool and demonstrate ability to receive an MRI
Exclusion Criteria:
- Cannot be a smoker
- Cannot be pregnant or lactating and sexually active women of childbearing potential must use a medically accepted means of contraception
- Any DSM-IV or II diagnosis as assessed by the MINI
- Subjects with a positive drug screen or substance use disorder in the past 12 months
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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 Names:
Subjects who fail to respond to Escitalopram will continue on Escitalopram and augment with active Aripiprazole.
Other Names:
All subjects will begin on escitalopram and placebo capsule for 8 weeks.
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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).
|
Week 10 and Week 16 (6 weeks of combined therapy)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
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Week 10 and Week 16 (6 weeks of combined therapy)
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Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Charles R Conway, MD, Washington University School of Medicine
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Behavioral Symptoms
- Mental Disorders
- Mood Disorders
- Depression
- Depressive Disorder
- Depressive Disorder, Major
- Depressive Disorder, Treatment-Resistant
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Antipsychotic Agents
- Tranquilizing Agents
- Psychotropic Drugs
- Serotonin Uptake Inhibitors
- Neurotransmitter Uptake Inhibitors
- Membrane Transport Modulators
- Serotonin Agents
- Antidepressive Agents
- Dopamine Agonists
- Dopamine Agents
- Serotonin 5-HT1 Receptor Agonists
- Serotonin Receptor Agonists
- Serotonin 5-HT2 Receptor Antagonists
- Serotonin Antagonists
- Dopamine D2 Receptor Antagonists
- Dopamine Antagonists
- Antidepressive Agents, Second-Generation
- Aripiprazole
- Citalopram
Other Study ID Numbers
- 201101790-2
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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