Effects of Antidepressant Therapy on Brain Dopamine Transporter Activity in People With Major Depression
Primary Purpose
Depression
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
S-citalopram
Cognitive behavioral therapy (CBT)
TRODAT-1 single photon emission computed tomographic (SPECT) imaging
Sponsored by
About this trial
This is an interventional other trial for Depression focused on measuring Dopamine Transporter, Biomarker, SPECT Brain Imaging, Antidepressant Therapy
Eligibility Criteria
Inclusion Criteria:
- DSM-IV diagnosis of major depressive episode (MDE) or major depressive disorder (MDD)
- Drug free of psychotropic medication for more than 6 months before study entry
- 17-item Hamilton Depression Scale (HAM-D17) score of greater than 16
- Woman of childbearing age with a negative pregnancy test within 48 hours of study entry
- Absence of DSM-IV Axis I diagnosis as determined by Structured Clinical Interview for DSM Disorders (SCID)
Exclusion Criteria:
- DSM-IV Axis I diagnosis other than MDE
- History of mania
- Current alcohol or drug abuse, or alcohol or drug dependence within 6 months before study entry
- History of sensitivity or intolerance to s-citalopram
- Medical contraindication to the use of s-citalopram
- Unstable medical condition (e.g., angina pectoris, untreated hypertension)
- Pregnant or breastfeeding
- Woman of childbearing potential not using a medically acceptable form of birth control
- Actively suicidal or requiring hospitalization
- Requiring additional psychotropic drug therapy
- History of transient ischemic attacks
- History of cerebral infarction (including lacunar infarct with symptoms that last more than 24 hours)
- History of Binswanger's disease (or a history of hypertensive encephalopathy)
- History of intracranial hemorrhage
- History of head trauma with loss of consciousness
- History of encephalitis
- History of extended exposure to known neurotoxin (e.g., cyanide, carbon monoxide)
- Uncontrolled metabolic disorder (e.g., thyroid disease, diabetes mellitus)
- History of cognitive impairment other than MDE
- History of normal pressure hydrocephalus
- History of cancer metastatic to the central nervous system
- History of Parkinson's disease or other basal ganglia disease
- History of Guillain-Barre syndrome (chronic or relapsing polyneuropathy)
- Inability to undergo an MRI scan
- History of DSM-IV Axis I Mood Disorder
Sites / Locations
- Depression Research Unit - University of Pennsylvania
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Experimental
Active Comparator
Arm Label
1
2
3
Arm Description
Healthy participants will undergo TRODAT-1 SPECT imaging.
Participants with depression will undergo TRODAT-1 SPECT imaging and treatment with s-citalopram.
Participants with depression will undergo TRODAT-1 SPECT imaging and treatment with cognitive behavioral therapy.
Outcomes
Primary Outcome Measures
Change in Dopamine Transporter Binding
Secondary Outcome Measures
Full Information
NCT ID
NCT00655057
First Posted
April 7, 2008
Last Updated
April 3, 2020
Sponsor
University of Pennsylvania
Collaborators
National Institute of Mental Health (NIMH)
1. Study Identification
Unique Protocol Identification Number
NCT00655057
Brief Title
Effects of Antidepressant Therapy on Brain Dopamine Transporter Activity in People With Major Depression
Official Title
SPECT Brain Imaging as a Bio-Marker of Major Depression
Study Type
Interventional
2. Study Status
Record Verification Date
April 2020
Overall Recruitment Status
Completed
Study Start Date
October 2005 (undefined)
Primary Completion Date
August 2009 (Actual)
Study Completion Date
December 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Pennsylvania
Collaborators
National Institute of Mental Health (NIMH)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study will examine changes in brain dopamine transporter activity before and after antidepressant therapy.
Detailed Description
Depression is a serious psychiatric disorder that affects about 10% of the adult population in the United States in a given year. Common symptoms of depression include a persistent down mood and disinterest in previously enjoyed activities, often causing strain on work, social, and family life. A person's depression can be attributed to a variety of causes, including physiological and sociological factors. Among physiological factors, dopamine (DA), a chemical associated with feelings of happiness and pleasure, may play a key role in the onset of depression and may also be involved in the beneficial effect of antidepressant medication. Recent studies have found that people with depression have increased DA transporter (DAT) levels in a specific region of the inner brain called the striatum. The increased DAT levels might reflect alterations in central DA function. Treatment for depression with selective serotonin reuptake inhibitor (SSRI) antidepressant therapy may help in returning DAT levels to normal and in improving depressive symptoms. Using single photon emission computed tomography (SPECT) imaging, this study will examine changes in brain DAT activity in people with depression before and after they receive SSRI antidepressant therapy or cognitive behavioral therapy (CBT).
Participation in this study will last about 14 weeks and will involve participants who are healthy and depressed. All participants will first undergo baseline assessments that will include a medical history, questions about current and past health, a physical exam, a blood draw, a urine sampling, and an electrocardiogram (ECG). After completing the baseline assessments, participants will undergo a TRODAT-1 SPECT scan, which will involve an injection of TRODAT-1 (a radioactive agent to measure DA) and, after a 3-hour break, a 75-minute SPECT scan. If necessary, participants may also be asked to have a magnetic resonance imaging (MRI) brain scan after completing the SPECT scan.
Participants with depression will then be assigned randomly to undergo 12 weeks of treatment with either the antidepressant medication s-citalopram or CBT. Participants assigned to take s-citalopram will return for study visits weekly for 2 weeks, every other week for 6 weeks, and then monthly for 4 weeks. During study visits, participants will receive their medication, answer questions about depression and medication side effects, and occasionally fill out general health questionnaires. Participants receiving CBT will attend twice weekly sessions for 2 weeks and then once weekly sessions for 10 weeks. Sessions will focus on modifying thoughts and behaviors that may contribute to depression. After 12 weeks, all participants will be re-evaluated by a study doctor and, if still in good health, will undergo a repeat TRODAT-1 SPECT scan.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Depression
Keywords
Dopamine Transporter, Biomarker, SPECT Brain Imaging, Antidepressant Therapy
7. Study Design
Primary Purpose
Other
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
66 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Active Comparator
Arm Description
Healthy participants will undergo TRODAT-1 SPECT imaging.
Arm Title
2
Arm Type
Experimental
Arm Description
Participants with depression will undergo TRODAT-1 SPECT imaging and treatment with s-citalopram.
Arm Title
3
Arm Type
Active Comparator
Arm Description
Participants with depression will undergo TRODAT-1 SPECT imaging and treatment with cognitive behavioral therapy.
Intervention Type
Drug
Intervention Name(s)
S-citalopram
Intervention Description
Participants will take 10 to 30 mg of s-citalopram daily for 12 weeks.
Intervention Type
Behavioral
Intervention Name(s)
Cognitive behavioral therapy (CBT)
Intervention Description
Participants will attend twice weekly CBT sessions for 2 weeks and then once weekly sessions for 10 weeks. Sessions will focus on modifying thoughts and behaviors that may contribute to depression.
Intervention Type
Procedure
Intervention Name(s)
TRODAT-1 single photon emission computed tomographic (SPECT) imaging
Intervention Description
Participants' striatal dopamine transporter (DAT) levels will be measured using [99mTc]TRODAT-1 SPECT with magnetic resonance imaging (MRI) co-localization on two separate occasions. Participants with depression will undergo TRODAT-1 SPECT imaging immediately before and after 12 weeks of their assigned treatment. Healthy participants will undergo TRODAT-1 SPECT imaging at baseline and 12 weeks later.
Primary Outcome Measure Information:
Title
Change in Dopamine Transporter Binding
Time Frame
Measured at Weeks 0 and 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
DSM-IV diagnosis of major depressive episode (MDE) or major depressive disorder (MDD)
Drug free of psychotropic medication for more than 6 months before study entry
17-item Hamilton Depression Scale (HAM-D17) score of greater than 16
Woman of childbearing age with a negative pregnancy test within 48 hours of study entry
Absence of DSM-IV Axis I diagnosis as determined by Structured Clinical Interview for DSM Disorders (SCID)
Exclusion Criteria:
DSM-IV Axis I diagnosis other than MDE
History of mania
Current alcohol or drug abuse, or alcohol or drug dependence within 6 months before study entry
History of sensitivity or intolerance to s-citalopram
Medical contraindication to the use of s-citalopram
Unstable medical condition (e.g., angina pectoris, untreated hypertension)
Pregnant or breastfeeding
Woman of childbearing potential not using a medically acceptable form of birth control
Actively suicidal or requiring hospitalization
Requiring additional psychotropic drug therapy
History of transient ischemic attacks
History of cerebral infarction (including lacunar infarct with symptoms that last more than 24 hours)
History of Binswanger's disease (or a history of hypertensive encephalopathy)
History of intracranial hemorrhage
History of head trauma with loss of consciousness
History of encephalitis
History of extended exposure to known neurotoxin (e.g., cyanide, carbon monoxide)
Uncontrolled metabolic disorder (e.g., thyroid disease, diabetes mellitus)
History of cognitive impairment other than MDE
History of normal pressure hydrocephalus
History of cancer metastatic to the central nervous system
History of Parkinson's disease or other basal ganglia disease
History of Guillain-Barre syndrome (chronic or relapsing polyneuropathy)
Inability to undergo an MRI scan
History of DSM-IV Axis I Mood Disorder
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jay D. Amsterdam, MD
Organizational Affiliation
University of Pennsylvania
Official's Role
Principal Investigator
Facility Information:
Facility Name
Depression Research Unit - University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Effects of Antidepressant Therapy on Brain Dopamine Transporter Activity in People With Major Depression
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