Effects of Antidepressant Therapy on Brain Dopamine Transporter Activity in People With Major Depression

• Sponsor: University of Pennsylvania (Other)
• Overall Status: Completed
• CT.gov ID: NCT00655057
• Collaborator: National Institute of Mental Health (NIMH) (NIH)
• Enrollment: 66
• Location: 1
• Arms: 3
• Duration (Months): 50
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

This study will examine changes in brain dopamine transporter activity before and after antidepressant therapy.

Condition or Disease	Intervention/Treatment	Phase
Depression	Drug: S-citalopram; Behavioral: Cognitive behavioral therapy (CBT); Procedure: TRODAT-1 single photon emission computed tomographic (SPECT) imaging	Phase 2/Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 66 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: SPECT Brain Imaging as a Bio-Marker of Major Depression
• Study Start Date: Oct 1, 2005
• Actual Primary Completion Date: Aug 1, 2009
• Actual Study Completion Date: Dec 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1 Healthy participants will undergo TRODAT-1 SPECT imaging.	Procedure: TRODAT-1 single photon emission computed tomographic (SPECT) imaging; 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.
Experimental: 2 Participants with depression will undergo TRODAT-1 SPECT imaging and treatment with s-citalopram.	Drug: S-citalopram; Participants will take 10 to 30 mg of s-citalopram daily for 12 weeks.; Procedure: TRODAT-1 single photon emission computed tomographic (SPECT) imaging; 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.
Active Comparator: 3 Participants with depression will undergo TRODAT-1 SPECT imaging and treatment with cognitive behavioral therapy.	Behavioral: Cognitive behavioral therapy (CBT); 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.; Procedure: TRODAT-1 single photon emission computed tomographic (SPECT) imaging; 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.

Outcome Measures

Primary Outcome Measures

1. Change in Dopamine Transporter Binding [Measured at Weeks 0 and 12]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Depression Research Unit - University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• University of Pennsylvania
• National Institute of Mental Health (NIMH)

Investigators

• Principal Investigator: Jay D. Amsterdam, MD, University of Pennsylvania

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT00655057
• Other Study ID Numbers: R34MH070753; R34MH070753; DATR A3-NSS
• First Posted: Apr 9, 2008
• Last Update Posted: Apr 16, 2020
• Last Verified: Apr 1, 2020

• Keywords provided by University of Pennsylvania: Dopamine Transporter; Biomarker; SPECT Brain Imaging; Antidepressant Therapy
• Additional relevant MeSH terms: Depression; Depressive Disorder; Citalopram

Study Results

Participant Flow

Pre-assignment Detail	The investigator has succumb to serious health issues which prevents him from physically inputting data in the system. The study team is no longer at the university and despite all efforts to contact them in order to enter data on the investigator's behalf, data are not available.

Arm/Group Title	Healthy Participants	Patients With Depression Without CBT	Patients With Depression: CBT and SPECT
Arm/Group Description	Healthy participants will undergo TRODAT-1 SPECT imaging. TRODAT-1 single photon emission computed tomographic (SPECT) imaging: 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.	Participants with depression will undergo TRODAT-1 SPECT imaging and treatment with s-citalopram. S-citalopram: Participants will take 10 to 30 mg of s-citalopram daily for 12 weeks. TRODAT-1 single photon emission computed tomographic (SPECT) imaging: 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.	Participants with depression will undergo TRODAT-1 SPECT imaging and treatment with cognitive behavioral therapy. Cognitive behavioral therapy (CBT): 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. TRODAT-1 single photon emission computed tomographic (SPECT) imaging: 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.
Period Title: Overall Study
STARTED	0	0	0
COMPLETED	0	0	0
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Healthy Participants	Patients With Depression Without CBT	Patients With Depression: CBT and SPECT	Total
Arm/Group Description	Healthy participants will undergo TRODAT-1 SPECT imaging. TRODAT-1 single photon emission computed tomographic (SPECT) imaging: 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.	Participants with depression will undergo TRODAT-1 SPECT imaging and treatment with s-citalopram. S-citalopram: Participants will take 10 to 30 mg of s-citalopram daily for 12 weeks. TRODAT-1 single photon emission computed tomographic (SPECT) imaging: 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.	Participants with depression will undergo TRODAT-1 SPECT imaging and treatment with cognitive behavioral therapy. Cognitive behavioral therapy (CBT): 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. TRODAT-1 single photon emission computed tomographic (SPECT) imaging: 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.	Total of all reporting groups
Overall Participants	0	0	0	0
Age, Customized (participants) []
Sex/Gender, Customized (participants) []
Race and Ethnicity Not Collected () []
Region of Enrollment (participants) []

Outcome Measures

1. Primary Outcome

Title	Change in Dopamine Transporter Binding
Time Frame	Measured at Weeks 0 and 12

Outcome Measure Data

Analysis Population Description

The investigator has succumb to serious health issues which prevents him from physically inputting data in the system. The study team is no longer at the university and despite all efforts to contact them in order to enter data on the investigator's behalf, data are not available.

Arm/Group Title	Healthy Participants	Patients With Depression Without CBT	Patients With Depression: CBT and SPECT
Arm/Group Description	Healthy participants will undergo TRODAT-1 SPECT imaging. TRODAT-1 single photon emission computed tomographic (SPECT) imaging: 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.	Participants with depression will undergo TRODAT-1 SPECT imaging and treatment with s-citalopram. S-citalopram: Participants will take 10 to 30 mg of s-citalopram daily for 12 weeks. TRODAT-1 single photon emission computed tomographic (SPECT) imaging: 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.	Participants with depression will undergo TRODAT-1 SPECT imaging and treatment with cognitive behavioral therapy. Cognitive behavioral therapy (CBT): 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. TRODAT-1 single photon emission computed tomographic (SPECT) imaging: 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.
Measure Participants	0	0	0

Adverse Events

Time Frame	4 Years
Adverse Event Reporting Description	The investigator has succumb to serious health issues which prevents him from physically inputting data in the system. The study team is no longer at the university and despite all efforts to contact them in order to enter data on the investigator's behalf, data are not available.
Arm/Group Title	Healthy Participants		Patients With Depression Without CBT		Patients With Depression: CBT and SPECT
Arm/Group Description	Healthy participants will undergo TRODAT-1 SPECT imaging. TRODAT-1 single photon emission computed tomographic (SPECT) imaging: 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.		Participants with depression will undergo TRODAT-1 SPECT imaging and treatment with s-citalopram. S-citalopram: Participants will take 10 to 30 mg of s-citalopram daily for 12 weeks. TRODAT-1 single photon emission computed tomographic (SPECT) imaging: 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.		Participants with depression will undergo TRODAT-1 SPECT imaging and treatment with cognitive behavioral therapy. Cognitive behavioral therapy (CBT): 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. TRODAT-1 single photon emission computed tomographic (SPECT) imaging: 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.
All Cause Mortality
	Healthy Participants		Patients With Depression Without CBT		Patients With Depression: CBT and SPECT
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)		0/0 (NaN)
Serious Adverse Events
	Healthy Participants		Patients With Depression Without CBT		Patients With Depression: CBT and SPECT
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Healthy Participants		Patients With Depression Without CBT		Patients With Depression: CBT and SPECT
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

Data is unavailable for the following reasons: Principal Investigator has succumb to serious health issues preventing data input, and study team is no longer with the university and is unreachable to input data.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.