Effects of Cognitive Behavioral Therapy on Brain Serotonin Activity in People With Depression

• Sponsor: University of Pennsylvania (Other)
• Overall Status: Completed
• CT.gov ID: NCT00641108
• Collaborator: National Institute of Mental Health (NIMH) (NIH)
• Enrollment: 30
• Location: 1
• Arms: 2
• Duration (Months): 47
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

This study will examine changes in brain serotonin activity in people with depression before and after they receive cognitive behavioral therapy.

Condition or Disease	Intervention/Treatment	Phase
Depression	Drug: ADAM SPECT plus Cognitive Therapy; Drug: ADAM SPECT plus No Therapy	Phase 2/Phase 3

Detailed Description

Depression is a serious illness that affects almost 19 million adults in the United States each year. Common symptoms of depression include persistent feelings of anxiety, guilt, or hopelessness; irregular sleep and appetite patterns; lethargy; disinterest in previously enjoyed activities; excessive irritability and restlessness; suicidal thoughts; and inability to concentrate. A person's depression can be attributed to a variety of causes, including biological and genetic factors, environmental influences, or developmental experiences. Among biological factors, a recently researched possible cause is the altered activity of specialized areas on brain nerve cells called serotonin receptors, which have been found to be at reduced levels in people with depression. The hormone serotonin is known to naturally influence mood, making depression treatments that aim to increase levels of serotonin important. Treatment for depression with cognitive behavioral therapy (CBT), which teaches ways to modify thoughts and behaviors that contribute to depression, may help in raising brain serotonin levels and in improving depressive symptoms. This study will examine changes in brain serotonin activity using single photon emission computed tomography (SPECT) imaging in people with depression before and after they receive CBT. The study will also use SPECT imaging to compare brain serotonin activity of non-depressed healthy participants with that of depressed participants.

Participation in this study will last between 12 and 14 weeks. All participants will first undergo an initial evaluation that will include questions about medical history, a physical exam, a blood draw, a urine test, and an electrocardiogram (ECG). Participants will then undergo an ADAM (a selective radioligand for SPECT imaging) SPECT scan. During the ADAM SPECT scan visit, participants will undergo an injection of the ADAM, an ECG, blood pressure monitoring, and a 60-minute SPECT scan. If necessary, participants may also be asked to have a magnetic resonance imaging (MRI) brain scan after completing the SPECT scan.

Depressed participants will then attend at least once weekly CBT sessions for 12 weeks. During the 45-minute sessions, participants will meet with a therapist to learn ways to adjust thoughts and behaviors that may be adding to their depression. After completing the 12 weeks of CBT, all participants will be re-evaluated by a study doctor and, if still in good health, will undergo a repeat ADAM SPECT scan.

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Effect of Psychotherapy on Brain Serotonin Activity
• Study Start Date: Jan 1, 2008
• Actual Primary Completion Date: Dec 1, 2011
• Actual Study Completion Date: Dec 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ADAM SPECT Participants with depression will undergo ADAM SPECT scans and cognitive behavioral therapy.	Drug: ADAM SPECT plus Cognitive Therapy
Active Comparator: Control Healthy subjects without depression will undergo ADAM SPECT scans.	Drug: ADAM SPECT plus No Therapy

Outcome Measures

Primary Outcome Measures

1. Change in Serotonin Transporter Availability [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 disorder (MDD)

• Drug naive from prior psychotropic medication for more than 6 months before study entry

• Hamilton-Depression (HAM-D) 17 score greater than or equal to 16

• Woman of childbearing age with a negative pregnancy test within 48 hours of scanning

Exclusion Criteria:

• DSM-IV Axis I diagnosis other than MDD

• Use of psychotropic medication within 6 months of study entry

• History of bipolar disorder

• Current alcohol or drug abuse/dependence within 6 months of 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 nursing

• 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 more than 24 hours in duration)

• 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 major depressive episode

• History of normal pressure hydrocephalus

• History of cancer metastatic to the central nervous system

• History of Parkinson's or other basal ganglia disease

• History of Guillain-Barré syndrome (chronic or relapsing polyneuropathy)

• Inability to undergo an MRI scan

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Depression Research Unit - University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104-3309

Sponsors and Collaborators

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

Investigators

• Principal Investigator: Robert J. DeRubeis, PhD, University of Pennsylvania

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT00641108
• Other Study ID Numbers: R34MH077580; R34MH077580; DATR A5-ETMA
• First Posted: Mar 21, 2008
• Last Update Posted: Apr 16, 2020
• Last Verified: Apr 1, 2020

• Keywords provided by University of Pennsylvania: SPECT Brain Imaging; Cognitive Therapy; Serotonin Transporter Binding; Predictive Biomarker
• Additional relevant MeSH terms: Depression; Depressive Disorder

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	ADAM SPECT	Control
Arm/Group Description	Participants with depression will undergo ADAM SPECT scans and cognitive behavioral therapy. ADAM SPECT plus Cognitive Therapy	Healthy subjects without depression will undergo ADAM SPECT scans. ADAM SPECT plus No Therapy
Period Title: Overall Study
STARTED	0	0
COMPLETED	0	0
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	ADAM SPECT	Control	Total
Arm/Group Description	Participants with depression will undergo ADAM SPECT scans and cognitive behavioral therapy. ADAM SPECT plus Cognitive Therapy	Healthy subjects without depression will undergo ADAM SPECT scans. ADAM SPECT plus No Therapy	Total of all reporting groups
Overall Participants	0	0	0
Age, Customized (participants) []
Sex: Female, Male () []
Female
Male
Race and Ethnicity Not Collected () []
Region of Enrollment (participants) []

Outcome Measures

1. Primary Outcome

Title	Change in Serotonin Transporter Availability
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	ADAM SPECT	Control
Arm/Group Description	Participants with depression will undergo ADAM SPECT scans and cognitive behavioral therapy. ADAM SPECT plus Cognitive Therapy	Healthy subjects without depression will undergo ADAM SPECT scans. ADAM SPECT plus No Therapy
Measure Participants	0	0

Adverse Events

Time Frame	8 weeks
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	ADAM SPECT		Control
Arm/Group Description	Participants with depression will undergo ADAM SPECT scans and cognitive behavioral therapy. ADAM SPECT plus Cognitive Therapy		Healthy subjects without depression will undergo ADAM SPECT scans. ADAM SPECT plus No Therapy
All Cause Mortality
	ADAM SPECT		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Serious Adverse Events
	ADAM SPECT		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	ADAM SPECT		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

Data is unavailable due to the following extenuating circumstances: principal investigator has serious health complications preventing him from inputting data, and study team has left 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.