Functional MRI Before and After Treatment for Depression

• Sponsor: Stanford University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00896441
• Collaborator: (none)
• Enrollment: 31
• Location: 1
• Arms: 2
• Duration (Months): 63.9
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The purpose of this study is to help us understand how depression changes brain activity and how this relates to mood, anxiety, and cognitive functions like memory. We also hope to develop a brain imaging test that will predict either before or within two weeks of starting a medicine whether the treatment will work.

Condition or Disease	Intervention/Treatment	Phase
Depression; Mood Disorders; Depressive Disorder	Drug: Citalopram	N/A

Detailed Description

You were selected as a possible participant because you are suffering from a major depressive episode, and you have not previously tried the medication used in this study to treat depression. Approximately 60 subjects will participate in this study: 30 subjects who are currently suffering from a major depressive episode and 30 subjects who have never suffered from a major depressive episode.

If you choose to participate, you will be seen at the clinic for a total of five times plus three MRI scans. You will be seen once for a screening visit. If you choose to enroll, you will return a week later for the baseline visit and again at weeks 2, 4 and 8. Around the time of week one (baseline), week 2 and week 8 you will also undergo an MRI scan of the brain.

Screening Visit: The study physician and the research study staff will first screen you for eligibility. The screening visit includes meeting with a physician for a discussion of your medical history and current medications, taking your blood pressure, and checking your weight. Women of childbearing potential will also have a urine pregnancy test. You will meet with a member of the research staff for an interview to collect information about your depression and other psychiatric symptoms you have experienced. The purpose of the interview is to confirm your diagnosis and assess the current severity of your depression. The screening visit will take approximately 2 hours.

Week 1 (baseline): If you are eligible to continue with the study, you will return to the clinic within 7 days for a baseline visit. At your baseline visit, you will complete several tests to assess your memory and concentration. These tests are being conducted because problems with memory and concentration are common in people who are depressed and the researchers want to find out if there is a difference in your memory and concentration before and after taking the study medication. We also wish to compare the results to any findings from the brain imaging. Following the baseline visit, you will begin treatment with the antidepressant citalopram. The starting dose is 20 mg once per day.

Week 1 MRI: Around the time of your week one (baseline) visit and before starting medications, you will have your first MRI.

Week 2 visit: At the end of your second week, the study physician will meet with you to assess your overall condition. Your antidepressant medication will be counted to verify that you have been taking it as prescribed. Your dose will likely not change, but it is possible that it will be increased to as much as 40 mg. If you are experiencing side effects, your dose may be decreased. We will provide you with enough medication to last until your next visit.

Week 2 MRI: Around the time of your week 2 visit you will have your second MRI.

Week 4 visit: The study physician will meet with you to assess your overall condition. Your antidepressant medication will be counted to verify that you have been taking it as prescribed. The dose may be left unchanged, increased up to a total of 40 mg daily or decreased, if you are experiencing side effects (to a minimum of 20 mg daily). You will also be asked about any other medications you have taken since your last visit. We will provide you with enough medication to last until your next visit.

Week 6 (Telephone check-in): The study physician will check in with you by telephone to assess your overall condition. The dose of the citalopram may be left unchanged, increased to a maximum of 60 mg daily or decreased (to a minimum to 20 m daily) if you are experiencing side effects.

Week 8: (End-of-study visit) In addition to the usual visit procedures, the end-of-study visit will include repeated tests of memory and concentration. The study physician will also discuss recommendations for further treatment of your depression. No study medication will be dispensed at this visit.

Week 8 MRI: Around the time of your week 8 visit you will have your third and final MRI.

Study Design

• Study Type: Interventional
• Actual Enrollment: 31 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Functional MRI Before and After Treatment for Depression
• Study Start Date: Feb 1, 2009
• Actual Primary Completion Date: Oct 1, 2013
• Actual Study Completion Date: Jun 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Depressed patients Depressed patients assigned in an open-label study of citalopram	Drug: Citalopram; Refer to Detailed Description Section for full description of intervention. Week 1 (baseline): Subject will complete several tests to assess the subject's memory and concentration. Following visit, they will begin treatment with the antidepressant citalopram. Week 1 MRI: Subject will have their first MRI. Week 2 visit: Physician will meet with they to assess the subject's overall condition. Week 2 MRI: Subject will have the subject's second MRI. Week 4 visit: The study physician will meet with the subject to assess their overall condition. Week 6 (Telephone check-in): The study physician will check in with the subject by telephone to assess the subject's overall condition. Week 8: (End-of-study visit) Subject will take repeated tests of memory and concentration. The study physician will also discuss recommendations for further treatment of the subject's depression. Week 8 MRI: Around the time of the subject's week 8 visit they will have the subject's third and final MRI.
No Intervention: Controls Healthy controls used as a comparison (no intervention) group for change in resting-state fMRI over time

Outcome Measures

Primary Outcome Measures

1. Hamilton Depression Rating Scale Percent Change From Day 0 to D56 [% change from baseline to Day 56 ( week 8)]

   Utilized the Hamilton Depression Rating Scale (HAM), 21-item version to assess depressive symptoms, with a range of 0-63. Higher scores indicate more depression. For the change score, it is Baseline less Day 56 HAM total / Baseline. Thus, larger values mean a greater decrease in the level of depression

2. Voxel-wise Changes in Resting State Functional Connectivity to the Posterior Cingulate Cortex [baseline and week 8]

   The dependent variable, measured in more than 30,000 voxels across the whole brain, was the functional connectivity between the posterior cingulate cortex seed region and each voxel. This is derived as the correlation coefficient between the blood-oxygen-level dependent (BOLD) signal timeseries in the seed region and the BOLD signal timeseries in each voxel.

Secondary Outcome Measures

1. Hamilton Anxiety Scale [% change in anxiety from Day 1 to Day 56 (week 8)]

   Hamilton Anxiety Scale (HAMA) was utilized. Scores range from 0-56, with higher scores indicating more anxiety. The change score utilized baseline and Day 56 (week 8) scores. The change scores was HAMA day 1 less Ham A day 56 / HAMA Day 1. Thus, larger numbers equal a greater reduction in anxiety.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

Patients will be aged 18-65, have no significant neurologic history, must meet DSM-IV criteria for a diagnosis of major depression and be free of antidepressant or other psychotropic medication for a minimum of two weeks before enrollment. If a subject is talking psychiatric medication he/she may be weaned off of the medication by their treating physician prior to study enrollment. Such a course of action would only be advised if the current medication was not considered to be of any benefit to the subject. In particular, if a patient is on antidepressant medication which is of benefit, we would not advise tapering off medication -- and subsequent risk of relapse -- in order to participate in the study. The same line of thinking applies to all psychiatric diagnoses and associated medications candidate subjects may be taking.

Exclusion Criteria:

1. Significant head trauma with loss of consciousness.

2. Active abuse of alcohol or illegal substances.

3. Excluded psychiatric diagnoses include: Bipolar Affective Disorder, primary psychotic disorders (Schizophrenia, Schizoaffective disorder), Obsessive-Compulsive Disorder

4. Pregnant or nursing women.

5. Any contraindication to being scanned in the 3T scanner at the Lucas Center such as having a pacemaker or any implanted device that has not been cleared for scanning at 3 Tesla.

6. Any significant neurologic history (i.e. seizure, stroke, multiple sclerosis).

7. Use of psychotropic medications within 2 weeks of enrollment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University School of Medicine	Stanford	California	United States	94305

Sponsors and Collaborators

• Stanford University

Investigators

• Principal Investigator: Michael D Greicius, Stanford University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jennifer Keller, Clinical Associate Professor, Stanford University
• ClinicalTrials.gov Identifier: NCT00896441
• Other Study ID Numbers: SU-04202009-2339; Stanford IRB #15305
• First Posted: May 11, 2009
• Last Update Posted: Oct 13, 2017
• Last Verified: Sep 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Disease; Depression; Depressive Disorder; Mood Disorders; Citalopram

Study Results

Participant Flow

Pre-assignment Detail	5 participants in the Healthy controls group withdrew consent prior to allocation to study arm.

Arm/Group Title	Depressed	Healthy Controls
Arm/Group Description	Depressed individuals	Participants with no history of psychiatric illness
Period Title: Overall Study
STARTED	17	9
COMPLETED	15	9
NOT COMPLETED	2	0

Baseline Characteristics

Arm/Group Title	Depressed	Healthy Controls	Total
Arm/Group Description	Depressed individuals	Participants with no history of psychiatric illness	Total of all reporting groups
Overall Participants	15	9	24
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	40.00 (12.6)	31.92 (11.2)	36.50 (12.6)
Sex: Female, Male (Count of Participants)
Female	11 73.3%	3 33.3%	14 58.3%
Male	4 26.7%	6 66.7%	10 41.7%

Outcome Measures

1. Primary Outcome

Title	Hamilton Depression Rating Scale Percent Change From Day 0 to D56
Description	Utilized the Hamilton Depression Rating Scale (HAM), 21-item version to assess depressive symptoms, with a range of 0-63. Higher scores indicate more depression. For the change score, it is Baseline less Day 56 HAM total / Baseline. Thus, larger values mean a greater decrease in the level of depression
Time Frame	% change from baseline to Day 56 ( week 8)

Outcome Measure Data

Analysis Population Description

Only participants completing the protocol are included in the analysis; thus, the N = 12. Only participants in the Depressed group were analyzed for change in depressive symptoms.

Arm/Group Title	Depressed
Arm/Group Description	Depressed individuals
Measure Participants	12
Mean (Standard Deviation) [percentage of change in depression]	.4125 (.26)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Depressed
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.01
	Comments
	Method	t-test, 2 sided
	Comments	One sample t-test

2. Primary Outcome

Title	Voxel-wise Changes in Resting State Functional Connectivity to the Posterior Cingulate Cortex
Description	The dependent variable, measured in more than 30,000 voxels across the whole brain, was the functional connectivity between the posterior cingulate cortex seed region and each voxel. This is derived as the correlation coefficient between the blood-oxygen-level dependent (BOLD) signal timeseries in the seed region and the BOLD signal timeseries in each voxel.
Time Frame	baseline and week 8

Outcome Measure Data

Analysis Population Description

Owing to the limited sample size, we first examined this measure in the depressed subjects using a paired-sample t-test at each of the 30,000+ voxels. No significant voxels were detected in this analysis and so subsequent analyses combining the depressed subjects and the healthy control subjects in a single model were not performed.

Arm/Group Title	Depressed
Arm/Group Description	Depressed individuals
Measure Participants	13
Number [significant voxels]	0

3. Secondary Outcome

Title	Hamilton Anxiety Scale
Description	Hamilton Anxiety Scale (HAMA) was utilized. Scores range from 0-56, with higher scores indicating more anxiety. The change score utilized baseline and Day 56 (week 8) scores. The change scores was HAMA day 1 less Ham A day 56 / HAMA Day 1. Thus, larger numbers equal a greater reduction in anxiety.
Time Frame	% change in anxiety from Day 1 to Day 56 (week 8)

Outcome Measure Data

Analysis Population Description

Only participants completing the protocol are included in the analysis. Only participants in the Depressed group were analyzed for change in anxiety symptoms.

Arm/Group Title	Depressed
Arm/Group Description	Depressed individuals
Measure Participants	12
Mean (Standard Deviation) [percentage of change in anxiety]	.3988 (.43)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Depressed
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<.006
	Comments
	Method	t-test, 2 sided
	Comments	Single group t-test

Adverse Events

Arm/Group Title	Depressed		Healthy Controls
Arm/Group Description	Depressed individuals		Participants with no history of psychiatric illness
All Cause Mortality
	Depressed		Healthy Controls
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Depressed		Healthy Controls
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/17 (0%)		0/9 (0%)
Other (Not Including Serious) Adverse Events
	Depressed		Healthy Controls
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/17 (0%)		0/9 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.