Back to results

Brain Imaging Techniques That Predict Antidepressant Responsiveness (WyethKolden)

Primary Purpose

Major Depressive Disorder

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Venlafaxine ERT

Fluoxetine

About this trial

This is an interventional basic science trial for Major Depressive Disorder focused on measuring Major Depressive Disorder

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Intervention Group:
- Right-handed,
- Be able to lie still on their back for about 120 minutes,
- Meet DSM-IV criteria for major depression (single or recurrent),
- Have had depressive symptoms for at least 1 month prior to screen visit,
- Must score an 18 or above on the Hamilton-D at both the initial screening visit and first fMRI scanning session,
- Able to understand and speak English.
Control Group: same as above with the exception of no diagnosis of psychiatric disorder.

Exclusion Criteria:

Any history of seizures,
Current medical disorders that might make interpretation of scan data difficult,
Diabetes requiring insulin treatment,
A serious heart disorder or subjects who have had a heart attack within the last 3 months,
Subjects who meet DSM-IV criteria for alcohol/drug abuse or dependence within the last six months,
Other current DSM-IV Axis I or Axis II diagnoses,
A personal or family history of bipolar disorder,
Current use of medication that affects central nervous system (CNS) function,
Participation in the last 30 days in a clinical study involving an investigational drug,
A subject with metallic implants, such as prostheses, shrapnel or aneurysm clip-S, or persons with electronic implants, such as cardiac pacemakers. The magnetic field generated by the MRI machine can cause a displacement or malfunctioning of these devices.
A subject who is claustrophobic,
Female subjects who are pregnant,
A subject at serious risk for suicide,
Diagnosis of cancer in the past 3 years and/or has active neoplastic disease,
Nonresponse to 2 adequate trials of antidepressant treatment,
Nonresponse to 2 adequate trials of an empirically supported psychotherapy.

Sites / Locations

University of Wisconsin Madison Psychiatry Department

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

No Intervention

Arm Label

Depressed; Venlafaxine treatment

Depressed; Fluoxetine treatment

Control

Arm Description

Currently depressed subjects; Randomized medication treatment with Venlafaxine extended release tablets (Venlafaxine ERT). Dosage 75-300mg/day for up to 6 months.

Currently depressed subjects; Randomized medication treatment with Fluoxetine tablets. Dosage 20-80mg/day for up to 6 months.

Non-psychiatric subjects with no past or current history of depression. Subjects will receive no medication

Outcomes

Primary Outcome Measures

Hamilton Depression (HAM-D) and Anxiety (HAM-A) Rating Scales

Hamilton Depression rating scale is a clinician assessment tool to measure severity of depression symptoms. Minimum score is 0 (no symptoms); maximum score is 52 (severe symptoms of depression). Hamilton Anxiety rating scale is a clinician assessment tool to measure severity of anxiety symptoms. Minimum score is 0 (no symptoms); maximum score is 56 (severe symptoms of anxiety).

Functional Magnetic Resonance Imaging (fMRI) Response to an Emotional Regulation Task.

Depressed participants were scanned while viewing a sequence of positive and negative images; they were instructed to enhance or supress their emotional response to the image or to continue to attend. To examine brain function when regulating negative affect, we created contrast maps for each participant at all 3 time points by subtracting the attend condition from the suppress condition in response to negative stimuli. Data from all 3 scan sessions were used to assess treatment-induced change in brain activity when regulating emotion. Analyses examining change using difference scores (end vs. starting points), we subtracted initial HAMD score from final HAMD score. For fMRI analyses, in a voxelwise manner, we subtracted initial negative suppress vs attend from final negative suppress vs attend. Control subjects were not depressed, repeat scans to assess change were not completed. Reported results are from BA10, one of our areas of interest.

Secondary Outcome Measures

Full Information

NCT ID

NCT00909155

First Posted

May 18, 2009

Last Updated

July 3, 2018

Sponsor

University of Wisconsin, Madison

Collaborators

Wyeth is now a wholly owned subsidiary of Pfizer

1. Study Identification

Unique Protocol Identification Number

NCT00909155

Brief Title

Brain Imaging Techniques That Predict Antidepressant Responsiveness

Acronym

WyethKolden

Official Title

Non-Invasive Brain Imaging Techniques That Predict Antidepressant Responsiveness and Provide Insights Into the Mechanism of Action of Venlafaxine ER vs. Fluoxetine

Study Type

Interventional

2. Study Status

Record Verification Date

July 2018

Overall Recruitment Status

Completed

Study Start Date

July 2002 (undefined)

Primary Completion Date

December 2009 (Actual)

Study Completion Date

December 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Wisconsin, Madison

Collaborators

Wyeth is now a wholly owned subsidiary of Pfizer

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

Do functional brain changes occur during Venlafaxine ER (extended release) versus Fluoxetine treatment and do changes in selective structures, such as the amygdala, predict treatment response?

Detailed Description

This is a single site, controlled, double-blind study of outpatients. There are two arms: Forty participants who have a current Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revised (DSM-IV-TR) diagnosis of Major Depression will be recruited. These subjects will be randomized to receive one of two antidepressant medications: Fluoxetine or Venlafaxine ER for the duration of the study. Subjects will gradually be titrated onto the medications and will be seen in the clinic up to 18 times for medication checks, to monitor side effects and depressive symptoms, including suicidal ideation. In the event of suicidal ideation, subjects will be withdrawn from the study and referred for immediate treatment. Twenty normal control subjects with no current or past DSM-IV-TR diagnosis and will receive no medication. Normal control subjects will have up to 5 visits while in the study. Subjects will contact study staff to complete a phone screen and then eligible subjects will complete a clinic screen. Subjects will then be scheduled to attend the magnetic resonance imaging (MRI) simulation visit and if subjects continue to meet entrance criteria, they will be scheduled for the first MRI. Following the first MRI, subjects in the medication conditions will begin receiving medication. All subjects will undergo 3 functional magnetic resonance imaging (fMRI)s during the study: at the beginning of the study, approximately 8 weeks and 26 weeks later. During the MRI, subjects will view slides with positive and negative emotional content. Subjects will complete various clinical interviews or rating scales assessing mood and side effects at each of the visits.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Major Depressive Disorder

Keywords

Major Depressive Disorder

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

50 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Depressed; Venlafaxine treatment

Arm Type

Active Comparator

Arm Description

Currently depressed subjects; Randomized medication treatment with Venlafaxine extended release tablets (Venlafaxine ERT). Dosage 75-300mg/day for up to 6 months.

Arm Title

Depressed; Fluoxetine treatment

Arm Type

Active Comparator

Arm Description

Currently depressed subjects; Randomized medication treatment with Fluoxetine tablets. Dosage 20-80mg/day for up to 6 months.

Arm Title

Control

Arm Type

No Intervention

Arm Description

Non-psychiatric subjects with no past or current history of depression. Subjects will receive no medication

Intervention Type

Drug

Intervention Name(s)

Venlafaxine ERT

Other Intervention Name(s)

Effexor ER

Intervention Description

Titrated to a minimum dose of 75mg. Further titration based on clinician assessment at followup visits. Intervention to continue through completion of study (180 days). Initial titration: Days 1-7: 37.5 mg; Days 7-14: 75 mg; Days 15-180: 75-300mg based on clinician assessment. Titration rate is a maximum of 75mg/7d.

Intervention Type

Drug

Intervention Name(s)

Fluoxetine

Other Intervention Name(s)

Prozac

Intervention Description

Titrated to a minimum dose of 20mg. Further titration based on clinician assessment at followup visits. Intervention to continue through completion of study (180 days). Initial titration: Days 1-7: 20mg; Days 7-14: 20mg; Days 15-180: 20-80mg based on clinician assessment. Titration rate is a maximum of 20mg/7d

Primary Outcome Measure Information:

Title

Hamilton Depression (HAM-D) and Anxiety (HAM-A) Rating Scales

Description

Time Frame

Study entry, 2 months, and at end of study (6 mos)

Title

Functional Magnetic Resonance Imaging (fMRI) Response to an Emotional Regulation Task.

Description

Time Frame

At study entry, 2 months and end of study (6 months)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Intervention Group: Right-handed, Be able to lie still on their back for about 120 minutes, Meet DSM-IV criteria for major depression (single or recurrent), Have had depressive symptoms for at least 1 month prior to screen visit, Must score an 18 or above on the Hamilton-D at both the initial screening visit and first fMRI scanning session, Able to understand and speak English. Control Group: same as above with the exception of no diagnosis of psychiatric disorder. Exclusion Criteria: Any history of seizures, Current medical disorders that might make interpretation of scan data difficult, Diabetes requiring insulin treatment, A serious heart disorder or subjects who have had a heart attack within the last 3 months, Subjects who meet DSM-IV criteria for alcohol/drug abuse or dependence within the last six months, Other current DSM-IV Axis I or Axis II diagnoses, A personal or family history of bipolar disorder, Current use of medication that affects central nervous system (CNS) function, Participation in the last 30 days in a clinical study involving an investigational drug, A subject with metallic implants, such as prostheses, shrapnel or aneurysm clip-S, or persons with electronic implants, such as cardiac pacemakers. The magnetic field generated by the MRI machine can cause a displacement or malfunctioning of these devices. A subject who is claustrophobic, Female subjects who are pregnant, A subject at serious risk for suicide, Diagnosis of cancer in the past 3 years and/or has active neoplastic disease, Nonresponse to 2 adequate trials of antidepressant treatment, Nonresponse to 2 adequate trials of an empirically supported psychotherapy.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Gregory Kolden, Ph.D.

Organizational Affiliation

University of Wisconsin Madison Psychiatry Department

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Michael Peterson, MD, Ph.D.

Organizational Affiliation

University of Wisconsin Madison Psychiatry Department

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Wisconsin Madison Psychiatry Department

City

Madison

State/Province

Wisconsin

ZIP/Postal Code

53719

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

24173657

Citation

Heller AS, Johnstone T, Peterson MJ, Kolden GG, Kalin NH, Davidson RJ. Increased prefrontal cortex activity during negative emotion regulation as a predictor of depression symptom severity trajectory over 6 months. JAMA Psychiatry. 2013 Nov;70(11):1181-9. doi: 10.1001/jamapsychiatry.2013.2430.

Results Reference

result

PubMed Identifier

23223803

Citation

Heller AS, Johnstone T, Light SN, Peterson MJ, Kolden GG, Kalin NH, Davidson RJ. Relationships between changes in sustained fronto-striatal connectivity and positive affect in major depression resulting from antidepressant treatment. Am J Psychiatry. 2013 Feb;170(2):197-206. doi: 10.1176/appi.ajp.2012.12010014.

Results Reference

result

PubMed Identifier

21867991

Citation

Light SN, Heller AS, Johnstone T, Kolden GG, Peterson MJ, Kalin NH, Davidson RJ. Reduced right ventrolateral prefrontal cortex activity while inhibiting positive affect is associated with improvement in hedonic capacity after 8 weeks of antidepressant treatment in major depressive disorder. Biol Psychiatry. 2011 Nov 15;70(10):962-8. doi: 10.1016/j.biopsych.2011.06.031. Epub 2011 Aug 25.

Results Reference

result

PubMed Identifier

20080793

Citation

Heller AS, Johnstone T, Shackman AJ, Light SN, Peterson MJ, Kolden GG, Kalin NH, Davidson RJ. Reduced capacity to sustain positive emotion in major depression reflects diminished maintenance of fronto-striatal brain activation. Proc Natl Acad Sci U S A. 2009 Dec 29;106(52):22445-50. doi: 10.1073/pnas.0910651106. Epub 2009 Dec 22.

Results Reference

result

Learn more about this trial

Brain Imaging Techniques That Predict Antidepressant Responsiveness

We'll reach out to this number within 24 hrs