NCT00909155

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?

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
50

participants targeted

Target at P25-P50 for not_applicable major-depressive-disorder

Timeline
Completed

Started Jul 2002

Longer than P75 for not_applicable major-depressive-disorder

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 1, 2002

Completed
6.9 years until next milestone

First Submitted

Initial submission to the registry

May 18, 2009

Completed
9 days until next milestone

First Posted

Study publicly available on registry

May 27, 2009

Completed
6 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2009

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2009

Completed
5 years until next milestone

Results Posted

Study results publicly available

December 15, 2014

Completed
Last Updated

August 3, 2018

Status Verified

July 1, 2018

Enrollment Period

7.4 years

First QC Date

May 18, 2009

Results QC Date

December 3, 2014

Last Update Submit

July 3, 2018

Conditions

Major Depressive Disorder

Keywords

Major Depressive Disorder

Outcome Measures

Primary Outcomes (2)

  • 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).

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

  • 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.

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

Study Arms (3)

Depressed; Venlafaxine treatment

ACTIVE COMPARATOR

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

Drug: Venlafaxine ERT

Depressed; Fluoxetine treatment

ACTIVE COMPARATOR

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

Drug: Fluoxetine

Control

NO INTERVENTION

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

Interventions

Venlafaxine ERTDRUG

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.

Also known as: Effexor ER
Depressed; Venlafaxine treatment
FluoxetineDRUG

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

Also known as: Prozac
Depressed; Fluoxetine treatment

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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,
  • +1 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Wisconsin Madison Psychiatry Department

Madison, Wisconsin, 53719, United States

Location

Related Publications (4)

  • 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.

    PMID: 24173657RESULT

  • 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.

    PMID: 23223803RESULT

  • 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.

    PMID: 21867991RESULT

  • 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.

    PMID: 20080793RESULT

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Venlafaxine HydrochlorideFluoxetine

Condition Hierarchy (Ancestors)

Depressive DisorderMood DisordersMental Disorders

Intervention Hierarchy (Ancestors)

CyclohexanolsHexanolsFatty AlcoholsAlcoholsOrganic ChemicalsPhenethylaminesEthylaminesAminesCyclohexanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsLipidsPropylamines

Limitations and Caveats

Relatively small number of subjects. Not powered statistically to determine if either treatment arm (fluoxetine or venlafaxine) is superior.

Results Point of Contact

Title
Dr. Michael Peterson
Organization
University of Wisconsin
mpeterson2@wisc.edu
608 265 8130

Study Officials

  • Gregory Kolden, Ph.D.

    University of Wisconsin Madison Psychiatry Department

    PRINCIPAL INVESTIGATOR

  • Michael Peterson, MD, Ph.D.

    University of Wisconsin Madison Psychiatry Department

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 18, 2009

First Posted

May 27, 2009

Study Start

July 1, 2002

Primary Completion

December 1, 2009

Study Completion

December 1, 2009

Last Updated

August 3, 2018

Results First Posted

December 15, 2014

Record last verified: 2018-07

Locations

US(1)