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Brain Imaging Study in Menopausal Women With and Without Major Depressive Disorder

Primary Purpose

Menopause, Depression

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
MDD diagnosis and Estrogen treatment
MDD diagnosis and Fluoxetine treatment
MDD diagnosis with both Estrogen and Fluoxetine treatment
No depression and estrogen treatment
Sponsored by
University of Pennsylvania
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Menopause focused on measuring menopause, women, major depressive disorder, Magnetic Resonance Spectroscopy

Eligibility Criteria

40 Years - 70 Years (Adult, Older Adult)FemaleAccepts Healthy Volunteers

Inclusion criteria for Depressed Patients:

  • Aged 40-70 years and able to give voluntary written informed consent.
  • Meet DSM-IV criteria for major depression based on a structured clinical interview (SCID).
  • Have no medical contraindication to estrogen. (This will include written documentation of a recent normal gynecological evaluation and mammogram).
  • A minimum score of 25 on the 25-item Hamilton Depression Rating Scale on initial baseline rating which does not show improvement during the one-week observation period.
  • Perimenopausal subjects will be those who have had irregular menses of either <21 days or >35 days for the previous six months to one year. Postmenopausal subjects will be those with no menstrual cycles and no hormone therapy for at least one year and serum FSH >45.

Exclusion criteria:

  • Meeting DSM-IV for any other Axis I disorder.
  • A history of serious medical or neurological illness, including (but not limited to) major cardiovascular disease, severe hypertension, intracranial mass lesions, seizure disorder, severe hepatic or renal disease, unstable endocrine or metabolic disease, and unstable hematologic disease.
  • A history of moderate to severe endometriosis; milder cases will require subject's Gynecologists permission to participate.
  • Use of anticonvulsants or benzodiazepines within the last month.
  • Use of psychotropic medication in last week (except as stated above).
  • Use of alcohol within last month.
  • Current pregnancy (for the perimenopausal subjects).
  • Positive urine drug screen.
  • Metallic implants.

Inclusion Criteria for Healthy Subjects:

  • No DSM-IV psychiatric or substance abuse diagnosis by structured diagnostic interview (SCID).
  • No medical contraindication to estrogen (this will include written documentation of a recent normal gynecological exam with mammogram).
  • Matched to depressed patients by age and menopausal status.
  • Have no menstrual cycles or hormone therapy for at least one year or irregular menses of either <21 days or 35 days for the previous six months to one year.

Exclusion Criteria for Healthy Subjects:

  • Medical, neurologic or cerebrovascular disorder (CVA, seizure disorder, etc.).
  • Evidence of substance use on urine toxicology screen done upon recruitment.
  • Current treatment with psychoactive medication.
  • Diabetes controlled by means other than diet.
  • Use of alcohol within last month.
  • Implanted metallic devices.
  • Positive urine drug screen.

Sites / Locations

  • Yale University

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Active Comparator

Active Comparator

Active Comparator

Arm Label

MDD diagnosis and Estrogen treatment

MDD diagnosis and Fluoxetine treatment

MDD diagnosis with both Estrogen and Fluoxetine treatment

No depression and estrogen treatment

Arm Description

Menopausal women between the ages of 40-70 diagnosed with Major Depressive Disorder receiving treatment with estrogen alone.

Menopausal women between the ages of 40-70 diagnosed with Major Depressive Disorder receiving treatment with fluoxetine alone.

Menopausal women between the ages of 40-70 diagnosed with Major Depressive Disorder receiving treatment with estrogen and fluoxetine combined.

Non-depressed menopausal women between the ages of 40-70 receiving treatment with estrogen alone.

Outcomes

Primary Outcome Measures

Comparison of Cortical GABA Levels in 4 Groups of Subjects Using Estrogen Alone, Fluoxetine Alone, Estrogen and Fluoxetine Combined in Pre and Post 4.0T Magnetic Resonance Spectroscopy Sessions.
This study was conducted at Yale University almost two decades ago. Our group at the University of Pennsylvania only has very basic information about this study. This includes the number of participants, which was 18, and the fact that no adverse events occurred. Staff members at the University of Pennsylvania do not have access to any additional study data. The contact person who initially entered this study protocol information is no longer at the University of Pennsylvania and we are unable to contact for additional information. We only know that 18 participants completed, but as far as we know data was never analyzed for these 18 participants.

Secondary Outcome Measures

Full Information

First Posted
February 21, 2008
Last Updated
May 25, 2017
Sponsor
University of Pennsylvania
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1. Study Identification

Unique Protocol Identification Number
NCT00626340
Brief Title
Brain Imaging Study in Menopausal Women With and Without Major Depressive Disorder
Official Title
Measurement of GABA and Neurosteroid Levels in Women With Menopausal Major Depression Before and After Treatment With Estrogen Alone, Fluoxetine Alone, or Estrogen and Fluoxetine and Normal Controls Before and After Treatment With Estrogen
Study Type
Interventional

2. Study Status

Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
July 1999 (undefined)
Primary Completion Date
July 2008 (Actual)
Study Completion Date
July 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Pennsylvania

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose this study is to measure cortical gama-aminobutyric acid levels (GABA) levels in menopausal women with major depressive disorder and healthy subjects using nuclear magnetic resonance spectroscopy (MRS). Measurements will be compared in 1) menopausal healthy subjects before and after estrogen replacement, and after fourteen days of medroxyprogesterone administration; and 2) in depressed menopausal subjects before and after treatment of their depression with antidepressant alone, estrogen alone or antidepressant plus estrogen. Cortical GABA levels will be correlated with plasma GABA and neurosteroid levels. Neurosteroids to be measured include progesterone, allopregnanolone, pregnenolone, and pregnenolone sulfate.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Menopause, Depression
Keywords
menopause, women, major depressive disorder, Magnetic Resonance Spectroscopy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Factorial Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
18 (Actual)

8. Arms, Groups, and Interventions

Arm Title
MDD diagnosis and Estrogen treatment
Arm Type
Active Comparator
Arm Description
Menopausal women between the ages of 40-70 diagnosed with Major Depressive Disorder receiving treatment with estrogen alone.
Arm Title
MDD diagnosis and Fluoxetine treatment
Arm Type
Active Comparator
Arm Description
Menopausal women between the ages of 40-70 diagnosed with Major Depressive Disorder receiving treatment with fluoxetine alone.
Arm Title
MDD diagnosis with both Estrogen and Fluoxetine treatment
Arm Type
Active Comparator
Arm Description
Menopausal women between the ages of 40-70 diagnosed with Major Depressive Disorder receiving treatment with estrogen and fluoxetine combined.
Arm Title
No depression and estrogen treatment
Arm Type
Active Comparator
Arm Description
Non-depressed menopausal women between the ages of 40-70 receiving treatment with estrogen alone.
Intervention Type
Drug
Intervention Name(s)
MDD diagnosis and Estrogen treatment
Intervention Description
Treatment for major depressive disorder occurring in the context of the menopause while participating in brain imaging sessions pre and post treatment. Women receiving treatment for depression will be compared to normal controls receiving estrogen only for physical symptoms of menopause.
Intervention Type
Drug
Intervention Name(s)
MDD diagnosis and Fluoxetine treatment
Intervention Description
Menopausal women between the ages of 40-70 diagnosed with Major Depressive Disorder receiving treatment with fluoxetine alone.
Intervention Type
Drug
Intervention Name(s)
MDD diagnosis with both Estrogen and Fluoxetine treatment
Intervention Description
Menopausal women between the ages of 40-70 diagnosed with Major Depressive Disorder receiving treatment with estrogen and fluoxetine combined.
Intervention Type
Drug
Intervention Name(s)
No depression and estrogen treatment
Intervention Description
Control participants with no MDD diagnosis received estrogen only for the treatment of physical symptoms of menopause.
Primary Outcome Measure Information:
Title
Comparison of Cortical GABA Levels in 4 Groups of Subjects Using Estrogen Alone, Fluoxetine Alone, Estrogen and Fluoxetine Combined in Pre and Post 4.0T Magnetic Resonance Spectroscopy Sessions.
Description
This study was conducted at Yale University almost two decades ago. Our group at the University of Pennsylvania only has very basic information about this study. This includes the number of participants, which was 18, and the fact that no adverse events occurred. Staff members at the University of Pennsylvania do not have access to any additional study data. The contact person who initially entered this study protocol information is no longer at the University of Pennsylvania and we are unable to contact for additional information. We only know that 18 participants completed, but as far as we know data was never analyzed for these 18 participants.
Time Frame
Healthy controls will undergo scans pre and post 3 weeks of estrogen treatment. Women with depression will undergo scans pre and post 6 weeks of treatment with estrogen alone, estrogen and fluoxetine, or fluoxetine alone

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion criteria for Depressed Patients: Aged 40-70 years and able to give voluntary written informed consent. Meet DSM-IV criteria for major depression based on a structured clinical interview (SCID). Have no medical contraindication to estrogen. (This will include written documentation of a recent normal gynecological evaluation and mammogram). A minimum score of 25 on the 25-item Hamilton Depression Rating Scale on initial baseline rating which does not show improvement during the one-week observation period. Perimenopausal subjects will be those who have had irregular menses of either <21 days or >35 days for the previous six months to one year. Postmenopausal subjects will be those with no menstrual cycles and no hormone therapy for at least one year and serum FSH >45. Exclusion criteria: Meeting DSM-IV for any other Axis I disorder. A history of serious medical or neurological illness, including (but not limited to) major cardiovascular disease, severe hypertension, intracranial mass lesions, seizure disorder, severe hepatic or renal disease, unstable endocrine or metabolic disease, and unstable hematologic disease. A history of moderate to severe endometriosis; milder cases will require subject's Gynecologists permission to participate. Use of anticonvulsants or benzodiazepines within the last month. Use of psychotropic medication in last week (except as stated above). Use of alcohol within last month. Current pregnancy (for the perimenopausal subjects). Positive urine drug screen. Metallic implants. Inclusion Criteria for Healthy Subjects: No DSM-IV psychiatric or substance abuse diagnosis by structured diagnostic interview (SCID). No medical contraindication to estrogen (this will include written documentation of a recent normal gynecological exam with mammogram). Matched to depressed patients by age and menopausal status. Have no menstrual cycles or hormone therapy for at least one year or irregular menses of either <21 days or 35 days for the previous six months to one year. Exclusion Criteria for Healthy Subjects: Medical, neurologic or cerebrovascular disorder (CVA, seizure disorder, etc.). Evidence of substance use on urine toxicology screen done upon recruitment. Current treatment with psychoactive medication. Diabetes controlled by means other than diet. Use of alcohol within last month. Implanted metallic devices. Positive urine drug screen.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Cynthia N Epperson, MD
Organizational Affiliation
University of Pennsylvania School of Medicine Department of Psychiatry
Official's Role
Principal Investigator
Facility Information:
Facility Name
Yale University
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06511
Country
United States

12. IPD Sharing Statement

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Brain Imaging Study in Menopausal Women With and Without Major Depressive Disorder

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