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

• Sponsor: University of Pennsylvania (Other)
• Overall Status: Completed
• CT.gov ID: NCT00626340
• Collaborator: (none)
• Enrollment: 18
• Location: 1
• Arms: 4
• Duration (Months): 108
• Patients Per Site Per Month: 0.2

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Menopause; Depression	Drug: MDD diagnosis and Estrogen treatment; Drug: MDD diagnosis and Fluoxetine treatment; Drug: MDD diagnosis with both Estrogen and Fluoxetine treatment; Drug: No depression and estrogen treatment	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: Non-Randomized
• Intervention Model: Factorial Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: Jul 1, 1999
• Actual Primary Completion Date: Jul 1, 2008
• Actual Study Completion Date: Jul 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: MDD diagnosis and Estrogen treatment Menopausal women between the ages of 40-70 diagnosed with Major Depressive Disorder receiving treatment with estrogen alone.	Drug: MDD diagnosis and Estrogen treatment; 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.
Active Comparator: MDD diagnosis and Fluoxetine treatment Menopausal women between the ages of 40-70 diagnosed with Major Depressive Disorder receiving treatment with fluoxetine alone.	Drug: MDD diagnosis and Fluoxetine treatment; Menopausal women between the ages of 40-70 diagnosed with Major Depressive Disorder receiving treatment with fluoxetine alone.
Active Comparator: MDD diagnosis with both Estrogen and Fluoxetine treatment Menopausal women between the ages of 40-70 diagnosed with Major Depressive Disorder receiving treatment with estrogen and fluoxetine combined.	Drug: MDD diagnosis with both Estrogen and Fluoxetine treatment; Menopausal women between the ages of 40-70 diagnosed with Major Depressive Disorder receiving treatment with estrogen and fluoxetine combined.
Active Comparator: No depression and estrogen treatment Non-depressed menopausal women between the ages of 40-70 receiving treatment with estrogen alone.	Drug: No depression and estrogen treatment; Control participants with no MDD diagnosis received estrogen only for the treatment of physical symptoms of menopause.

Outcome Measures

Primary Outcome Measures

1. 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. [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]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 70 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yale University	New Haven	Connecticut	United States	06511

Sponsors and Collaborators

• University of Pennsylvania

Investigators

• Principal Investigator: Cynthia N Epperson, MD, University of Pennsylvania School of Medicine Department of Psychiatry

Study Documents (Full-Text)

None provided.

More Information

Publications

• Arpels JC. The female brain hypoestrogenic continuum from the premenstrual syndrome to menopause. A hypothesis and review of supporting data. J Reprod Med. 1996 Sep;41(9):633-9. Review.
• Berlanga C. Potentiating effect of estrogen in a patient with treatment-resistant depression. J Clin Psychiatry. 1988 Dec;49(12):504.
• Ditkoff EC, Crary WG, Cristo M, Lobo RA. Estrogen improves psychological function in asymptomatic postmenopausal women. Obstet Gynecol. 1991 Dec;78(6):991-5.
• Freeman EW, Purdy RH, Coutifaris C, Rickels K, Paul SM. Anxiolytic metabolites of progesterone: correlation with mood and performance measures following oral progesterone administration to healthy female volunteers. Neuroendocrinology. 1993 Oct;58(4):478-84.
• Halbreich U, Petty F, Yonkers K, Kramer GL, Rush AJ, Bibi KW. Low plasma gamma-aminobutyric acid levels during the late luteal phase of women with premenstrual dysphoric disorder. Am J Psychiatry. 1996 May;153(5):718-20.
• Krystal JH, Karper LP, Seibyl JP, Freeman GK, Delaney R, Bremner JD, Heninger GR, Bowers MB Jr, Charney DS. Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Arch Gen Psychiatry. 1994 Mar;51(3):199-214.
• López-Jaramillo P, Terán E, Molina G, Rivera J, Lozano A. Oestrogens and depression. Lancet. 1996 Jul 13;348(9020):135-6.
• Mazure C, Nelson JC, Price LH. Reliability and validity of the symptoms of major depressive illness. Arch Gen Psychiatry. 1986 May;43(5):451-6.
• Nicol-Smith L. Causality, menopause, and depression: a critical review of the literature. BMJ. 1996 Nov 16;313(7067):1229-32. Review. Erratum in: BMJ 1996 Dec 14;313(7071):1516.
• Oppenheim G. A case of rapid mood cycling with estrogen: implications for therapy. J Clin Psychiatry. 1984 Jan;45(1):34-5.
• Pariser SF. Women and mood disorders. Menarche to menopause. Ann Clin Psychiatry. 1993 Dec;5(4):249-54. Review.
• Pearlstein TB. Hormones and depression: what are the facts about premenstrual syndrome, menopause, and hormone replacement therapy? Am J Obstet Gynecol. 1995 Aug;173(2):646-53. Review.
• Petty F, Kramer GL, Gullion CM, Rush AJ. Low plasma gamma-aminobutyric acid levels in male patients with depression. Biol Psychiatry. 1992 Aug 15;32(4):354-63.
• Rothman DL, Petroff OA, Behar KL, Mattson RH. Localized 1H NMR measurements of gamma-aminobutyric acid in human brain in vivo. Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5662-6.
• Schmidt PJ, Rubinow DR. Menopause-related affective disorders: a justification for further study. Am J Psychiatry. 1991 Jul;148(7):844-52. Review.
• Schneider MA, Brotherton PL, Hailes J. The effect of exogenous oestrogens on depression in menopausal women. Med J Aust. 1977 Jul 30;2(5):162-3.
• Squires RF, Saederup E. Antidepressants and metabolites that block GABAA receptors coupled to 35S-t-butylbicyclophosphorothionate binding sites in rat brain. Brain Res. 1988 Feb 16;441(1-2):15-22.
• Steiner M. Female-specific mood disorders. Clin Obstet Gynecol. 1992 Sep;35(3):599-611. Review.
• Thomson J, Oswald I. Effect of oestrogen on the sleep, mood, and anxiety of menopausal women. Br Med J. 1977 Nov 19;2(6098):1317-9.
• Weissman MM, Klerman GL. Sex differences and the epidemiology of depression. Arch Gen Psychiatry. 1977 Jan;34(1):98-111. Review.
• Wisner KL, Wheeler SB. Prevention of recurrent postpartum major depression. Hosp Community Psychiatry. 1994 Dec;45(12):1191-6.

• Responsible Party: University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT00626340
• Other Study ID Numbers: 9907010780
• First Posted: Feb 29, 2008
• Last Update Posted: Jun 1, 2017
• Last Verified: May 1, 2017

• Keywords provided by University of Pennsylvania: menopause; women; major depressive disorder; Magnetic Resonance Spectroscopy
• Additional relevant MeSH terms: Depression; Depressive Disorder; Fluoxetine; Estrogens

Study Results

Participant Flow

Recruitment Details	Participants were recruited at an outpatient research facility located at Yale University in New Haven, CT.

Arm/Group Title	All Participants
Arm/Group 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.
Period Title: Overall Study
STARTED	18
COMPLETED	18
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group 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.
Overall Participants	0
Age (years) []
Sex: Female, Male () []
Female
Male

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

UPenn does not have access to the data collected for this study. We are only using the information entered in the protocol section for very basic details in the results section (i.e, number of participants completed). The original contact person for this protocol is not reachable.

Arm/Group Title	All Participants
Arm/Group 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.
Measure Participants	0
	0

Adverse Events

Time Frame	Entire study duration
Arm/Group Title	All Participants
Arm/Group 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.
All Cause Mortality
	All Participants
	Affected / at Risk (%)	# Events
Total	0/18 (0%)
Serious Adverse Events
	All Participants
	Affected / at Risk (%)	# Events
Total	0/18 (0%)
Other (Not Including Serious) Adverse Events
	All Participants
	Affected / at Risk (%)	# Events
Total	0/18 (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.