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The Role of Hormones in Postpartum Mood Disorders

Primary Purpose

Postpartum Depression

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Estradiol
Placebo
Progesterone
Sponsored by
National Institute of Mental Health (NIMH)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Postpartum Depression focused on measuring Postpartum Disorders, Mood, Hormones, GnRH Agonist, Postpartum Depression

Eligibility Criteria

18 Years - 50 Years (Adult)FemaleAccepts Healthy Volunteers

INCLUSION CRITERIA: A. Group 1: Women with a history of postpartum depression: A history of DSM-IV major depression or hypomanic/manic episode that occurred within three months of childbirth (as determined by a SCID interview); has been well for a minimum of one year; a regular menstrual cycle for at least three months; age 18-50; not pregnant, not lactating and in good medical health; medication free (including birth control pills); no history of puerperal suicide attempts or psychotic episodes requiring hospitalization. Group 2: Women with a history of Major Depressive Disorder A history of DSM-IV major depression episode(s) occurring outside of pregnancy and not within three months postpartum; has been well for a minimum of one year; a regular menstrual cycle for at least three months; age 18-50; not pregnant, not lactating and in good medical health; medication free (including birth control pills); no history of suicide attempts or psychotic episodes requiring hospitalization. Group 3; Normal Controls Controls will meet all criteria specified except they must not have any past or present Axis I diagnosis or evidence of menstrually related mood disorders. EXCLUSION CRITERIA: Patients will not be permitted to enter this protocol if they have important clinical or laboratory abnormalities including any history of the following: endometriosis; undiagnosed enlargement of the ovaries; liver disease; breast cancer; a history of blood clots in the legs or lungs; undiagnosed vaginal bleeding; porphyria; diabetes mellitus; malignant melanoma; gallbladder or pancreatic disease; heart or kidney disease; cerebrovascular disease (stroke); cigarette smoking; a history of suicide attempts or psychotic episodes requiring hospitalization; recurrent migraine headaches; pregnancy (patients will be warned not to become pregnant during the study and will be advised to employ barrier contraceptive methods; pregnancy-related medical conditions such as hyperemesis gravidarum, pretoxemia and toxemia, deep vein thrombosis (DVT) and bleeding diathesis; Any woman with a first degree relative (immediate family) with premenopausal breast cancer or breast cancer presenting in both breasts or any woman who has multiple family members (greater than three relatives) with postmenopausal breast cancer will also be excluded from participating in this protocol; Any woman meeting the Stages of Reproductive Aging Workshop Criteria (STRAW) for the perimenopause will be excluded from participation. Specifically, we will exclude any woman with an elevated plasma FSH level (greater than or equal to 14 IU/L) and with menstrual cycle variability of > 7 days different from their normal cycle length; Subjects who are unable to provide informed consent; NIMH employees and staff and their immediate family members will be excluded from the study per NIMH policy.

Sites / Locations

  • National Institutes of Health Clinical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Group 1, Hormone and Placebo Group

Group 2, Continued Replacement Group

Arm Description

8 weeks of hormonal addback plus 4 weeks of placebo

12 weeks of hormone addback

Outcomes

Primary Outcome Measures

Outcome measures will include mood, behavioral, and hormonal parameters as well as response to o-CRH.
Outcome measures will include mood, behavioral, and hormonal parameters as well as response to o-CRH.

Secondary Outcome Measures

Full Information

First Posted
November 3, 1999
Last Updated
October 18, 2023
Sponsor
National Institute of Mental Health (NIMH)
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1. Study Identification

Unique Protocol Identification Number
NCT00001481
Brief Title
The Role of Hormones in Postpartum Mood Disorders
Official Title
An Endocrine Model for Postpartum Mood Disorders
Study Type
Interventional

2. Study Status

Record Verification Date
June 27, 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 26, 1996 (Actual)
Primary Completion Date
May 13, 2025 (Anticipated)
Study Completion Date
June 13, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Mental Health (NIMH)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
Determine whether postpartum depression is triggered by the abrupt withdrawal of estrogen and progesterone. The appearance of mood and behavioral symptoms during pregnancy and the postpartum period has been extensively reported. While there has been much speculation about possible biologically based etiologies for postpartum disorders (PPD), none has ever been confirmed. Preliminary results from two related studies (protocols 90-M-0088, 92-M-0174) provide evidence that women with menstrual cycle related mood disorder, but not controls, experience mood disturbances during exogenous replacement of physiologic levels of gonadal steroids. The present protocol is designed to create a "scaled-down" hormonal milieu of pregnancy and the puerperium in order to determine whether women who have had a previous episode of postpartum major effective episode will experience differential mood and behavioral effects compared with controls and to determine whether it is the abrupt withdrawal of gonadal steroids or the prolonged exposure to gonadal steroids that is associated with mood symptoms. Supraphysiologic plasma levels of gonadal steroids will be established, maintained, and then rapidly reduced, simulating the hormonal events that occur during pregnancy and parturition. This will be accomplished by administering estradiol and progesterone to women who are pretreated with a gonadotropin releasing hormone (GnRH) agonist (Lupron). After eight weeks, administration of gonadal steroids will be stopped in one group of patients and controls, and a sudden decline in the plasma hormone levels will be precipitated. Another group will be maintained on supraphysiologic levels of estrogen and progesterone for an additional month. Outcome measures will include mood, behavioral and hormonal parameters (a separate protocol done in collaboration with NICHD).
Detailed Description
The appearance of mood and behavioral symptoms during pregnancy and the postpartum period has been extensively reported. While there has been much speculation about possible biologically based etiologies for postpartum disorders (PPD), none has ever been confirmed. Preliminary results from two related studies (protocols 90-M-0088, 92-M-0174) provide evidence that women with menstrual cycle related mood disorder, but not controls, experience mood disturbances during exogenous replacement of physiologic levels of gonadal steroids. The present protocol is designed to create a scaled-down hormonal milieu of pregnancy and the puerperium in order to determine whether women who have had a previous episode of postpartum major affective episode will experience differential mood and behavioral effects compared with controls and to determine whether it is the abrupt withdrawal of gonadal steroids or the prolonged exposure to gonadal steroids that is associated with mood symptoms. Supraphysiologic plasma levels of gonadal steroids will be established, maintained, and then rapidly reduced, simulating the hormonal events that occur during pregnancy and parturition. This will be accomplished by administering estradiol and progesterone to women who are pretreated with a gonadotropin releasing hormone (GnRH) agonist (Lupron). After eight weeks, administration of gonadal steroids will be stopped in one group of patients and controls, and a sudden decline in the plasma hormone levels will be precipitated. Another group will be maintained on supraphysiologic levels of estradiol and progesterone for an additional month. Outcome measures will include mood, behavioral, and hormonal parameters.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Postpartum Depression
Keywords
Postpartum Disorders, Mood, Hormones, GnRH Agonist, Postpartum Depression

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Non-Randomized
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Group 1, Hormone and Placebo Group
Arm Type
Placebo Comparator
Arm Description
8 weeks of hormonal addback plus 4 weeks of placebo
Arm Title
Group 2, Continued Replacement Group
Arm Type
Active Comparator
Arm Description
12 weeks of hormone addback
Intervention Type
Drug
Intervention Name(s)
Estradiol
Intervention Description
To determine whether it is abrupt withdrawal or prolonged exposure to gonadal steroids that is associated with PPD.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
To determine whether it is abrupt withdrawal or prolonged exposure to gonadal steroids that is associated with PPD.
Intervention Type
Drug
Intervention Name(s)
Progesterone
Intervention Description
To determine whether it is abrupt withdrawal or prolonged exposure to gonadal steroids that is associated with PPD.
Primary Outcome Measure Information:
Title
Outcome measures will include mood, behavioral, and hormonal parameters as well as response to o-CRH.
Description
Outcome measures will include mood, behavioral, and hormonal parameters as well as response to o-CRH.
Time Frame
ongoing

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
INCLUSION CRITERIA: A. Group 1: Women with a history of postpartum depression: A history of DSM-IV major depression or hypomanic/manic episode that occurred within three months of childbirth (as determined by a SCID interview); has been well for a minimum of one year; a regular menstrual cycle for at least three months; age 18-50; not pregnant, not lactating and in good medical health; medication free (including birth control pills); no history of puerperal suicide attempts or psychotic episodes requiring hospitalization. Group 2: Women with a history of Major Depressive Disorder A history of DSM-IV major depression episode(s) occurring outside of pregnancy and not within three months postpartum; has been well for a minimum of one year; a regular menstrual cycle for at least three months; age 18-50; not pregnant, not lactating and in good medical health; medication free (including birth control pills); no history of suicide attempts or psychotic episodes requiring hospitalization. Group 3; Normal Controls Controls will meet all criteria specified except they must not have any past or present Axis I diagnosis or evidence of menstrually related mood disorders. EXCLUSION CRITERIA: Patients will not be permitted to enter this protocol if they have important clinical or laboratory abnormalities including any history of the following: endometriosis; undiagnosed enlargement of the ovaries; liver disease; breast cancer; a history of blood clots in the legs or lungs; undiagnosed vaginal bleeding; porphyria; diabetes mellitus; malignant melanoma; gallbladder or pancreatic disease; heart or kidney disease; cerebrovascular disease (stroke); cigarette smoking; a history of suicide attempts or psychotic episodes requiring hospitalization; recurrent migraine headaches; pregnancy (patients will be warned not to become pregnant during the study and will be advised to employ barrier contraceptive methods; pregnancy-related medical conditions such as hyperemesis gravidarum, pretoxemia and toxemia, deep vein thrombosis (DVT) and bleeding diathesis; Any woman with a first degree relative (immediate family) with premenopausal breast cancer or breast cancer presenting in both breasts or any woman who has multiple family members (greater than three relatives) with postmenopausal breast cancer will also be excluded from participating in this protocol; Any woman meeting the Stages of Reproductive Aging Workshop Criteria (STRAW) for the perimenopause will be excluded from participation. Specifically, we will exclude any woman with an elevated plasma FSH level (greater than or equal to 14 IU/L) and with menstrual cycle variability of > 7 days different from their normal cycle length; Subjects who are unable to provide informed consent; NIMH employees and staff and their immediate family members will be excluded from the study per NIMH policy.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Peter J Schmidt, M.D.
Phone
(301) 496-6120
Email
peterschmidt@mail.nih.gov
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter J Schmidt, M.D.
Organizational Affiliation
National Institute of Mental Health (NIMH)
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Institutes of Health Clinical Center
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
.Data will be shared with dbGaP, BTRIS and NIMH Data Archive as determined by the Principal Investigator.
IPD Sharing Time Frame
Starting 24 months after final publication
IPD Sharing Access Criteria
Data will be shared with dbGaP, BTRIS and NIMH Data Archive as determined by the Principal Investigator.
Links:
URL
https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_1995-M-0097.html
Description
NIH Clinical Center Detailed Web Page

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The Role of Hormones in Postpartum Mood Disorders

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