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Trial record 13 of 49 for:    Postpartum Depression AND PPD | "Depression" AND "Depression"

Neurophysiology of Postpartum Depression in an Experimental Model of Pregnancy and Parturition

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ClinicalTrials.gov Identifier: NCT01762943
Recruitment Status : Completed
First Posted : January 8, 2013
Results First Posted : October 17, 2017
Last Update Posted : November 20, 2017
Sponsor:
Collaborators:
Foundation of Hope, North Carolina
North Carolina Translational and Clinical Sciences Institute
National Institutes of Health (NIH)
National Alliance for Research on Schizophrenia and Depression
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
University of North Carolina, Chapel Hill

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Basic Science
Condition Postpartum Depression
Interventions Drug: Leuprolide Acetate
Drug: Micronized estradiol
Drug: Progesterone
Enrollment 36

Recruitment Details Out of 3,341 completed screening forms, 406 women appeared initially eligible. 54 were responsive, interested in participating, and eligible to enroll based on pre-screening (unmedicated, without current psychiatric illness or chronic health conditions).
Pre-assignment Details Of the 54 women who were recruited to participate, 18 did not meet our eligibility criteria during the extensive safety screening phase because of medical conditions found upon exam, use of medications, family history of reproductive cancer, history of pregnancy-related medical condition, and lack of compliance with the screening protocol.
Arm/Group Title Women With Postpartum Depression (PPD) Women Without Any Psychiatric History (Control)
Hide Arm/Group Description

4 monthly intramuscular (IM) injections of leuprolide acetate (Lupron) 3.75 mg; micronized estradiol will be started at a dose of 4 mg/day and increased progressively up to 10 mg/day; progesterone will be started at 400 mg/day and increased progressively up to 800 mg/day. Participants will also receive placebo.

Leuprolide Acetate: All subjects will receive one IM injection (3.75 mg) each month for four months.

Micronized estradiol: All participants will receive micronized estradiol daily for eight weeks. Estradiol will be started at a dose of 4 mg/day and increased progressively up to 10 mg/day.

Progesterone: All subjects will receive micronized progesterone daily for eight weeks. Progesterone will be started at 400 mg/day and increased progressively up to 800 mg/day.

4 monthly IM injections of leuprolide acetate (Lupron) 3.75 mg; micronized estradiol will be started at a dose of 4 mg/day and increased progressively up to 10 mg/day; progesterone will be started at 400 mg/day and increased progressively up to 800 mg/day. Participants will also receive placebo.

Leuprolide Acetate: All subjects will receive one IM injection (3.75 mg) each month for four months.

Micronized estradiol: All participants will receive micronized estradiol daily for eight weeks. Estradiol will be started at a dose of 4 mg/day and increased progressively up to 10 mg/day.

Progesterone: All subjects will receive micronized progesterone daily for eight weeks. Progesterone will be started at 400 mg/day and increased progressively up to 800 mg/day.

Period Title: Overall Study
Started 19 17
Hypogonadism 18 15
Addback 16 15
Withdrawal 15 15
Completed 15 15
Not Completed 4 2
Reason Not Completed
Physician Decision             1             1
Protocol Violation             1             0
Withdrawal by Subject             2             1
Arm/Group Title Women With Postpartum Depression (PPD) Women Without Any Psychiatric History (Control) Total
Hide Arm/Group Description

4 monthly IM injections of leuprolide acetate (Lupron) 3.75 mg; micronized estradiol will be started at a dose of 4 mg/day and increased progressively up to 10 mg/day; progesterone will be started at 400 mg/day and increased progressively up to 800 mg/day. Participants will also receive placebo.

Leuprolide Acetate: All subjects will receive one IM injection (3.75 mg) each month for four months.

Micronized estradiol: All participants will receive micronized estradiol daily for eight weeks. Estradiol will be started at a dose of 4 mg/day and increased progressively up to 10 mg/day.

Progesterone: All subjects will receive micronized progesterone daily for eight weeks. Progesterone will be started at 400 mg/day and increased progressively up to 800 mg/day.

4 monthly IM injections of leuprolide acetate (Lupron) 3.75 mg; micronized estradiol will be started at a dose of 4 mg/day and increased progressively up to 10 mg/day; progesterone will be started at 400 mg/day and increased progressively up to 800 mg/day. Participants will also receive placebo.

Leuprolide Acetate: All subjects will receive one IM injection (3.75 mg) each month for four months.

Micronized estradiol: All participants will receive micronized estradiol daily for eight weeks. Estradiol will be started at a dose of 4 mg/day and increased progressively up to 10 mg/day.

Progesterone: All subjects will receive micronized progesterone daily for eight weeks. Progesterone will be started at 400 mg/day and increased progressively up to 800 mg/day.

Total of all reporting groups
Overall Number of Baseline Participants 19 17 36
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 17 participants 36 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
19
 100.0%
17
 100.0%
36
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 19 participants 17 participants 36 participants
35.053  (4.916) 36.294  (4.224) 35.639  (4.580)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 17 participants 36 participants
Female
19
 100.0%
17
 100.0%
36
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 17 participants 36 participants
Hispanic or Latino
2
  10.5%
0
   0.0%
2
   5.6%
Not Hispanic or Latino
16
  84.2%
17
 100.0%
33
  91.7%
Unknown or Not Reported
1
   5.3%
0
   0.0%
1
   2.8%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 17 participants 36 participants
American Indian or Alaska Native
2
  10.5%
0
   0.0%
2
   5.6%
Asian
0
   0.0%
3
  17.6%
3
   8.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
3
  15.8%
3
  17.6%
6
  16.7%
White
14
  73.7%
11
  64.7%
25
  69.4%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 19 participants 17 participants 36 participants
19
 100.0%
17
 100.0%
36
 100.0%
1.Primary Outcome
Title Blood-oxygen-level-dependent (BOLD) Response During Functional Magnetic Resonance Imaging (fMRI) z Statistic
Hide Description The primary outcome measure was functional magnetic resonance imaging (fMRI) data collected during a Monetary Incentive Delay (MID) Task. The BOLD response was examined within the nucleus accumbens, a brain region that responds to monetary rewards. The z statistic represents the maximum contrast between win versus non-win outcomes during the MID task in the nucleus accumbens, averaged across the participants in each group. The mean BOLD response ranged from z=1.7 to 2.3; higher z scores indicate greater activation of the nucleus accumbens during reward. Individual z scores were generated using the Oxford Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB) software library (FSL), which is a library of brain imaging analysis tools for fMRI.
Time Frame baseline and hormone withdrawal
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Of the 36 women who enrolled in the study, 6 were withdrawn prior to the second fMRI session. For the purpose of this group x time analysis, their data have been excluded. In addition, one participant had significant motion artifact (>4mm) during one run of the MID, and as such, her data were excluded from the analyses.
Arm/Group Title Women With a History of Postpartum Depression (PPD) Women Without Any Psychiatric History (Control)
Hide Arm/Group Description:

4 monthly IM injections of leuprolide acetate (Lupron) 3.75 mg; micronized estradiol will be started at a dose of 4 mg/day and increased progressively up to 10 mg/day; progesterone will be started at 400 mg/day and increased progressively up to 800 mg/day. Participants will also receive placebo.

Leuprolide Acetate: All subjects will receive one IM injection (3.75 mg) each month for four months.

Micronized estradiol: All participants will receive micronized estradiol daily for eight weeks. Estradiol will be started at a dose of 4 mg/day and increased progressively up to 10 mg/day.

Progesterone: All subjects will receive micronized progesterone daily for eight weeks. Progesterone will be started at 400 mg/day and increased progressively up to 800 mg/day.

4 monthly IM injections of leuprolide acetate (Lupron) 3.75 mg; micronized estradiol will be started at a dose of 4 mg/day and increased progressively up to 10 mg/day; progesterone will be started at 400 mg/day and increased progressively up to 800 mg/day. Participants will also receive placebo.

Leuprolide Acetate: All subjects will receive one IM injection (3.75 mg) each month for four months.

Micronized estradiol: All participants will receive micronized estradiol daily for eight weeks. Estradiol will be started at a dose of 4 mg/day and increased progressively up to 10 mg/day.

Progesterone: All subjects will receive micronized progesterone daily for eight weeks. Progesterone will be started at 400 mg/day and increased progressively up to 800 mg/day.

Overall Number of Participants Analyzed 14 15
Mean (Standard Deviation)
Unit of Measure: z score
Left Nucleus Acc Baseline 2.3  (1.13) 2.0  (.99)
Left Nucleus Acc Withdrawal 2.1  (1.20) 1.7  (.69)
Right Nucleus Acc Baseline 2.2  (1.12) 2.0  (1.09)
Right Nucleus Acc Withdrawal 2.3  (1.05) 2.0  (.83)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Women With a History of Postpartum Depression (PPD), Women Without Any Psychiatric History (Control)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .27
Comments [Not Specified]
Method repeated measures ANOVA
Comments F=1.40, df=2,26
2.Secondary Outcome
Title Change in Inventory of Depression and Anxiety Symptoms (IDAS) Dysphoria Score
Hide Description The IDAS Dysphoria Scale consists of 10 items and uses a 5-point Likert-type scale, ranging from 1 to 5 with 1 indicating "not at all" and 5 indicating "extremely". As such, the range of possible scores is 10 to 50. The Dysphoria scale includes items assessing feelings of depression, inadequacy, psychomotor agitation, guilt, discouragement, anhedonia, poor concentration, difficulty with decision-making, psychomotor retardation, and worry. Higher scores indicate greater dysphoria.
Time Frame Assessed at baseline and post-treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Of the 36 women who enrolled in the study, 6 (4 PPD, 2 controls) were withdrawn prior to the second fMRI session. For the purpose of this group x time analysis, their data have been excluded. All 30 subjects who completed the protocol were included in this analysis.
Arm/Group Title Women With a History of Postpartum Depression (PPD) Women Without Any Psychiatric History (Control)
Hide Arm/Group Description:

4 monthly IM injections of leuprolide acetate (Lupron) 3.75 mg; micronized estradiol will be started at a dose of 4 mg/day and increased progressively up to 10 mg/day; progesterone will be started at 400 mg/day and increased progressively up to 800 mg/day. Participants will also receive placebo.

Leuprolide Acetate: All subjects will receive one IM injection (3.75 mg) each month for four months.

Micronized estradiol: All participants will receive micronized estradiol daily for eight weeks. Estradiol will be started at a dose of 4 mg/day and increased progressively up to 10 mg/day.

Progesterone: All subjects will receive micronized progesterone daily for eight weeks. Progesterone will be started at 400 mg/day and increased progressively up to 800 mg/day.

4 monthly IM injections of leuprolide acetate (Lupron) 3.75 mg; micronized estradiol will be started at a dose of 4 mg/day and increased progressively up to 10 mg/day; progesterone will be started at 400 mg/day and increased progressively up to 800 mg/day. Participants will also receive placebo.

Leuprolide Acetate: All subjects will receive one IM injection (3.75 mg) each month for four months.

Micronized estradiol: All participants will receive micronized estradiol daily for eight weeks. Estradiol will be started at a dose of 4 mg/day and increased progressively up to 10 mg/day.

Progesterone: All subjects will receive micronized progesterone daily for eight weeks. Progesterone will be started at 400 mg/day and increased progressively up to 800 mg/day.

Overall Number of Participants Analyzed 15 15
Mean (Standard Deviation)
Unit of Measure: units on a scale
IDAS Dysphoria Baseline 11.4  (2.20) 12.7  (3.08)
IDAS Dysphoria Withdrawal 15.7  (8.29) 11.1  (1.34)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Women With a History of Postpartum Depression (PPD), Women Without Any Psychiatric History (Control)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .018
Comments [Not Specified]
Method repeated measures ANOVA
Comments F=6.29, df=1,28
Time Frame Adverse event data were collected for every participant over the course of the 7-month-long protocol.
Adverse Event Reporting Description Participants were asked about side effects at every study visit.
 
Arm/Group Title Women With Postpartum Depression (PPD) Women Without Any Psychiatric History (Control)
Hide Arm/Group Description

4 monthly IM injections of leuprolide acetate (Lupron) 3.75 mg; micronized estradiol will be started at a dose of 4 mg/day and increased progressively up to 10 mg/day; progesterone will be started at 400 mg/day and increased progressively up to 800 mg/day. Participants will also receive placebo.

Leuprolide Acetate: All subjects will receive one IM injection (3.75 mg) each month for four months.

Micronized estradiol: All participants will receive micronized estradiol daily for eight weeks. Estradiol will be started at a dose of 4 mg/day and increased progressively up to 10 mg/day.

Progesterone: All subjects will receive micronized progesterone daily for eight weeks. Progesterone will be started at 400 mg/day and increased progressively up to 800 mg/day.

4 monthly IM injections of leuprolide acetate (Lupron) 3.75 mg; micronized estradiol will be started at a dose of 4 mg/day and increased progressively up to 10 mg/day; progesterone will be started at 400 mg/day and increased progressively up to 800 mg/day. Participants will also receive placebo.

Leuprolide Acetate: All subjects will receive one IM injection (3.75 mg) each month for four months.

Micronized estradiol: All participants will receive micronized estradiol daily for eight weeks. Estradiol will be started at a dose of 4 mg/day and increased progressively up to 10 mg/day.

Progesterone: All subjects will receive micronized progesterone daily for eight weeks. Progesterone will be started at 400 mg/day and increased progressively up to 800 mg/day.

All-Cause Mortality
Women With Postpartum Depression (PPD) Women Without Any Psychiatric History (Control)
Affected / at Risk (%) Affected / at Risk (%)
Total   0/19 (0.00%)   0/17 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Women With Postpartum Depression (PPD) Women Without Any Psychiatric History (Control)
Affected / at Risk (%) Affected / at Risk (%)
Total   0/19 (0.00%)   0/17 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Women With Postpartum Depression (PPD) Women Without Any Psychiatric History (Control)
Affected / at Risk (%) Affected / at Risk (%)
Total   12/19 (63.16%)   11/17 (64.71%) 
Cardiac disorders     
Bradycardia or Arrhythmia   1/19 (5.26%)  1/17 (5.88%) 
Chest pain   2/19 (10.53%)  0/17 (0.00%) 
Gastrointestinal disorders     
Nausea and/or vomiting   2/19 (10.53%)  1/17 (5.88%) 
Diarrhea   1/19 (5.26%)  0/17 (0.00%) 
Constipation   0/19 (0.00%)  2/17 (11.76%) 
Heartburn or reflux   0/19 (0.00%)  1/17 (5.88%) 
General disorders     
Fatigue   6/19 (31.58%)  6/17 (35.29%) 
Weight gain   0/19 (0.00%)  1/17 (5.88%) 
Musculoskeletal and connective tissue disorders     
Back pain   1/19 (5.26%)  0/17 (0.00%) 
Nervous system disorders     
Dizziness   5/19 (26.32%)  5/17 (29.41%) 
Headache   3/19 (15.79%)  3/17 (17.65%) 
Psychiatric disorders     
Difficulty concentrating/memory impairment   0/19 (0.00%)  2/17 (11.76%) 
Reproductive system and breast disorders     
Spotting/abnormal menstrual bleeding   5/19 (26.32%)  2/17 (11.76%) 
Vaginal itching   1/19 (5.26%)  0/17 (0.00%) 
Hot flashes   0/19 (0.00%)  2/17 (11.76%) 
Cramps   0/19 (0.00%)  1/17 (5.88%) 
Breast tenderness   0/19 (0.00%)  3/17 (17.65%) 
Skin and subcutaneous tissue disorders     
Cracked nipple(s)   1/19 (5.26%)  1/17 (5.88%) 
Rash   1/19 (5.26%)  0/17 (0.00%) 
Hair loss   1/19 (5.26%)  0/17 (0.00%) 
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Dr. Crystal Schiller
Organization: University of North Carolina at Chapel Hill
Phone: 9199664810
Responsible Party: University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT01762943     History of Changes
Other Study ID Numbers: 12-1758
5R21MH101409 ( U.S. NIH Grant/Contract )
First Submitted: November 13, 2012
First Posted: January 8, 2013
Results First Submitted: September 15, 2017
Results First Posted: October 17, 2017
Last Update Posted: November 20, 2017