Trial Outcomes & Findings for Neurophysiology of Postpartum Depression in an Experimental Model of Pregnancy and Parturition (NCT NCT01762943)

Last Updated: 2017-11-20

Results Overview

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.

Recruitment status

COMPLETED

Study phase

Target enrollment

36 participants

Primary outcome timeframe

baseline and hormone withdrawal

Results posted on

2017-11-20

Participant Flow

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).

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.

Participant milestones

Participant milestones
Measure	Women With Postpartum Depression (PPD) 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.	Women Without Any Psychiatric History (Control) 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 Study STARTED	19	17
Overall Study Hypogonadism	18	15
Overall Study Addback	16	15
Overall Study Withdrawal	15	15
Overall Study COMPLETED	15	15
Overall Study NOT COMPLETED	4	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Women With Postpartum Depression (PPD) 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.	Women Without Any Psychiatric History (Control) 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 Study Physician Decision	1	1
Overall Study Protocol Violation	1	0
Overall Study Withdrawal by Subject	2	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Women With Postpartum Depression (PPD) n=19 Participants 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.	Women Without Any Psychiatric History (Control) n=17 Participants 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 n=36 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	19 Participants n=5 Participants	17 Participants n=7 Participants	36 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	35.053 years STANDARD_DEVIATION 4.916 • n=5 Participants	36.294 years STANDARD_DEVIATION 4.224 • n=7 Participants	35.639 years STANDARD_DEVIATION 4.580 • n=5 Participants
Sex: Female, Male Female	19 Participants n=5 Participants	17 Participants n=7 Participants	36 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	16 Participants n=5 Participants	17 Participants n=7 Participants	33 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) White	14 Participants n=5 Participants	11 Participants n=7 Participants	25 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	19 Participants n=5 Participants	17 Participants n=7 Participants	36 Participants n=5 Participants

PRIMARY outcome

Timeframe: baseline and hormone withdrawal

Population: 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.

Outcome measures

Outcome measures
Measure	Women With a History of Postpartum Depression (PPD) n=14 Participants 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.	Women Without Any Psychiatric History (Control) n=15 Participants 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.
Blood-oxygen-level-dependent (BOLD) Response During Functional Magnetic Resonance Imaging (fMRI) z Statistic Left Nucleus Acc Baseline	2.3 z score Standard Deviation 1.13	2.0 z score Standard Deviation .99
Blood-oxygen-level-dependent (BOLD) Response During Functional Magnetic Resonance Imaging (fMRI) z Statistic Left Nucleus Acc Withdrawal	2.1 z score Standard Deviation 1.20	1.7 z score Standard Deviation .69
Blood-oxygen-level-dependent (BOLD) Response During Functional Magnetic Resonance Imaging (fMRI) z Statistic Right Nucleus Acc Baseline	2.2 z score Standard Deviation 1.12	2.0 z score Standard Deviation 1.09
Blood-oxygen-level-dependent (BOLD) Response During Functional Magnetic Resonance Imaging (fMRI) z Statistic Right Nucleus Acc Withdrawal	2.3 z score Standard Deviation 1.05	2.0 z score Standard Deviation .83

SECONDARY outcome

Timeframe: Assessed at baseline and post-treatment

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Women With a History of Postpartum Depression (PPD) n=15 Participants 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.	Women Without Any Psychiatric History (Control) n=15 Participants 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.
Change in Inventory of Depression and Anxiety Symptoms (IDAS) Dysphoria Score IDAS Dysphoria Baseline	11.4 units on a scale Standard Deviation 2.20	12.7 units on a scale Standard Deviation 3.08
Change in Inventory of Depression and Anxiety Symptoms (IDAS) Dysphoria Score IDAS Dysphoria Withdrawal	15.7 units on a scale Standard Deviation 8.29	11.1 units on a scale Standard Deviation 1.34

Adverse Events

Women With Postpartum Depression (PPD)

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Women Without Any Psychiatric History (Control)

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Dr. Crystal Schiller

University of North Carolina at Chapel Hill

Phone: 9199664810

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Women With Postpartum Depression (PPD) n=19 participants at risk 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.	Women Without Any Psychiatric History (Control) n=17 participants at risk 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.
General disorders Fatigue	31.6% 6/19 • Adverse event data were collected for every participant over the course of the 7-month-long protocol. Participants were asked about side effects at every study visit.	35.3% 6/17 • Adverse event data were collected for every participant over the course of the 7-month-long protocol. Participants were asked about side effects at every study visit.
Reproductive system and breast disorders Spotting/abnormal menstrual bleeding	26.3% 5/19 • Adverse event data were collected for every participant over the course of the 7-month-long protocol. Participants were asked about side effects at every study visit.	11.8% 2/17 • Adverse event data were collected for every participant over the course of the 7-month-long protocol. Participants were asked about side effects at every study visit.
Gastrointestinal disorders Nausea and/or vomiting	10.5% 2/19 • Adverse event data were collected for every participant over the course of the 7-month-long protocol. Participants were asked about side effects at every study visit.	5.9% 1/17 • Adverse event data were collected for every participant over the course of the 7-month-long protocol. Participants were asked about side effects at every study visit.
Nervous system disorders Dizziness	26.3% 5/19 • Adverse event data were collected for every participant over the course of the 7-month-long protocol. Participants were asked about side effects at every study visit.	29.4% 5/17 • Adverse event data were collected for every participant over the course of the 7-month-long protocol. Participants were asked about side effects at every study visit.
Skin and subcutaneous tissue disorders Cracked nipple(s)	5.3% 1/19 • Adverse event data were collected for every participant over the course of the 7-month-long protocol. Participants were asked about side effects at every study visit.	5.9% 1/17 • Adverse event data were collected for every participant over the course of the 7-month-long protocol. Participants were asked about side effects at every study visit.
Skin and subcutaneous tissue disorders Rash	5.3% 1/19 • Adverse event data were collected for every participant over the course of the 7-month-long protocol. Participants were asked about side effects at every study visit.	0.00% 0/17 • Adverse event data were collected for every participant over the course of the 7-month-long protocol. Participants were asked about side effects at every study visit.
Skin and subcutaneous tissue disorders Hair loss	5.3% 1/19 • Adverse event data were collected for every participant over the course of the 7-month-long protocol. Participants were asked about side effects at every study visit.	0.00% 0/17 • Adverse event data were collected for every participant over the course of the 7-month-long protocol. Participants were asked about side effects at every study visit.
Reproductive system and breast disorders Vaginal itching	5.3% 1/19 • Adverse event data were collected for every participant over the course of the 7-month-long protocol. Participants were asked about side effects at every study visit.	0.00% 0/17 • Adverse event data were collected for every participant over the course of the 7-month-long protocol. Participants were asked about side effects at every study visit.
Nervous system disorders Headache	15.8% 3/19 • Adverse event data were collected for every participant over the course of the 7-month-long protocol. Participants were asked about side effects at every study visit.	17.6% 3/17 • Adverse event data were collected for every participant over the course of the 7-month-long protocol. Participants were asked about side effects at every study visit.
Gastrointestinal disorders Diarrhea	5.3% 1/19 • Adverse event data were collected for every participant over the course of the 7-month-long protocol. Participants were asked about side effects at every study visit.	0.00% 0/17 • Adverse event data were collected for every participant over the course of the 7-month-long protocol. Participants were asked about side effects at every study visit.
Gastrointestinal disorders Constipation	0.00% 0/19 • Adverse event data were collected for every participant over the course of the 7-month-long protocol. Participants were asked about side effects at every study visit.	11.8% 2/17 • Adverse event data were collected for every participant over the course of the 7-month-long protocol. Participants were asked about side effects at every study visit.
Cardiac disorders Bradycardia or Arrhythmia	5.3% 1/19 • Adverse event data were collected for every participant over the course of the 7-month-long protocol. Participants were asked about side effects at every study visit.	5.9% 1/17 • Adverse event data were collected for every participant over the course of the 7-month-long protocol. Participants were asked about side effects at every study visit.
Musculoskeletal and connective tissue disorders Back pain	5.3% 1/19 • Adverse event data were collected for every participant over the course of the 7-month-long protocol. Participants were asked about side effects at every study visit.	0.00% 0/17 • Adverse event data were collected for every participant over the course of the 7-month-long protocol. Participants were asked about side effects at every study visit.
Cardiac disorders Chest pain	10.5% 2/19 • Adverse event data were collected for every participant over the course of the 7-month-long protocol. Participants were asked about side effects at every study visit.	0.00% 0/17 • Adverse event data were collected for every participant over the course of the 7-month-long protocol. Participants were asked about side effects at every study visit.
Psychiatric disorders Difficulty concentrating/memory impairment	0.00% 0/19 • Adverse event data were collected for every participant over the course of the 7-month-long protocol. Participants were asked about side effects at every study visit.	11.8% 2/17 • Adverse event data were collected for every participant over the course of the 7-month-long protocol. Participants were asked about side effects at every study visit.
Reproductive system and breast disorders Hot flashes	0.00% 0/19 • Adverse event data were collected for every participant over the course of the 7-month-long protocol. Participants were asked about side effects at every study visit.	11.8% 2/17 • Adverse event data were collected for every participant over the course of the 7-month-long protocol. Participants were asked about side effects at every study visit.
Gastrointestinal disorders Heartburn or reflux	0.00% 0/19 • Adverse event data were collected for every participant over the course of the 7-month-long protocol. Participants were asked about side effects at every study visit.	5.9% 1/17 • Adverse event data were collected for every participant over the course of the 7-month-long protocol. Participants were asked about side effects at every study visit.
Reproductive system and breast disorders Cramps	0.00% 0/19 • Adverse event data were collected for every participant over the course of the 7-month-long protocol. Participants were asked about side effects at every study visit.	5.9% 1/17 • Adverse event data were collected for every participant over the course of the 7-month-long protocol. Participants were asked about side effects at every study visit.
General disorders Weight gain	0.00% 0/19 • Adverse event data were collected for every participant over the course of the 7-month-long protocol. Participants were asked about side effects at every study visit.	5.9% 1/17 • Adverse event data were collected for every participant over the course of the 7-month-long protocol. Participants were asked about side effects at every study visit.
Reproductive system and breast disorders Breast tenderness	0.00% 0/19 • Adverse event data were collected for every participant over the course of the 7-month-long protocol. Participants were asked about side effects at every study visit.	17.6% 3/17 • Adverse event data were collected for every participant over the course of the 7-month-long protocol. Participants were asked about side effects at every study visit.