We updated the design of this site on September 25th. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01762943
First Posted: January 8, 2013
Last Update Posted: October 17, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
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
  Purpose
Understanding the neural and biological mechanisms by which reproductive hormones influence mood is critically important for public health given that postpartum depression (PPD) is the leading cause of morbidity and mortality associated with childbirth and has negative effects on infants. Using a hormone-withdrawal challenge to precipitate mood symptoms will improve our ability to identify the biological mechanisms underlying both the triggering of and susceptibility to depressive disorders in women; and will permit the prediction of those at risk for PPD and other reproductive-related mood disorders.

Condition Intervention
Postpartum Depression Drug: Leuprolide Acetate Drug: Micronized estradiol Drug: Progesterone

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Neurophysiology of Postpartum Depression in an Experimental Model of Pregnancy and Parturition

Resource links provided by NLM:


Further study details as provided by University of North Carolina, Chapel Hill:

Primary Outcome Measures:
  • Blood-oxygen-level-dependent (BOLD) Response During Functional Magnetic Resonance Imaging (fMRI) z Statistic [ Time Frame: baseline and hormone withdrawal ]
    fMRI data collected during a Monetary Incentive Delay (MID) Task. For both tasks, the BOLD response was examined within the nucleus accumbens. The contrast of interest was win versus non-win outcomes in the MID Task. The z statistic reported 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. 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.


Secondary Outcome Measures:
  • Change in Inventory of Depression and Anxiety Symptoms (IDAS) Dysphoria Score [ Time Frame: Assessed at baseline and post-treatment ]
    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.


Enrollment: 36
Study Start Date: August 2013
Study Completion Date: October 13, 2016
Primary Completion Date: October 13, 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: Leuprolide Acetate
All subjects will receive one IM injection (3.75 mg) each month for four months.
Other Name: Lupron
Drug: 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.
Other Name: Estrace
Drug: 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.
Other Name: Micronized progesterone
Experimental: Women without any psychiatric history (Control)
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.
Drug: Leuprolide Acetate
All subjects will receive one IM injection (3.75 mg) each month for four months.
Other Name: Lupron
Drug: 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.
Other Name: Estrace
Drug: 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.
Other Name: Micronized progesterone

Detailed Description:
Affective disorders, such as PPD and other reproductive-related mood disorders, are common and constitute a significant burden for women, children, and society. However, little is known about the neurobiological mechanisms underlying depressive disorders in women. The long-term goal of this research is to 1) advance our understanding of the biological mechanisms underlying both the triggering of and susceptibility to depressive disorders in women; and 2) permit the prediction of those at risk for PPD. The objective of the current project is to examine whether those with a past episode of PPD (at "high risk" for recurrence) show differences in emotional arousal and reward processing domains relative to healthy control women (without a history of PPD) under baseline and hormone withdrawal-precipitated conditions. The central hypothesis is that reproductive hormone changes are associated with dysregulation of the neural circuits underlying emotional arousal and reward processing and consequent depressive symptoms in high-risk women. The rationale for the proposed study is that employing a scaled down model of puerperal hormonal events in high-risk women permits the identification of a group of individuals homogeneous for reproductive related affective dysfunction and, hence, the best opportunity for disentangling the specific changes in brain function due to reproductive hormones from those accompanying reproductive hormone-precipitated affective dysfunction. Moreover, identifying a neurophysiologic biomarker for hormone-related affective dysfunction provides a clear pathway for examining mechanisms of susceptibility to affective dysfunction across disorders. The investigators plan to accomplish the objectives of this application by pursuing the following specific aims: 1) to assess the effects of simulated postpartum reproductive hormone withdrawal, compared to baseline, on corticolimbic circuit activation in high-risk and control women; and 2) to examine the effects of reproductive hormone withdrawal, compared to baseline, on reward circuit activation in high-risk and control women. An additional exploratory aim is to identify a neural biomarker, characterized by corticolimbic and reward circuit dysfunction, that can be used to predict the onset of PPD. The proposed study involves experimentally manipulating reproductive hormones in euthymic women to create a scaled down version of the changes that occur at the puerperium. This endocrine manipulation paradigm will be used to examine the neurocircuitry underlying the regulation of affect and reward processing under baseline and hormone withdrawal-precipitated conditions among women who are expected to experience hormone-related affective dysregulation (n=15) and controls (n=15). In short, the investigators expect that relative to baseline, high-risk women will show greater dysregulation in neural circuits responsible for emotion processing and reward processing during hormone withdrawal than low-risk control women. The expected outcome of this research is the identification of neural circuits underlying both the susceptibility to and mediation of hormone-related affective dysfunction. Understanding these neurobiological mechanisms will subsequently improve the ability to identify those at risk for PPD, which may strengthen prevention efforts and ultimately prevent the deleterious effects of maternal depression on offspring.
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   22 Years to 50 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Group 1: Women with a history of PPD

  1. A history of a major depression episode that occurred within two months of childbirth (as determined by a SCID interview) and remitted at least one year prior to enrollment in the study;
  2. has been well for a minimum of one year;
  3. a regular menstrual cycle for at least three months;
  4. age 22-50;
  5. not pregnant, not lactating and in good medical health;
  6. medication free (not including birth control pills; participants may opt to temporarily discontinue birth control pills to participate);
  7. no history of puerperal suicide attempts or psychotic episodes requiring hospitalization.

Group 2: Healthy Controls

1) Controls will meet all inclusion criteria specified above except they must not have any past or present Axis I diagnosis or evidence of menstrually related mood disorders.

A structured clinical interview (SCID) will be administered to all women prior to study entry. Any woman with a current axis I psychiatric diagnosis will be excluded from participating in this protocol.

Exclusion Criteria:

Patients will not be permitted to enter this protocol if they have important clinical or laboratory abnormalities including any of the following:

  • current axis I psychiatric diagnosis
  • 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 required to agree to employ barrier contraceptive methods);
  • pregnancy-related medical conditions such as hyperemesis, pre-toxemia and toxemia, deep vein thrombosis (DVT) and bleeding diathesis;

Any woman with a first degree relative (immediate family) with either ovarian cancer, 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 perimenopause will be excluded from participation. Specifically, we will exclude any woman with an elevated plasma follicle stimulating hormone (FSH) level (> 14 IU/L) and with menstrual cycle variability of > 7 days different from their normal cycle length.

  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01762943


Locations
United States, North Carolina
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States, 27599-7175
Sponsors and Collaborators
University of North Carolina, Chapel Hill
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)
Investigators
Principal Investigator: Crystal E Schiller, Ph.D. University of North Carolina, Chapel Hill
Principal Investigator: David R Rubinow, M.D. University of North Carolina, Chapel Hill
  More Information

Additional Information:
Publications:
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: October 17, 2017
Last Verified: February 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depression, Postpartum
Behavioral Symptoms
Mood Disorders
Mental Disorders
Puerperal Disorders
Pregnancy Complications
Estradiol
Polyestradiol phosphate
Progesterone
Estradiol 3-benzoate
Estradiol 17 beta-cypionate
Estradiol valerate
Leuprolide
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Contraceptive Agents
Reproductive Control Agents
Contraceptive Agents, Female
Progestins
Fertility Agents, Female
Fertility Agents
Antineoplastic Agents, Hormonal
Antineoplastic Agents