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Trial · Interventional

CompletedNot applicableResults postedRegistry data

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

NCTNCT01762943 (opens ClinicalTrials.gov in a new tab)Other id12-1758Other id5R21MH101409

Overview

Status
Completed
Phase
Not applicable
Enrollment
36 participants (actual)
Sponsor
University of North Carolina, Chapel Hill · Other
Design
Not randomized · Open label (no masking)
Countries
1 country

United States

Start
Aug 2013
Primary completion
13 Oct 2016
Completion
13 Oct 2016
First posted
8 Jan 2013 (estimated)
Last update posted
20 Nov 2017
Conditions
Postpartum Depression

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
20132014201520162017
  1. N/A

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

    NCT01762943

    Aug 2013 to 13 Oct 2016

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

  • Leuprolide AcetateDrug
  • Micronized estradiolDrug
  • ProgesteroneDrug

Arms2

  • 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.

  • 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.

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Blood-oxygen-level-dependent (BOLD) Response During Functional Magnetic Resonance Imaging (fMRI) z Statistic

    Time frame · baseline and hormone withdrawal

    Registry 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.

Secondary outcomes(1)
  1. Change in Inventory of Depression and Anxiety Symptoms (IDAS) Dysphoria Score

    Time frame · Assessed at baseline and post-treatment

    Registry 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.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeMean· baseline and hormone withdrawal

Blood-oxygen-level-dependent (BOLD) Response During Functional Magnetic Resonance Imaging (fMRI) z Statistic

GroupValue (z score)Spread
Women With a History of Postpartum Depression (PPD)2.31.13
Women Without Any Psychiatric History (Control)2.0.99
Secondary and other outcome results(1)
Secondary outcomeMean· Assessed at baseline and post-treatment

Change in Inventory of Depression and Anxiety Symptoms (IDAS) Dysphoria Score

GroupValue (units on a scale)Spread
Women With a History of Postpartum Depression (PPD)11.42.20
Women Without Any Psychiatric History (Control)12.73.08

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Women With Postpartum Depression (PPD)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.0 / 190 / 1912 / 19
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.0 / 170 / 1711 / 17

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Other registry references

References listed at the registry that are not in PepBank. They link to PubMed.

  • DerivedRudzinskas SA, Mazzu MA, Schiller CE, Meltzer-Brody S, Rubinow DR, Schmidt PJ, Goldman D. Divergent Transcriptomic Effects of Allopregnanolone in Postpartum Depression. Genes (Basel). 2023 Jun 8;14(6):1234. doi: 10.3390/genes14061234. PMID 37372414
  • DerivedRudzinskas SA, Goff AC, Mazzu MA, Schiller CE, Meltzer-Brody S, Rubinow DR, Schmidt PJ, Goldman D. Intrinsically dysregulated cellular stress signaling genes and gene networks in postpartum depression. Mol Psychiatry. 2023 Jul;28(7):3023-3032. doi: 10.1038/s41380-023-01985-5. Epub 2023 Feb 13. PMID 36782063

Eligibility

Who could join, as posted.

Sex
Female
Age
from 22 Years up to 50 Years
Healthy volunteers
Accepted
Inclusion and exclusion criteria, as posted
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.

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