Depression and SuicideNCT02566980
Biological Triggers of Depression in Pregnancy
An observational study of Depression and Suicide and Mood Disorders, run by Michigan State University at 3 sites in United States.
Trial summary
The goal of the study is to define and measure biological processes that contribute to the underlying pathophysiologic process of peri-partum depression to be used for identifying those at risk for developing it. Read more about this study
- Who is it for?
- Ages 18 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Depression and Suicide, Mood Disorders, Other Perinatal Conditions
- How many people
- 209 participants
- Where
- 3 sitesUnited States
- Study dates
- 23 Oct 2014to 28 Feb 2017
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Study population: Pregnant females age 18 and older, psychiatrically healthy or depressed; post-partum females experiencing perinatal depression with and without suicide ideation.
Who may be able to join
- Pre-partum cohort:
- All races and national origins of pregnant females.
- Age 18 and older.
- English speaking.
- Able to give informed consent.
- Able to comply with study procedures.
Show all 14Show fewer
- Post-partum cohort:
- All races and national origins of females who delivered a child vaginally or by caesarian section up to 6 months prior to enrollment.
- Age 18 and older.
- Edinburgh Perinatal Depression Rating Scale score of 10 and above and/or endorsed suicide ideation on the CSSRS.
- Depressive symptoms which began or worsened (if already present) during pregnancy or up to 4 weeks post-partum.
- Able to give informed consent.
- Able to comply with and complete study procedures.
- English speaking.
Who cannot join
- Pre-partum cohort:
- Non-pregnant females
- Patients with psychotic symptoms and/or severe cognitive impairment that interfere with their ability to give informed consent or to complete study assessments.
- Patients that cannot read and write in English as research measures used have only been validated in English speaking populations.
- Patients that have blood-borne chronic infections including hepatitis B, C, or HIV as established at routine pregnancy blood screens; they will be excluded as the laboratory facilities do not approve processing of their tissue for safety reasons.
- Patients who have any schizophrenia spectrum disorder or bipolar disorder type 1 (based on self report and SCID interview); these patients will be excluded as the neurobiology of these disorders are different from peripartum depression.
Show all 13Show fewer
- Patients who report ongoing substance abuse or dependence (in the past 3 months).
- Post-partum cohort:
- Patients with psychotic symptoms and/or severe cognitive impairment that interfere with their ability to give informed consent or to complete study assessments.
- Patients who cannot read and write in English as research measures used have only been validated in English speaking populations.
- Patients that have blood-borne chronic infections including hepatitis B, C, or HIV; as established at their routine pregnancy blood screens.
- Patients who have any schizophrenia spectrum disorder or bipolar type 1 (based on the self report and SCID interview).
- Patients who report ongoing substance abuse or dependence (past 3 months).
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Spectrum Health System
Grand Rapids, Michigan, 49503
Van Andel Research Institute
Grand Rapids, Michigan, 49503
Pine Rest Christian Mental Health Services
Grand Rapids, Michigan, 49548
About this study
Official title: The Role of Kynurenine Pathway Metabolites in Perinatal Depression and Suicidality
The goal of the study is to define and measure biological processes that contribute to the underlying pathophysiologic process of peri-partum depression to be used for identifying those at risk for developing it. This knowledge may also generate novel drug targets for peripartum depression that may be applicable to other types of depression.
Read the detailed description
This study analyses the role of inflammation and metabolites of inflammation in perinatal depression. Psychiatric assessments of depression and suicidality will be compared to blood levels of two metabolites of inflammation, quinolinic acid (QUIN) and picolinic acid (PIC), that might regulate nerve cell communication. The levels of these metabolites are regulated by kynurenine pathway enzymes.
Psychiatric symptoms, inflammatory cytokines and levels of the metabolites will be measured throughout pregnancy. Additionally, the investigators are gathering placentas at delivery and determining the degree of inflammation in the tissue in the investigators' laboratory. Inflammatory biomarkers, antibody titers, and key kynurenine pathway enzymes and metabolites from pre- and post partum women, placenta, and cord blood will be measured.
- Keywords
- depression, mood disorder, post-partum depression, suicidality, post-partum suicidality, perinatal depression, perinatal mood disorder, inflammation, kynurenine pathway, glutamate
- Medical subject headings
- Depression, Suicide, Mood Disorders, Depression, Postpartum, Suicidal Ideation, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Pre-partum | 130 pregnant women will be enrolled in first trimester. Healthy women or those with any degree of depressive symptoms are eligible. Blood samples and psychiatric assessments will take place once every trimester and once in the post-partum. At delivery placenta will be collected. Enrollment takes place at Spectrum Health Ob/gyn out-patient clinics in Grand Rapids, Michigan. | |
| Post-partum | 50-100 women experiencing perinatal depression with and without suicidality will be enrolled from a partial hospitalization program, the Mother and Baby unit as well as outpatient clinics at Pine Rest Christian Mental Health Services, Grand Rapids, Michigan. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in activity of the enzyme aminocarboxymuconate semialdehyde decarboxylase ACMSD in blood during pregnancy
Blood levels of quinolinic acid and picolinic acid (product of ACMSD) at three timepoints during pregnancy and one time-point after pregnancy
Measured: Up to pregnancy week 13 (1st sample), up to week 25 (second sample) and up to delivery (3rd sample) and post-partum (4th sample, within 6 months after delivery)
Activity of the enzyme aminocarboxymuconate semialdehyde decarboxylase ACMSD in placenta
Placenta levels of quinolinic acid and picolinic acid
Measured: At delivery
Increase in depressive symptoms
Assessment of depressive symptoms by means of the Edinburgh Postnatal Depression Scale
Measured: Up to pregnancy week 13 (1st assessment), up to week 25 (second assessment) and up to delivery (3rd assessment) and post-partum (4th assessment, within 6 months after delivery)
Suicidal symptoms
Assessment of suicidal symptoms by means of the Columbia Suicide Severity Rating Scale
Measured: Post-partum (within 6 months after delivery).
Secondary outcomes (2)
Change in blood inflammation
Analysis of the inflammatory cytokine IL-6 in blood
Measured: Up to pregnancy week 13 (1st sample), up to week 25 (second sample) and up to delivery (3rd sample) and post-partum (4th sample, within 6 months after delivery)
Placenta inflammation
Analysis of the expression of the inflammatory cytokine IL-6 in placental tissue
Measured: At delivery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2015 (estimated)
- Study start23 Oct 2014
- Primary completion28 Feb 2017
- Study completion28 Feb 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (23)Papers the sponsor has linked to this study.
- Other trials for Depression and SuicideStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 209 participants (actual)
Sponsor and investigators
- Lead sponsor
- Michigan State University
- Sponsor type
- University, hospital or other
- Collaborators
- Pine Rest Christian Mental Health Services, Van Andel Research Institute, Corewell Health West, National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Lena Brundin, Michigan State University
- Investigators
- Lena Brundin, MD, PhD, Principal investigator, Michigan State University, Van Andel Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02566980
- Sponsor's protocol ID
- 14-458M
- Other IDs
- 1R01MH104622-01
- Status last verified
- Jun 2018
- First submitted
- 25 Sep 2015
- Last updated
- 28 Jun 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
National Institute of Mental Health (NIMH), Statistics Use of Mental Health Services and Treatment among Adults. Availabe on-line at http://www.nimh.nih.gov/statistics/3USE_MT_ADULT.shtml.
World Health Organization (WHO). What Is Depression. Available on-line at http://www.who.int/mental_health/management/depression/definition/en/
First MB, Spitzer RL, Gibbon M, Williams JBW. Structured Clinical Interview for DSM-IV Axis I Disorders - Patient Edition (SCID-I/P, Version 2.0), Biometrics Research Department, New York State Psychiatric Institute, 1995.
Centers for Disease Control and Prevention (CDC). Prevalence of self-reported postpartum depressive symptoms--17 states, 2004-2005. MMWR Morb Mortal Wkly Rep. 2008 Apr 11;57(14):361-6.
PubMed 18401329Dietz PM, Williams SB, Callaghan WM, Bachman DJ, Whitlock EP, Hornbrook MC. Clinically identified maternal depression before, during, and after pregnancies ending in live births. Am J Psychiatry. 2007 Oct;164(10):1515-20. doi: 10.1176/appi.ajp.2007.06111893.
PubMed 17898342Marcus SM, Heringhausen JE. Depression in childbearing women: when depression complicates pregnancy. Prim Care. 2009 Mar;36(1):151-65, ix. doi: 10.1016/j.pop.2008.10.011.
PubMed 19231607Meltzer-Brody S, Boschloo L, Jones I, Sullivan PF, Penninx BW. The EPDS-Lifetime: assessment of lifetime prevalence and risk factors for perinatal depression in a large cohort of depressed women. Arch Womens Ment Health. 2013 Dec;16(6):465-73. doi: 10.1007/s00737-013-0372-9. Epub 2013 Aug 1.
PubMed 23904137Mian AI. Depression in pregnancy and the postpartum period: balancing adverse effects of untreated illness with treatment risks. J Psychiatr Pract. 2005 Nov;11(6):389-96. doi: 10.1097/00131746-200511000-00005.
PubMed 16304507Davalos DB, Yadon CA, Tregellas HC. Untreated prenatal maternal depression and the potential risks to offspring: a review. Arch Womens Ment Health. 2012 Feb;15(1):1-14. doi: 10.1007/s00737-011-0251-1. Epub 2012 Jan 4.
PubMed 22215285Anderson G, Maes M. Postpartum depression: psychoneuroimmunological underpinnings and treatment. Neuropsychiatr Dis Treat. 2013;9:277-87. doi: 10.2147/NDT.S25320. Epub 2013 Feb 21.
PubMed 23459664Groer MW, Morgan K. Immune, health and endocrine characteristics of depressed postpartum mothers. Psychoneuroendocrinology. 2007 Feb;32(2):133-9. doi: 10.1016/j.psyneuen.2006.11.007. Epub 2007 Jan 3.
PubMed 17207585Jolley SN, Elmore S, Barnard KE, Carr DB. Dysregulation of the hypothalamic-pituitary-adrenal axis in postpartum depression. Biol Res Nurs. 2007 Jan;8(3):210-22. doi: 10.1177/1099800406294598.
PubMed 17172320Koleva H, Stuart S, O'Hara MW, Bowman-Reif J. Risk factors for depressive symptoms during pregnancy. Arch Womens Ment Health. 2011 Apr;14(2):99-105. doi: 10.1007/s00737-010-0184-0. Epub 2010 Sep 25.
PubMed 20872153Meltzer-Brody S. Mental illness is prevalent among U.K. women in the perinatal period and is associated with socioeconomic deprivation. Evid Based Ment Health. 2013 May;16(2):57. doi: 10.1136/eb-2013-101226. Epub 2013 Mar 16. No abstract available.
PubMed 23503977Arck PC, Hecher K. Fetomaternal immune cross-talk and its consequences for maternal and offspring's health. Nat Med. 2013 May;19(5):548-56. doi: 10.1038/nm.3160. Epub 2013 May 7.
PubMed 23652115
Study at a glance
From the registry record, last updated by the sponsor on 28 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Kynurenine Pathway Metabolites in Perinatal Depression and Suicidality
- ClinicalTrials.gov ID
- NCT02566980
- Acronym / sponsor ID
- 14-458M
- Keywords
- depression, mood disorder, post-partum depression, suicidality, post-partum suicidality, perinatal depression, perinatal mood disorder, inflammation
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 209 participants (actual)
- Lead sponsor
- Michigan State UniversityUniversity, hospital or other
- Collaborators
- Pine Rest Christian Mental Health Services, Van Andel Research Institute, Corewell Health West, National Institute of Mental Health (NIMH)
- Study start
- 23 Oct 2014 (actual)
- Primary completion
- 28 Feb 2017 (actual)
- Study completion
- 28 Feb 2017 (actual)
- First posted
- 2 Oct 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of the study is to define and measure biological processes that contribute to the underlying pathophysiologic process of peri-partum depression to be used for identifying those at risk for developing it. This knowledge may also generate novel drug targets for peripartum depression that may be applicable to other types of depression.
Detailed description
This study analyses the role of inflammation and metabolites of inflammation in perinatal depression. Psychiatric assessments of depression and suicidality will be compared to blood levels of two metabolites of inflammation, quinolinic acid (QUIN) and picolinic acid (PIC), that might regulate nerve cell communication. The levels of these metabolites are regulated by kynurenine pathway enzymes.
Psychiatric symptoms, inflammatory cytokines and levels of the metabolites will be measured throughout pregnancy. Additionally, the investigators are gathering placentas at delivery and determining the degree of inflammation in the tissue in the investigators' laboratory. Inflammatory biomarkers, antibody titers, and key kynurenine pathway enzymes and metabolites from pre- and post partum women, placenta, and cord blood will be measured.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pre-partum | – | –130 pregnant women will be enrolled in first trimester. Healthy women or those with any degree of depressive symptoms are eligible. Blood samples and psychiatric assessments will take place once every trimester and once in the post-partum. At delivery placenta will be collected. Enrollment takes place at Spectrum Health Ob/gyn out-patient clinics in Grand Rapids, Michigan. |
| Post-partum | – | –50-100 women experiencing perinatal depression with and without suicidality will be enrolled from a partial hospitalization program, the Mother and Baby unit as well as outpatient clinics at Pine Rest Christian Mental Health Services, Grand Rapids, Michigan. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Pregnant females age 18 and older, psychiatrically healthy or depressed; post-partum females experiencing perinatal depression with and without suicide ideation.
Key inclusion criteria (14 listed)
- All races and national origins of pregnant females.
- Age 18 and older.
- English speaking.
- Able to give informed consent.
- Able to comply with study procedures.
Key exclusion criteria (13 listed)
- Non-pregnant females
- Patients with psychotic symptoms and/or severe cognitive impairment that interfere with their ability to give informed consent or to complete study assessments.
- Patients that cannot read and write in English as research measures used have only been validated in English speaking populations.
- Patients that have blood-borne chronic infections including hepatitis B, C, or HIV as established at routine pregnancy blood screens; they will be excluded as the laboratory facilities do not approve processing of their tissue for safety reasons.
- Patients who have any schizophrenia spectrum disorder or bipolar disorder type 1 (based on self report and SCID interview); these patients will be excluded as the neurobiology of these disorders are different from peripartum depression.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Change in activity of the enzyme aminocarboxymuconate semialdehyde decarboxylase ACMSD in blood during pregnancy
Time frame: Up to pregnancy week 13 (1st sample), up to week 25 (second sample) and up to delivery (3rd sample) and post-partum (4th sample, within 6 months after delivery)
Blood levels of quinolinic acid and picolinic acid (product of ACMSD) at three timepoints during pregnancy and one time-point after pregnancy
Activity of the enzyme aminocarboxymuconate semialdehyde decarboxylase ACMSD in placenta
Time frame: At delivery
Placenta levels of quinolinic acid and picolinic acid
Increase in depressive symptoms
Time frame: Up to pregnancy week 13 (1st assessment), up to week 25 (second assessment) and up to delivery (3rd assessment) and post-partum (4th assessment, within 6 months after delivery)
Assessment of depressive symptoms by means of the Edinburgh Postnatal Depression Scale
Suicidal symptoms
Time frame: Post-partum (within 6 months after delivery).
Assessment of suicidal symptoms by means of the Columbia Suicide Severity Rating Scale
2 secondary outcomes
Change in blood inflammation
Time frame: Up to pregnancy week 13 (1st sample), up to week 25 (second sample) and up to delivery (3rd sample) and post-partum (4th sample, within 6 months after delivery)
Placenta inflammation
Time frame: At delivery
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jun 2018.
- BackgroundNational Institute of Mental Health (NIMH), Statistics Use of Mental Health Services and Treatment among Adults. Availabe on-line at http://www.nimh.nih.gov/statistics/3USE_MT_ADULT.shtml.
- BackgroundWorld Health Organization (WHO). What Is Depression. Available on-line at http://www.who.int/mental_health/management/depression/definition/en/
- BackgroundFirst MB, Spitzer RL, Gibbon M, Williams JBW. Structured Clinical Interview for DSM-IV Axis I Disorders - Patient Edition (SCID-I/P, Version 2.0), Biometrics Research Department, New York State Psychiatric Institute, 1995.
- Background: PubMed 18401329Centers for Disease Control and Prevention (CDC). Prevalence of self-reported postpartum depressive symptoms--17 states, 2004-2005. MMWR Morb Mortal Wkly Rep. 2008 Apr 11;57(14):361-6.
- Background: PubMed 17898342Dietz PM, Williams SB, Callaghan WM, Bachman DJ, Whitlock EP, Hornbrook MC. Clinically identified maternal depression before, during, and after pregnancies ending in live births. Am J Psychiatry. 2007 Oct;164(10):1515-20. doi: 10.1176/appi.ajp.2007.06111893.
- Background: PubMed 19231607Marcus SM, Heringhausen JE. Depression in childbearing women: when depression complicates pregnancy. Prim Care. 2009 Mar;36(1):151-65, ix. doi: 10.1016/j.pop.2008.10.011.
- Background: PubMed 23904137Meltzer-Brody S, Boschloo L, Jones I, Sullivan PF, Penninx BW. The EPDS-Lifetime: assessment of lifetime prevalence and risk factors for perinatal depression in a large cohort of depressed women. Arch Womens Ment Health. 2013 Dec;16(6):465-73. doi: 10.1007/s00737-013-0372-9. Epub 2013 Aug 1.
- Background: PubMed 16304507Mian AI. Depression in pregnancy and the postpartum period: balancing adverse effects of untreated illness with treatment risks. J Psychiatr Pract. 2005 Nov;11(6):389-96. doi: 10.1097/00131746-200511000-00005.
- Background: PubMed 22215285Davalos DB, Yadon CA, Tregellas HC. Untreated prenatal maternal depression and the potential risks to offspring: a review. Arch Womens Ment Health. 2012 Feb;15(1):1-14. doi: 10.1007/s00737-011-0251-1. Epub 2012 Jan 4.
- Background: PubMed 23459664Anderson G, Maes M. Postpartum depression: psychoneuroimmunological underpinnings and treatment. Neuropsychiatr Dis Treat. 2013;9:277-87. doi: 10.2147/NDT.S25320. Epub 2013 Feb 21.
- Background: PubMed 17207585Groer MW, Morgan K. Immune, health and endocrine characteristics of depressed postpartum mothers. Psychoneuroendocrinology. 2007 Feb;32(2):133-9. doi: 10.1016/j.psyneuen.2006.11.007. Epub 2007 Jan 3.
- Background: PubMed 17172320Jolley SN, Elmore S, Barnard KE, Carr DB. Dysregulation of the hypothalamic-pituitary-adrenal axis in postpartum depression. Biol Res Nurs. 2007 Jan;8(3):210-22. doi: 10.1177/1099800406294598.
- Van Andel InstitutesLink provided by the sponsor.
- Pine Rest Christian Mental Health ServicesLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lena Brundin, MD, PhD principal investigator
Michigan State University, Van Andel Research Institute
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Depression and Suicide and Mood Disorders, run by Michigan State University at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in activity of the enzyme aminocarboxymuconate semialdehyde decarboxylase ACMSD in blood during pregnancy (time frame: Up to pregnancy week 13 (1st sample), up to week 25 (second sample) and up to delivery (3rd sample) and post-partum (4th sample, within 6 months after delivery)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02566980, which also lists 23 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jun 2018.