Perinatal DepressionNCT04271072
CSF/Serum Biomarkers in Predicting PND/Persistent Pain After Cesarean
An observational study of Perinatal Depression and Chronic Pain, run by Duke University at 1 site in United States.
Trial summary
The aim is to investigate if inflammatory biomarkers in the blood and cerebrospinal fluid (CSF) are associated with the development of perinatal depression and/or persistent pain after cesarean delivery. This study will obtain CSF and blood samples in 70 parturients. Read more about this study
- Who is it for?
- Ages 18 to 40 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Perinatal Depression, Chronic Pain
- How many people
- 81 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Feb 2020to 28 Feb 2022
- 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 to 40 years
- Women only
- Healthy volunteers accepted
- Adult
Study population: Tertiary care hospital, specialist obstetric unit
Who may be able to join
- American Society of Anesthesiologists (ASA) class 2 and 3
- English speaking
- 18 years or older
- Singleton pregnancy
- Gestational age > 37 weeks
- Scheduled cesarean delivery under spinal or combined spinal epidural anesthesia
Who cannot join
- Intravenous drug or chronic opioid use
- Anti-depressant or anxiolytic drug use
- Allergy to standard of care drugs
- Cesarean delivery under general anesthesia or epidural anesthesia
- Pre-eclampsia needing magnesium sulfate
- Chronic PO/IV analgesic or glucocorticoids
- History of chronic pain syndromes
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center
Durham, North Carolina, 27710
About this study
Official title: The Role of Cerebrospinal Fluid and Serum Inflammatory Biomarkers in Predicting Perinatal Depression and Persistent Pain After Cesarean Delivery
The aim is to investigate if inflammatory biomarkers in the blood and cerebrospinal fluid (CSF) are associated with the development of perinatal depression and/or persistent pain after cesarean delivery.
This study will obtain CSF and blood samples in 70 parturients. All parturients will be assessed for perinatal depression and persistent pain, and the presence/absence of these outcomes will be correlated to changes in the inflammatory biomarkers within the samples collected. If present, consistent changes in biomarkers correlating with perinatal depression or persistent pain may be utilised as a predictive tool and facilitate early treatment for these conditions.
Read the detailed description
Persistent pain and perinatal depression (PND) contribute significantly to maternal morbidity and mortality after cesarean delivery. Neuroinflammation has been associated with both persistent pain and perinatal depression, and may therefore be a common etiological process, however, little is known of the association between neuroinflammation and persistent pain or PND in parturients undergoing cesarean delivery.
Aim 1: To compare neuroinflammatory cytokine profiles (in CSF and plasma samples within 48 hours after surgery) between the cohort of parturients that develop the composite outcome of persistent pain or PND (defined below), versus the cohort of parturients that did not develop this outcome.
Aim 2. To determine the correlation between the neuroinflammatory cytokine profiles of CSF and plasma.
Exploratory aim: To determine the change in plasma inflammatory cytokine profile from the antenatal to the postnatal period, and correlate this change with preoperative quantitative sensory tests, acute postsurgical pain severity, and development of persistent pain and/or PND. To examine proteomics in CSF and correlate with persistent pain and/or PND.
This is a prospective cohort study of 70 adult parturients undergoing elective cesarean delivery at Duke University Hospital. After obtaining informed consent, baseline demographic data, the Edinburgh Postnatal Depression Scale (EPDS), mechanical temporal summation (MTS), and pain-pressure threshold (PPT) tests will be administered. During IV cannulation, 10ml of blood will be collected, and up to 10ml CSF will be collected during spinal anesthesia. After cesarean delivery, pain scores, analgesia requirements, and data on adverse events will be collected. Additional 10ml of blood will be collected within 48 hours post-surgery during inpatient hospital stay. During the routine 6-week postnatal follow up, EPDS scores will be recorded, and at 3-months, EPDS and persistent pain assessment will be conducted over the phone.
Based on a composite endpoint of persistent pain (pain at 3 months after surgery) or PND (EPDS of 10 or greater, during pregnancy or within 3 months after delivery), parturients will be stratified into "study" or "control" cohorts. Using a validated multiplex quantitative proteomic approach, candidate biomarkers will be quantified and correlated against the composite outcome using two-sided Mann-Whitney U test. Correlation between CSF and plasma cytokines will be assessed using spearman correlation. The exploratory aim will be analyzed with generalized linear models.
- Conditions
- Perinatal Depression, Chronic Pain
- Being tested
- No intervention
- Keywords
- Neuroinflammation, Biomarker, Cesarean delivery, Cytokines, Cerebrospinal fluid
- Medical subject headings
- Chronic Pain, Neuroinflammatory Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
No interventionOther
No intervention
| Study group | Role | What they receive |
|---|---|---|
| Study | Parturients that underwent cesarean delivery and is POSITIVE for the composite outcome of either:
* perinatal depression (Edinburgh postnatal depression scale >=10 during pregnancy or within 3 months after delivery), and/or
* persistent pain (pain score >=3 at pelvic or lower abdominal areas at 3 months after delivery) Receives: Other: No intervention | |
| Control | Parturients that underwent cesarean delivery and is NEGATIVE for the composite outcome of both:
* perinatal depression (Edinburgh postnatal depression scale >=10 during pregnancy or within 3 months after delivery), AND
* persistent pain (pain score >=3 at pelvic or lower abdominal areas at 3 months after delivery) Receives: Other: No intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Perinatal depression
Edinburgh postnatal depression scale >=10 (minimum 0, maximum 30, increasing score indicates higher likelihood of depression)
Measured: Up to 3 months after delivery
Persistent pain: Pain score
Pain score >=3 at pelvic or lower abdominal areas (minimum 0, maximum 10, higher score indicates greater pain)
Measured: Up to 3 months after delivery
Inflammatory cytokines/biomarkers
Biomarkers from CSF and plasma samples will be quantified using Meso Scale Discovery multiplex kit (K15210D), for:
CRP, Eotaxin, Eotaxin-3, FGF (basic), ICAM-1, IFN-γ, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12/IL-23p40, IL-13, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, PlGF, SAA, TARC, Tie-2, TNF-α, TNF-β, VCAM-1, VEGF-A, VEGF-C, VEGF-D, VEGFR-1/Flt-1.
The levels of these biomarkers will be compared between the group with depression/persistent pain, versus the group without depression/persistent pain.
Measured: Up to 24 hours after surgery
Secondary outcomes (1)
CSF compared to plasma inflammatory cytokines/biomarkers
Biomarkers will be quantified using Meso Scale Discovery multiplex kit (K15210D), for:
CRP, Eotaxin, Eotaxin-3, FGF (basic), ICAM-1, IFN-γ, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12/IL-23p40, IL-13, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, PlGF, SAA, TARC, Tie-2, TNF-α, TNF-β, VCAM-1, VEGF-A, VEGF-C, VEGF-D, VEGFR-1/Flt-1
The CSF and plasma levels of these biomarkers will be compared within each group (group with depression/persistent pain, versus group without depression/persistent pain)
Measured: Preoperative samples
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2020
- Study start1 Feb 2020
- Primary completion28 Feb 2022
- Study completion28 Feb 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Perinatal DepressionStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe sponsor's other registered studies.
- 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
- 81 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mary Yurashevich, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04271072
- Sponsor's protocol ID
- Pro00104111
- Status last verified
- Dec 2023
- First submitted
- 7 Feb 2020
- Last updated
- 20 Dec 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Kohler CA, Freitas TH, Maes M, de Andrade NQ, Liu CS, Fernandes BS, Stubbs B, Solmi M, Veronese N, Herrmann N, Raison CL, Miller BJ, Lanctot KL, Carvalho AF. Peripheral cytokine and chemokine alterations in depression: a meta-analysis of 82 studies. Acta Psychiatr Scand. 2017 May;135(5):373-387. doi: 10.1111/acps.12698. Epub 2017 Jan 25.
PubMed 28122130Miller ES, Sakowicz A, Roy A, Yang A, Sullivan JT, Grobman WA, Wisner KL. Plasma and cerebrospinal fluid inflammatory cytokines in perinatal depression. Am J Obstet Gynecol. 2019 Mar;220(3):271.e1-271.e10. doi: 10.1016/j.ajog.2018.12.015. Epub 2018 Dec 14.
PubMed 30557551Osborne LM, Monk C. Perinatal depression--the fourth inflammatory morbidity of pregnancy?: Theory and literature review. Psychoneuroendocrinology. 2013 Oct;38(10):1929-52. doi: 10.1016/j.psyneuen.2013.03.019. Epub 2013 Apr 20.
PubMed 23608136Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, Lanctot KL. A meta-analysis of cytokines in major depression. Biol Psychiatry. 2010 Mar 1;67(5):446-57. doi: 10.1016/j.biopsych.2009.09.033. Epub 2009 Dec 16.
PubMed 20015486Ji RR, Nackley A, Huh Y, Terrando N, Maixner W. Neuroinflammation and Central Sensitization in Chronic and Widespread Pain. Anesthesiology. 2018 Aug;129(2):343-366. doi: 10.1097/ALN.0000000000002130.
PubMed 29462012Yurashevich M, Cooter Wright M, Sims SC, Tan HS, Berger M, Ji RR, Habib AS. Inflammatory changes in the plasma and cerebrospinal fluid of patients with persistent pain and postpartum depression after elective Cesarean delivery: an exploratory prospective cohort study. Can J Anaesth. 2023 Dec;70(12):1917-1927. doi: 10.1007/s12630-023-02603-2. Epub 2023 Nov 6.
PubMed 37932648
Study at a glance
From the registry record, last updated by the sponsor on 20 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Cerebrospinal Fluid and Serum Inflammatory Biomarkers in Predicting Perinatal Depression and Persistent Pain After Cesarean Delivery
- ClinicalTrials.gov ID
- NCT04271072
- Acronym / sponsor ID
- Pro00104111
- Conditions
- Perinatal Depression, Chronic Pain
- Keywords
- Neuroinflammation, Biomarker, Cesarean delivery, Cytokines, Cerebrospinal fluid
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 81 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Study start
- 1 Feb 2020 (actual)
- Primary completion
- 28 Feb 2022 (actual)
- Study completion
- 28 Feb 2022 (actual)
- First posted
- 17 Feb 2020 (actual)
- 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 aim is to investigate if inflammatory biomarkers in the blood and cerebrospinal fluid (CSF) are associated with the development of perinatal depression and/or persistent pain after cesarean delivery.
This study will obtain CSF and blood samples in 70 parturients. All parturients will be assessed for perinatal depression and persistent pain, and the presence/absence of these outcomes will be correlated to changes in the inflammatory biomarkers within the samples collected. If present, consistent changes in biomarkers correlating with perinatal depression or persistent pain may be utilised as a predictive tool and facilitate early treatment for these conditions.
Detailed description
Persistent pain and perinatal depression (PND) contribute significantly to maternal morbidity and mortality after cesarean delivery. Neuroinflammation has been associated with both persistent pain and perinatal depression, and may therefore be a common etiological process, however, little is known of the association between neuroinflammation and persistent pain or PND in parturients undergoing cesarean delivery.
Aim 1: To compare neuroinflammatory cytokine profiles (in CSF and plasma samples within 48 hours after surgery) between the cohort of parturients that develop the composite outcome of persistent pain or PND (defined below), versus the cohort of parturients that did not develop this outcome.
Aim 2. To determine the correlation between the neuroinflammatory cytokine profiles of CSF and plasma.
Exploratory aim: To determine the change in plasma inflammatory cytokine profile from the antenatal to the postnatal period, and correlate this change with preoperative quantitative sensory tests, acute postsurgical pain severity, and development of persistent pain and/or PND. To examine proteomics in CSF and correlate with persistent pain and/or PND.
This is a prospective cohort study of 70 adult parturients undergoing elective cesarean delivery at Duke University Hospital. After obtaining informed consent, baseline demographic data, the Edinburgh Postnatal Depression Scale (EPDS), mechanical temporal summation (MTS), and pain-pressure threshold (PPT) tests will be administered. During IV cannulation, 10ml of blood will be collected, and up to 10ml CSF will be collected during spinal anesthesia. After cesarean delivery, pain scores, analgesia requirements, and data on adverse events will be collected. Additional 10ml of blood will be collected within 48 hours post-surgery during inpatient hospital stay. During the routine 6-week postnatal follow up, EPDS scores will be recorded, and at 3-months, EPDS and persistent pain assessment will be conducted over the phone.
Based on a composite endpoint of persistent pain (pain at 3 months after surgery) or PND (EPDS of 10 or greater, during pregnancy or within 3 months after delivery), parturients will be stratified into "study" or "control" cohorts. Using a validated multiplex quantitative proteomic approach, candidate biomarkers will be quantified and correlated against the composite outcome using two-sided Mann-Whitney U test. Correlation between CSF and plasma cytokines will be assessed using spearman correlation. The exploratory aim will be analyzed with generalized linear models.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Study | – | Other: No interventionParturients that underwent cesarean delivery and is POSITIVE for the composite outcome of either: * perinatal depression (Edinburgh postnatal depression scale >=10 during pregnancy or within 3 months after delivery), and/or * persistent pain (pain score >=3 at pelvic or lower abdominal areas at 3 months after delivery) |
| Control | – | Other: No interventionParturients that underwent cesarean delivery and is NEGATIVE for the composite outcome of both: * perinatal depression (Edinburgh postnatal depression scale >=10 during pregnancy or within 3 months after delivery), AND * persistent pain (pain score >=3 at pelvic or lower abdominal areas at 3 months after delivery) |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- Tertiary care hospital, specialist obstetric unit
Key inclusion criteria (6 listed)
- American Society of Anesthesiologists (ASA) class 2 and 3
- English speaking
- 18 years or older
- Singleton pregnancy
- Gestational age > 37 weeks
Key exclusion criteria (7 listed)
- Intravenous drug or chronic opioid use
- Anti-depressant or anxiolytic drug use
- Allergy to standard of care drugs
- Cesarean delivery under general anesthesia or epidural anesthesia
- Pre-eclampsia needing magnesium sulfate
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| No interventionNo intervention | Other | Control, Study |
Primary outcome
Perinatal depression
Time frame: Up to 3 months after delivery
Edinburgh postnatal depression scale >=10 (minimum 0, maximum 30, increasing score indicates higher likelihood of depression)
Persistent pain: Pain score
Time frame: Up to 3 months after delivery
Pain score >=3 at pelvic or lower abdominal areas (minimum 0, maximum 10, higher score indicates greater pain)
Inflammatory cytokines/biomarkers
Time frame: Up to 24 hours after surgery
Biomarkers from CSF and plasma samples will be quantified using Meso Scale Discovery multiplex kit (K15210D), for: CRP, Eotaxin, Eotaxin-3, FGF (basic), ICAM-1, IFN-γ, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12/IL-23p40, IL-13, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, PlGF, SAA, TARC, Tie-2, TNF-α, TNF-β, VCAM-1, VEGF-A, VEGF-C, VEGF-D, VEGFR-1/Flt-1. The levels of these biomarkers will be compared between the group with depression/persistent pain, versus the group without depression/persistent pain.
1 secondary outcome
CSF compared to plasma inflammatory cytokines/biomarkers
Time frame: Preoperative samples
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 20 Dec 2023.
- Background: PubMed 28122130Kohler CA, Freitas TH, Maes M, de Andrade NQ, Liu CS, Fernandes BS, Stubbs B, Solmi M, Veronese N, Herrmann N, Raison CL, Miller BJ, Lanctot KL, Carvalho AF. Peripheral cytokine and chemokine alterations in depression: a meta-analysis of 82 studies. Acta Psychiatr Scand. 2017 May;135(5):373-387. doi: 10.1111/acps.12698. Epub 2017 Jan 25.
- Background: PubMed 30557551Miller ES, Sakowicz A, Roy A, Yang A, Sullivan JT, Grobman WA, Wisner KL. Plasma and cerebrospinal fluid inflammatory cytokines in perinatal depression. Am J Obstet Gynecol. 2019 Mar;220(3):271.e1-271.e10. doi: 10.1016/j.ajog.2018.12.015. Epub 2018 Dec 14.
- Background: PubMed 23608136Osborne LM, Monk C. Perinatal depression--the fourth inflammatory morbidity of pregnancy?: Theory and literature review. Psychoneuroendocrinology. 2013 Oct;38(10):1929-52. doi: 10.1016/j.psyneuen.2013.03.019. Epub 2013 Apr 20.
- Background: PubMed 20015486Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, Lanctot KL. A meta-analysis of cytokines in major depression. Biol Psychiatry. 2010 Mar 1;67(5):446-57. doi: 10.1016/j.biopsych.2009.09.033. Epub 2009 Dec 16.
- Background: PubMed 29462012Ji RR, Nackley A, Huh Y, Terrando N, Maixner W. Neuroinflammation and Central Sensitization in Chronic and Widespread Pain. Anesthesiology. 2018 Aug;129(2):343-366. doi: 10.1097/ALN.0000000000002130.
- Derived from this study: PubMed 37932648Yurashevich M, Cooter Wright M, Sims SC, Tan HS, Berger M, Ji RR, Habib AS. Inflammatory changes in the plasma and cerebrospinal fluid of patients with persistent pain and postpartum depression after elective Cesarean delivery: an exploratory prospective cohort study. Can J Anaesth. 2023 Dec;70(12):1917-1927. doi: 10.1007/s12630-023-02603-2. Epub 2023 Nov 6.
- 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.
Mary Yurashevich principal investigator
Duke University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Perinatal Depression and Chronic Pain, run by Duke University at 1 site 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 6 inclusion and 7 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 20 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Perinatal depression (time frame: Up to 3 months after delivery). The study lists 3 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 NCT04271072, which also lists 6 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 20 Dec 2023; AzTrials last refreshed its copy on 6 Nov 2026.