Cytokines, PUFA Tissue Concentrations and Treatment Selection in Antenatal MDD

April 26, 2017 updated by: William Coryell
For a number of reasons women with major depressive disorder often discontinue conventional antidepressants when they become pregnant and prefer not to take them when depressive illness develops in the course of pregnancy. There is now considerable evidence that the administration of the omega-3 polyunsaturated fatty acid, eicosapentaenoic acid (EPA), as monotherapy has antidepressant effects. If it could be clearly established as effective such an approach would offer a valuable alternative for woman who are at risk for, or who develop, depressive disorder during pregnancy. Strongly positive placebo-controlled trials of EPA supplementation, though, co-exist with entirely negative ones. No clear reasons for these discrepancies have emerged but one possibility is that the samples studied have differed in the proportion of individuals likely to benefit from EPA supplementation. As there has been no effort to identify such individuals we propose to explore two groups of measures, both relevant to EPA's likely mechanisms of action, as potential tools for identifying individuals likely to benefit this treatment. Hypothesis: Among women who experience major depressive episodes during their first two trimesters of pregnancy, baseline measures of cytokine activity and erythrocyte PUFA concentrations will be associated, in an additive or interactive fashion, with subsequent improvement in depressive symptoms among women taking omega-3 PUFA supplementation.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

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Intervention / Treatment

Intervention / Treatment

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Detailed Description

This is a project to determine whether certain measures of nutritional status and immune functioning can be useful in the identification of women who would most benefit from omega-3 supplements as treatment for depression during pregnancy.

Pregnancy does not reduce the risk of recurrence among women who have previously experienced depressive illness and the advent of new episodes during pregnancy raises particular problems. Concerns over the possible teratogenicity of medications in general leave many women reluctant to continue preexisting antidepressant prophylaxis or to accept new trials of conventional antidepressant treatment and there is accumulating evidence that the SSRIs have short-term adverse effects on the newborn. The antidepressant effects of omega-3 polyunsaturated fatty acid (PUFA) supplementation may offer a particularly appropriate alternative to conventional therapy for depressive episodes that occur during pregnancy. The nutritional needs of the fetus increase the likelihood of omega-3 PUFA deficits in the mother but access to adequate omega-3 PUFAs but fish intake is limited due to concerns over mercury levels. Antidepressant trials of omega-3 supplementation that have described significant benefits over placebo include one that targeted pregnant women and yielded a large effect size. Other trials, however, have failed to show clear antidepressant effects and meta-analyses have yielded no explanations for these inconsistencies. A clear possibility is that the studies with positive results involved subjects who more likely to benefit from omega-3 supplementation but the characteristics of such individuals are entirely unknown. Numerous case-control studies have associated depressive illness with lower tissue concentration of omega-3 PUFAs and with higher ratios of omega-6 to omega-3. Such measures may well identify individuals likely show antidepressant effects from supplementation. The likelihood that omega-3 PUFAs exert antidepressant effects via modulation of the inflammatory cascade, and the extensive evidence that high levels of cytokines characterize individuals with depressive disorders, indicate that these measures too may help to select those most likely to benefit from treatment with omega-3 PUFAs. A group of 60 women who begin pregnancy in depressive episodes or who develop episodes in their first two trimesters but who choose not to take conventional antidepressant therapy would be used to test PUFA tissue concentration and inflammatory measures as predictors of response to omega-3 supplementation monotherapy. Aim #1: To determine, among women with first- or second-trimester major depressive episodes, relationships between subsequent response to omega-3 PUFA supplementation and baseline measures of PUFA erythrocyte concentrations and cytokine activity.

Hypothesis #1: Among women who experience major depressive episodes during their first two trimesters of pregnancy, baseline measures of cytokine activity and erythrocyte PUFA concentrations will be associated, in an additive or interactive fashion, with subsequent improvement in depressive symptoms among women taking omega-3 PUFA supplementation. Aim #1 will test whether measures of PUFA tissue concentrations and cytokine activity have potential value in treatment selection for women who experience depressive disorder during pregnancy. The strength with which measures correlate with symptom outcome will be used to select those for use in a definitive placebo-controlled trial that will target a sample enriched for those likely to respond to EPA supplementation.The measures that emerge most strongly as risk factors for new episodes would then be used to select subjects for participation in a placebo-controlled trial of EPA supplementation as prophylaxis against depressive disorder recurrence. The results would be integrated into the design of both acute treatment and prophylaxis trials.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
27

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Early Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 50 years (ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  1. women with uncomplicated pregnancies and within 24 weeks of their last menstrual period
  2. describe symptoms over the previous two weeks sufficient to meet DSM IV criteria for MDD as determined by the SCID
  3. have a 21-item HAM-D of 16 or more

Exclusion Criteria:

  1. antidepressant use in preceding month
  2. use in previous 2 wks of non-steroidal anti-inflammatory drugs (NSAIDS), antibiotics or glucocorticoids
  3. use in previous 2 wks of psychotropic medications other than hypnotics or benzodiazepines in diazepam dose-equivalents greater than 2mg/day for insomnia
  4. a previous diagnosis of an autoimmune disease, of hyperlipidemia, or of schizophrenia or schizoaffective disorder
  5. evidence of substance dependence in previous 6 months
  6. preoccupation with, or plans for, suicide
  7. a history of hypersensitivity to fish or fish oil supplements
  8. current use of anticoagulants
  9. any current medical condition associated with clinically significant decreases in coagulability, i.e. systemic lupus erythematosis, VonWillebrend's disease
  10. the initiation of regularly scheduled course of psychotherapy within the previous 2 months
  11. current use of category D or category X medications

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Supplementation
Subjects received Omega-3 PUFA supplementation
Drug: Omega-3 PUFA supplementation
Subjects received 2.2g of eicosapentaenoic acid (EPA) and 1.2g of docosahexaenoic acid (DHA) daily for the duration of the study.
Other Names:
  • eicosapentaenoic acid (EPA)
  • docosahexaenoic acid (DHA)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Hamilton Rating Scale for Depression (HAM-D)
Time Frame: Subjects were administered the HAM-D at Day 1 and every month thereafter until week 38 of their pregnancies. At 2 months postpartum it was again administered by phone.
The HAM-D is a multiple item semi-structured clinician administered questionnaire used to assess the range, type and severity of depressive symptoms observed in patients with MDD. The HAM-D24 consists of 24 symptoms, each of which is rated from 0 to 2 or 0 to 4, where 0 is none/absent. The HAMD-24 total score is calculated as the sum of the 24 individual symptom scores; the total score can range from 0 to 76. Higher HAMD-24 scores indicate more severe depression.
Subjects were administered the HAM-D at Day 1 and every month thereafter until week 38 of their pregnancies. At 2 months postpartum it was again administered by phone.
Montgomery-Asberg Depression Scale (MADRS)
Time Frame: Subjects were administered the MADRS on Day 1 and every month thereafter until week 38 of their pregnancies. At 2 months postpartum e ach subject was again administered the MADRS by phone.
The MADRS is a clinician administered semi-structured scaled designed to detect changes in depressive symptoms. The scale contains 10 items and ratings are graded from 0 to 6 , with 0 representing an absence of a symptom and 6 corresponding to the most severe degree of MDD symptomology.
Subjects were administered the MADRS on Day 1 and every month thereafter until week 38 of their pregnancies. At 2 months postpartum e ach subject was again administered the MADRS by phone.
Edinburgh Postnatal Depression Scale (EPDS)
Time Frame: Subjects were asked to complete the EPDS on Day 1 and every month thereafter until week 38 of their pregnancies and then again 2 months postpartum by phone.
The EPDS is a self-administered depression screen for postpartum women. The EPDS consists of 10 questions. Responses are scored 0,, 1, 2, or 3 according to increased severity of the symptom. Items marked with an * are reversed scored. A total score of 13 or more suggests follow-up intervention is warranted.
Subjects were asked to complete the EPDS on Day 1 and every month thereafter until week 38 of their pregnancies and then again 2 months postpartum by phone.
Beck Depression Scale (BDI)
Time Frame: Subjects were asked to complete the BDI on Day 1 and every month thereafter through week 38 of their pregnancies and then again 2 months postpartum by phone.
The BDI is a self-administered questionnaire developed to detect, assess, and monitor changes in depressive symptoms. It is composed of 21 items, each with 4 possible responses scored from 0 to 3 with 3 indicating a higher level of severity. For people who have been clinically diagnosed, scores from 0 to 9 represent minimal depressive symptoms, scores of 10 to 16 indicate mild depression, scores of 17 to 29 indicate moderate depression, and scores of 30 to 63 indicate severe depression.
Subjects were asked to complete the BDI on Day 1 and every month thereafter through week 38 of their pregnancies and then again 2 months postpartum by phone.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
William Coryell

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2011

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 1, 2014

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 1, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 29, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 30, 2017

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 5, 2017

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 28, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 26, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 201102756

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

The Investigator will not be sharing IPD

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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