Major Depressive Disorder in PregnancyEarly Phase 1NCT03101527
Open Trial Determining Antidepressant Effects of Omega-3 Supplementation During Pregnancy
A Early Phase 1 study testing Omega-3 PUFA supplementation in people with Major Depressive Disorder in Pregnancy, run by William Coryell.
Trial summary
The purpose of this study is to determine if omega-3 polyunsaturated fatty acids as a monotherapy have antidepressant effects during pregnancy. It will also provide pilot data pertaining to relationships between apparent response to omega-3 monotherapy and both plasma cytokine and erythrocyte essential fatty acid… Read more about this study
- Who is it for?
- Ages 18 to 50 years, women only
- Conditions the study is for
- Major Depressive Disorder in Pregnancy
- What is being tested?
- Omega-3 PUFA supplementation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- No sites listed yet
- Study dates
- May 2011to Feb 2012
- Phase
- Early Phase 1
- 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 50 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Women with uncomplicated pregnancy within the 1st or 2nd trimester of pregnancy
- Score of 10 or greater on the nine item Patient Health Questionnaire (PHQ-9) for depression
Who cannot join
- antidepressant use in preceding month
- use in previous 4 weeks of psychotropic medications other than hypnotics or benzodiazepines in diazepam dose-equivalents greater than or equal to 2mg/day for insomnia
- Fish allergy
- initiation of regularly scheduled course of psychotherapy within previous 2 months
About this study
The purpose of this study is to determine if omega-3 polyunsaturated fatty acids as a monotherapy have antidepressant effects during pregnancy. It will also provide pilot data pertaining to relationships between apparent response to omega-3 monotherapy and both plasma cytokine and erythrocyte essential fatty acid concentrations.
Read the detailed description
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. Lingering 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. There is also now accumulating evidence that the SSRIs have short-, and perhaps longer-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 through fish intake is limited due to concerns over mercury levels. Because polyunsaturated fatty acids are dietary components essential for both fetal development and maternal health, and because their use as supplementation carries a minimal to non-existent side effect burden, women may be more likely to accept omega-3 supplementation over that of conventional antidepressants to manage depressive illness if provided sufficient evidence for effectiveness.
Data supporting the antidepressant potential of omega-3 PUFA supplementation derive first from numerous case-control studies that have associated depressive illness with lower tissue concentrations of omega-3 PUFAs and with higher ratios of omega-6 to omega-3. These findings prompted antidepressant trials of omega-3 supplementation as augmentation or as mono-therapy and many reports described significant benefits over placebo, including one that targeted pregnant women and yielded a large effect size. A number of other trials, however, failed to show clear antidepressant effects. Meta-analyses have highlighted these inconsistencies in results but have found no explanations for them in differing sample demographics, baseline depressive severity levels, PUFA dosing, or trial durations. Other sources of study outcome differences undoubtedly exist and a clear possibility is that the studies with positive results involved subjects more likely to truly benefit from omega-3 supplementation. The characteristics of such individuals are entirely unknown. Though valid predictors of antidepressant response to omega-3 PUFA supplementation would provide powerful tools for personalizing treatment no study has sought to identify them.
One feature that might characterize an individual likely to respond to omega-3 PUFA supplementation is, of course, the presence of relatively low tissue concentrations of omega-3 PUFAs and/or high ratios of omega-6 to omega-3 concentrations. The likelihood that omega-3 PUFA supplementation exerts antidepressant effects via modulation of the inflammatory cascade, and the extensive evidence that high levels of pro-inflammatory markers 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.
The identification of response predictors for a specific antidepressant strategy would not only have value for the selection of acute treatment for individuals with active depression but could also be used to choose preventative strategies for individuals who are not currently depressed but who are at high risk because of a recent history of a depressive episode. Prophylaxis against depressive illness in such individuals would have special importance during pregnancy. The adverse effects of depressive illness on both maternal and newborn well-being are widely appreciated but women who develop depressive disorders during pregnancy may, for a variety of reasons, fail to report symptoms to their health care provider or, if they do, treatment response may be delayed or even absent after one or more trials.
- Conditions
- Major Depressive Disorder in Pregnancy
- Being tested
- Omega-3 PUFA supplementation
- Keywords
- Major Depressive Disorder, omega-3 polyunsaturated fatty acid, PUFA, Pregnancy, eicosapentaenoic acid (EPA) supplementation
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Omega-3 PUFA supplementationDrug
Also called eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA)
Subjects received 2.2g of eicosapentaenoic acid (EPA) and 1.2g docosahexaenoic daily for the duration of the study
| Study group | Role | What they receive |
|---|---|---|
| Supplementation | Experimental | Subjects received Omega-3 PUFA supplementation Receives: Drug: Omega-3 PUFA supplementation |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Hamilton Rating Scale for Depression (HAM-D)
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.
Measured: Subjects were administered the HAM-D at Day 1 and every month thereafter until week 38 of their pregnancies.
Montgomery-Asberg Depression Scale (MADRS)
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.
Measured: Subjects were administered the MADRS on Day 1 and every month thereafter until week 38 of their pregnancies.
Edinburgh Postnatal Depression Scale (EPDS)
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.
Measured: Subjects were asked to complete the EPDS on Day 1 and every month thereafter until week 38 of their pregnancies
Beck Depression Scale (BDI)
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.
Measured: Subjects were asked to complete the BDI on Day 1 and every month thereafter through week 38 of their pregnancies
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Apr 2017
- Study startMay 2011
- Primary completionFeb 2012
- Study completionFeb 2012
Why it stopped: Insufficient recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Major Depressive Disorder in PregnancyStudies 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
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- A single group model was used: pregnant women.
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- William Coryell
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, William Coryell, University of Iowa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03101527
- Sponsor's protocol ID
- 201002781
- Status last verified
- Apr 2017
- First submitted
- 30 Mar 2017
- Last updated
- 28 Apr 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: The Investigator does not intend to share IPD
Publications
Hibbeln JR. Seafood consumption, the DHA content of mothers' milk and prevalence rates of postpartum depression: a cross-national, ecological analysis. J Affect Disord. 2002 May;69(1-3):15-29. doi: 10.1016/s0165-0327(01)00374-3.
PubMed 12103448De Vriese SR, Christophe AB, Maes M. Lowered serum n-3 polyunsaturated fatty acid (PUFA) levels predict the occurrence of postpartum depression: further evidence that lowered n-PUFAs are related to major depression. Life Sci. 2003 Nov 7;73(25):3181-7. doi: 10.1016/j.lfs.2003.02.001.
PubMed 14561523Peet M, Murphy B, Shay J, Horrobin D. Depletion of omega-3 fatty acid levels in red blood cell membranes of depressive patients. Biol Psychiatry. 1998 Mar 1;43(5):315-9. doi: 10.1016/s0006-3223(97)00206-0.
PubMed 9513745Rees AM, Austin MP, Owen C, Parker G. Omega-3 deficiency associated with perinatal depression: case control study. Psychiatry Res. 2009 Apr 30;166(2-3):254-9. doi: 10.1016/j.psychres.2007.12.011. Epub 2009 Mar 5.
PubMed 19268372
Study at a glance
From the registry record, last updated by the sponsor on 28 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open Trial Determining Antidepressant Effects of Omega-3 Supplementation During Pregnancy
- ClinicalTrials.gov ID
- NCT03101527
- Acronym / sponsor ID
- 201002781
- Conditions
- Major Depressive Disorder in Pregnancy
- Keywords
- Major Depressive Disorder, omega-3 polyunsaturated fatty acid, PUFA, Pregnancy, eicosapentaenoic acid (EPA) supplementation
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Insufficient recruitment
- Enrolment
- 3 participants (actual)
- Lead sponsor
- William CoryellUniversity, hospital or other
- Study start
- May 2011 (actual)
- Primary completion
- Feb 2012 (actual)
- Study completion
- Feb 2012 (actual)
- First posted
- 5 Apr 2017 (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 purpose of this study is to determine if omega-3 polyunsaturated fatty acids as a monotherapy have antidepressant effects during pregnancy. It will also provide pilot data pertaining to relationships between apparent response to omega-3 monotherapy and both plasma cytokine and erythrocyte essential fatty acid concentrations.
Detailed description
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. Lingering 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. There is also now accumulating evidence that the SSRIs have short-, and perhaps longer-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 through fish intake is limited due to concerns over mercury levels. Because polyunsaturated fatty acids are dietary components essential for both fetal development and maternal health, and because their use as supplementation carries a minimal to non-existent side effect burden, women may be more likely to accept omega-3 supplementation over that of conventional antidepressants to manage depressive illness if provided sufficient evidence for effectiveness.
Data supporting the antidepressant potential of omega-3 PUFA supplementation derive first from numerous case-control studies that have associated depressive illness with lower tissue concentrations of omega-3 PUFAs and with higher ratios of omega-6 to omega-3. These findings prompted antidepressant trials of omega-3 supplementation as augmentation or as mono-therapy and many reports described significant benefits over placebo, including one that targeted pregnant women and yielded a large effect size. A number of other trials, however, failed to show clear antidepressant effects. Meta-analyses have highlighted these inconsistencies in results but have found no explanations for them in differing sample demographics, baseline depressive severity levels, PUFA dosing, or trial durations. Other sources of study outcome differences undoubtedly exist and a clear possibility is that the studies with positive results involved subjects more likely to truly benefit from omega-3 supplementation. The characteristics of such individuals are entirely unknown. Though valid predictors of antidepressant response to omega-3 PUFA supplementation would provide powerful tools for personalizing treatment no study has sought to identify them.
One feature that might characterize an individual likely to respond to omega-3 PUFA supplementation is, of course, the presence of relatively low tissue concentrations of omega-3 PUFAs and/or high ratios of omega-6 to omega-3 concentrations. The likelihood that omega-3 PUFA supplementation exerts antidepressant effects via modulation of the inflammatory cascade, and the extensive evidence that high levels of pro-inflammatory markers 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.
The identification of response predictors for a specific antidepressant strategy would not only have value for the selection of acute treatment for individuals with active depression but could also be used to choose preventative strategies for individuals who are not currently depressed but who are at high risk because of a recent history of a depressive episode. Prophylaxis against depressive illness in such individuals would have special importance during pregnancy. The adverse effects of depressive illness on both maternal and newborn well-being are widely appreciated but women who develop depressive disorders during pregnancy may, for a variety of reasons, fail to report symptoms to their health care provider or, if they do, treatment response may be delayed or even absent after one or more trials.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- A single group model was used: pregnant women.
| Arm | Type | Receives |
|---|---|---|
| Supplementation | Experimental | Drug: Omega-3 PUFA supplementationSubjects received Omega-3 PUFA supplementation |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Women with uncomplicated pregnancy within the 1st or 2nd trimester of pregnancy
- Score of 10 or greater on the nine item Patient Health Questionnaire (PHQ-9) for depression
Key exclusion criteria (4 listed)
- antidepressant use in preceding month
- use in previous 4 weeks of psychotropic medications other than hypnotics or benzodiazepines in diazepam dose-equivalents greater than or equal to 2mg/day for insomnia
- Fish allergy
- initiation of regularly scheduled course of psychotherapy within previous 2 months
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 |
|---|---|---|
| Omega-3 PUFA supplementationAlso: eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA)Subjects received 2.2g of eicosapentaenoic acid (EPA) and 1.2g docosahexaenoic daily for the duration of the study | Drug | Supplementation |
Primary outcome
The 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.
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.
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.
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.
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
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.
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
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.
Results and safety
The study was stopped early (reason given: Insufficient recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Apr 2017.
- Background: PubMed 12103448Hibbeln JR. Seafood consumption, the DHA content of mothers' milk and prevalence rates of postpartum depression: a cross-national, ecological analysis. J Affect Disord. 2002 May;69(1-3):15-29. doi: 10.1016/s0165-0327(01)00374-3.
- Background: PubMed 14561523De Vriese SR, Christophe AB, Maes M. Lowered serum n-3 polyunsaturated fatty acid (PUFA) levels predict the occurrence of postpartum depression: further evidence that lowered n-PUFAs are related to major depression. Life Sci. 2003 Nov 7;73(25):3181-7. doi: 10.1016/j.lfs.2003.02.001.
- Background: PubMed 9513745Peet M, Murphy B, Shay J, Horrobin D. Depletion of omega-3 fatty acid levels in red blood cell membranes of depressive patients. Biol Psychiatry. 1998 Mar 1;43(5):315-9. doi: 10.1016/s0006-3223(97)00206-0.
- Background: PubMed 19268372Rees AM, Austin MP, Owen C, Parker G. Omega-3 deficiency associated with perinatal depression: case control study. Psychiatry Res. 2009 Apr 30;166(2-3):254-9. doi: 10.1016/j.psychres.2007.12.011. Epub 2009 Mar 5.
- Individual participant dataSharing planned: No. The Investigator does not intend to share IPD
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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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Omega-3 PUFA supplementation in people with Major Depressive Disorder in Pregnancy, run by William Coryell.
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 2 inclusion and 4 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: stopped early, as of the sponsor's last update on 28 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
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.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Insufficient recruitment). Results are not available in the source record.
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?
The 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.). 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 NCT03101527, which also lists 4 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 Apr 2017.