Cytokines, PUFA Tissue Concentrations and Treatment Selection in Antenatal MDD

NCT03101540 | Terminated Early Phase 1 FDA Drug

• 1 other identifier: 201102756
• Study Type: interventional
• Target: 27
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Major Depressive Disorder in Pregnancy

Keywords

Major Depressive Disorder,; omega-3 polyunsaturated fatty acid; PUFA; Pregnancy; eicosapentaenoic acid (EPA) supplementation; cytokine; docosahexaenoic acid (DHA)

Outcome Measures

Primary Outcomes (4)

• 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.

  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)

  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)

  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)

  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.

Study Arms (1)

Supplementation

EXPERIMENTAL

Subjects received Omega-3 PUFA supplementation

Drug: Omega-3 PUFA supplementation

Interventions

Omega-3 PUFA supplementation DRUG

Subjects received 2.2g of eicosapentaenoic acid (EPA) and 1.2g of docosahexaenoic acid (DHA) daily for the duration of the study.

Also known as: eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA)

Supplementation

Eligibility Criteria

• Age: 18 Years - 50 Years
• Gender Eligibility Details: This study is focused on pregnant women.
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• William Coryell: lead

Related Publications (4)

• 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.

  PMID: 12103448 BACKGROUND

• De 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.

  PMID: 14561523 BACKGROUND

• Peet 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.

  PMID: 9513745 BACKGROUND

• Rees 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.

  PMID: 19268372 BACKGROUND

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Eicosapentaenoic Acid; Docosahexaenoic Acids

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Fatty Acids, Omega-3; Dietary Fats, Unsaturated; Dietary Fats; Fats; Lipids; Eicosanoids; Fatty Acids, Unsaturated; Fatty Acids; Fish Oils; Oils

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: A single group model was used: pregnant women.

Study Record Dates

• First Submitted: March 29, 2017
• First Posted: April 5, 2017
• Study Start: August 1, 2011
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2014
• Last Updated: April 28, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will not share