Phospholipid Hypothesis of Depression: From Molecular Biology, Neuroimaging to Behaviour

Major Depressive Disorder Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02615405
• Other study ID #: NSC101-2628-B-039-001-MY3
• Status: Completed
• Phase: N/A
• First received: November 24, 2015
• Last updated: November 25, 2015
• Start date: August 2012
• Est. completion date: January 2015

Study information

• Verified date: November 2015
• Source: National Science Council, Taiwan
• Contact: n/a
• Is FDA regulated: No
• Health authority: Taiwan: Department of Health
• Study type: Interventional

Clinical Trial Summary

With the dissatisfaction of monoamine-based pharmacotherapy and the high comorbidity of physical illness in depression, the serotonin hypothesis seems to fail in approaching the etiology of depression. Based upon the evidence from epidemiological data, case-control studies of PUFAs compositions, and antidepressant effects in clinical trials, phospholipid polyunsaturated fatty acids (PUFAs) is enlightening a promising path to discover the unsolved of depression.

Description:

There are several important questions to answer regarding phospholipid polyunsaturated fatty acids (PUFAs) hypothesis of depression. Firstly, although case-control studies revealed that depressive patients had lower levels of omega-3 PUFAs, the abnormal findings in individual PUFA of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) or arachidonic acid (AA) are not consistent. Secondly, the deficits in n-3 PUFAs are related to their metabolic enzymes. However, the association study of polymorphisms of PUFA-metabolism related genes in depression is limited. Thirdly, the active component of antidepressant effect in n-3 PUFAs is still in debate. Fourthly, the molecular mechanisms of n-3 PUFAs' antidepressant effects have yet to be elucidated in human brain functional neuroimaging or in cellular models.

This 3-year proposal is divided into 2 clinical studies. In study 1, the investigators aim to test the clinical and biological effects of n-3 PUFAs (EPA: 3.5 g/d and DHA: 1.75 g/d versus placebo: high oleic oil) for depressive symptoms in a 12-week, double-blind, placebo-controlled trial of patients with drug-free MDD. In study 2, the investigators will measure the biological and neuroimaging markers to investigate the biological mechanisms of EPA (3.5 g/d) versus DHA (1.75 g/d) in 12-week, double-blind, randomized-controlled trial with patients with drug-free major depression disorder (MDD).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 240
• Est. completion date: January 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Diagnostic and Statistical Manual (DSM)-IV criteria for major depressive disorder

• Age being age 18-65.

• Capacity and willingness to give written informed consent.

• Free from antidepressants, mood stabilizers, and antipsychotics for more than 4 weeks.

Exclusion Criteria:

• Any major medical illnesses.

• A recent or past history of any Axis-I diagnoses besides major depressive disorder, including psychotic disorders; cognitively impaired mental disorders; impulse control disorders; substance use disorder or substance abuse (last 6 months prior to the studies); primary anxiety disorders, including post-traumatic stress disorder and panic disorder; and bipolar disorders; or Axis-II diagnoses, i.e. borderline and antisocial personality disorder.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

Dietary Supplement:
• EPA
A daily treatment of 5 identical capsules of EPA (3.5 g/d) for Studies 1 & 2.
• DHA
A daily treatment of 5 identical capsules of DHA (1.75 g/d) for Studies 1 & 2.
• Placebo
A daily treatment of 5 identical capsules of placebo (high oleic oil) in single or divided administration for Study 1.

Locations

Country	Name	City	State
Taiwan	China Medical University Hospital	Taichung

Sponsors (1)

Lead Sponsor	Collaborator
National Science Council, Taiwan

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes from Baseline Hamilton Depression Rating Scale (HDRS) at 12 weeks		Week 12	No
Primary	Remission rate		Week 12	No
Primary	Response rate		Week 12	No
Secondary	Changes in Beck Depression Inventory (BDI)		Week 12	No
Secondary	Changes in Neurotoxicity Rating Scale (NRS)		Week 12	Yes