Clinical trial NCT02615405: Phospholipid Hypothesis of Depression: From Molecular Biology, Neuroimaging to Behaviour
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Major Depressive Disorder
Lead sponsor: National Science and Technology Council, Taiwan
Sponsor class: OTHER_GOV
First posted: 2015-11-26
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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).

Eligibility criteria: 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.

Primary outcomes:
measure: Changes from Baseline Hamilton Depression Rating Scale (HDRS) at 12 weeks
timeFrame: Week 12
measure: Remission rate
timeFrame: Week 12
measure: Response rate
timeFrame: Week 12
Secondary outcomes:
measure: Changes in Beck Depression Inventory (BDI)
timeFrame: Week 12
measure: Changes in Neurotoxicity Rating Scale (NRS)
timeFrame: Week 12
Other outcomes:
Locations:
city: Taichung
country: Taiwan
facility: China Medical University Hospital
Study officials:
affiliation: China Medical University Hospital
name: Kuan-Pin Su, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Su KP, Yang HT, Chang JP, Shih YH, Guu TW, Kumaran SS, Galecki P, Walczewska A, Pariante CM. Eicosapentaenoic and docosahexaenoic acids have different effects on peripheral phospholipase A2 gene expressions in acute depressed patients. Prog Neuropsychopharmacol Biol Psychiatry. 2018 Jan 3;80(Pt C):227-233. doi: 10.1016/j.pnpbp.2017.06.020. Epub 2017 Jun 23.