Clinical trial NCT03899194: Study on the Effect of PRKCB1 Modulating Inflammatory Factors and the Role for Developing Major Depressive Disorder
Official title: Study on the Effect of PRKCB1 Modulating Inflammatory Factors and the Role for Developing Major Depressive Disorder
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Major Depressive Disorder
Keywords: major depressive disorder
neuroimmunology
PRKCB1 gene
modulation
biomarker
Lead sponsor: Shanghai Mental Health Center
Sponsor class: OTHER
First posted: 2019-04-02
Enrollment: 350
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: group 1: escitalopram group 2: escitalopram + Omega-3 PUFAs
Primary purpose: TREATMENT

Brief summary: Depressive disorder is known as being accompanied with the activation of immune system which could lead to a series of changes including the neuron apoptosis, synapses transmission inhibition and emotional symptoms. The activation of protein kinase C (PKC) can reverse the immune/inflammatory process and restore the neuroplasticity and neurotransmitters transmission. Based on our finding that patients with major depressive disorder (MDD) showed a significantly lower gene expression of PRKCB1, while the PKC activation mediated by PRKCB1, we hypothesize that PRKCB1 contribute to the development of MDD and treatment response by its specific expression in brain, regulating ERBB, Chemokine signaling pathways and PKC activation during the neuroinflammatory process. In the present study, we aim to evaluate and verify the regulation effect of PRKCB1 on the neuroimmune and inflammatory mechanism in depressive disorder by a serious of studies focus on PRKCB1 gene expression modulating process and different downstream biomarkers which associated with PRKCB1 effect, combined with the specified treatment (plus omega-3 poly unsaturated fat acids). This study may provide scientific evidences for using neuroinflammatory biomarkers to diagnose MDD, as well as personalized treatment.

Detailed description: (1）To find out the differences of expression of mRNA, lncRNA, miRNA and proteins of PRKCB1 between patients with depressive disorder and healthy subjects.

(2) Patients with depressive disorders will be randomized into two groups that they will be treated with escitalopram or escitalopram plus Omega-3 PUFAs. To observe the effects of Omega-3 PUFAs on PRKCB1 and related neuroimmune/neuroinflammatory pathway which may improve understanding the relationship between neuroinflammatory regulation and depressive disorder treatment.

Eligibility criteria: Inclusion Criteria for patients:

1. Drug-naive or medication free for no less than 4 weeks;
2. 18-60 years old, Han nationality;
3. Junior high school diploma or above;
4. Meeting with the criteria of major depressive disorder in the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV-TR;
5. Scored 17 or higher on the Hamilton's Depression Scale with 17 items (HAMD-17) and scored 2 or higher for the 2nd item (depressive mood);
6. Written informed consent has been obtained.

Exclusion Criteria for patients:

1. Concurring psychotic disorders;
2. Woman who is pregnant or breast feeding or is planning to get pregnant;
3. Scores 3 or higher on item 3 (suicidal) of HAMD-17;
4. serious allergy or disease of immune system;
5. had anti-inflammatory drug or immunosuppressant in the past 1 month;
6. serious medical or surgical illness or history;
7. had MECT in the past 1 month.

Eligibility Criteria for healthy volunteers:

1. match the patient group in age, gender, education and handedness;
2. no history of psychiatric disorders or debilitating general medical disorders.

Primary outcomes:
measure: remission of acute phase
timeFrame: 12th week
measure: remission of consolidate and maintenance phase
timeFrame: 12th month
Secondary outcomes:
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Mental Health Center
state: Shanghai
Study officials:
affiliation: Shanghai Mental Health Center
name: Yiru Fang Fang, MD. PhD.
role: STUDY_CHAIR
References:
citation: Appleton KM, Voyias PD, Sallis HM, Dawson S, Ness AR, Churchill R, Perry R. Omega-3 fatty acids for depression in adults. Cochrane Database Syst Rev. 2021 Nov 24;11(11):CD004692. doi: 10.1002/14651858.CD004692.pub5.