Clinical trial NCT04156425: The Role of PKC Activation in the Immune-inflammatory Mechanism of Major Depressive Depression
Official title: The Role of PKC Activation in the Immune-inflammatory Mechanism of Major Depressive Depression
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Major Depressive Disorder
Keywords: Major Depressive Disorder
neuroimmunology
Protein Kinase C
Lead sponsor: Shanghai Mental Health Center
Sponsor class: OTHER
First posted: 2019-11-07
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: group1：escitalopram + golimumab (N = 60), group2：escitalopram + calcium tablet (N = 60) group3：escitalopram +placebo (N = 60).
Primary purpose: TREATMENT

Brief summary: Major Depressive disorder (MDD) is a heterogeneous mental illness. Treated with antidepressants that act on the neurotransmitter and/or their receptors just remitted only one third of patients with MDD, Thus, to improve the efficacy is a major unmet need for depression. Based on the scientific reports, inflammation plays a definite role in the development and treatment of depression, which may be an important way to understand and finally solve the problem. Our team found that there were significant changes in tumor necrosis factor (TNF)-α and other inflammatory factors in depressed patients, which caused neuronal apoptosis and depressive symptoms; PRKCB1(gene of protein kinase C-β) plays an anti-inflammatory role by regulating protein kinase C(PKC) activation in specific brain region, improving neuroplasticity and playing an antidepressant role. In this study, we assumes that the treatment-resistant depression patients maybe due to the immune inflammation and PKC activation inconsistency or unsynchronized, which couldn't reversible microglia polarization and neuronal apoptosis in specific brain regions, then, caused the significant changes at emotional and cognitive neural circuits, so as to exhibit such as emotional, cognitive symptoms of depression. Therefore, activating PKC and regulating immune/inflammatory process will be another way to improve the treatment outcome of depression. Take consideration, we focus on treatment-resistant depression patients, to validate the relationship between PKC activation and the immune inflammatory mechanism of depression, evaluate the antidepressant effect of golimumab or calcium tablet (a PKC activator) plus escitalopram, and initially proposes idividualized treatment strategies for MDD.

Detailed description: This is a randomized, double blind, placebo-controlled antidepressant augmentation trial. All participants are randomly divided into 3 groups treated orally with "escitalopram + golimumab" (N = 60), "escitalopram + calcium tablet" (N = 60) or "escitalopram +placebo" (N = 60).

Eligibility criteria: Inclusion Criteria:

1. Healthy men or women of matched age, gender and education with that of treatment-resistant depression (TRD) group;
2. A willingness to adhere to all prohibitions and restrictions necessary for the study;
3. Signed informed consent.

Exclusion Criteria:

1. Participant who have severe mental diseases, physical diseases, cerebrovascular disease, or a history of traumatic brain injury;
2. Participant who had a serious allergic reaction disease or those who have suffered from diseases of the immune system;
3. Participant who used anti-inflammatory drugs, or immunomodulatory drugs no more than 1 month prior randomization;
4. Pregnant or lactating female.

Primary outcomes:
measure: remission of acute phase
timeFrame: 12th week
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Shanghai Mental Health Center
name: Yiru Fang
role: STUDY_CHAIR
References:
citation: Guo X, Mao R, Cui L, Wang F, Zhou R, Wang Y, Huang J, Zhu Y, Yao Y, Zhao G, Li Z, Chen J, Wang J, Fang Y. PAID study design on the role of PKC activation in immune/inflammation-related depression: a randomised placebo-controlled trial protocol. Gen Psychiatr. 2021 Apr 5;34(2):e100440. doi: 10.1136/gpsych-2020-100440. eCollection 2021.