The Role of PKC Activation in the Immune-inflammatory Mechanism of Major Depressive Depression

Sponsor

Shanghai Mental Health Center (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04156425

Collaborator

(none)

180

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Drug: Escitalopram+golimumab Dietary Supplement: Escitalopram+Calcium Tablet Drug: Escitalopram	N/A

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).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

180 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

group1：escitalopram + golimumab (N = 60), group2：escitalopram + calcium tablet (N = 60) group3：escitalopram +placebo (N = 60).group1：escitalopram + golimumab (N = 60), group2：escitalopram + calcium tablet (N = 60) group3：escitalopram +placebo (N = 60).

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

The Role of PKC Activation in the Immune-inflammatory Mechanism of Major Depressive Depression

Anticipated Study Start Date :

Jul 1, 2020

Anticipated Primary Completion Date :

Dec 31, 2024

Anticipated Study Completion Date :

Dec 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: escitalopram + golimumab Patients will be treated with escitalopram from the minimum dosage and golimumab according to direction for use.	Drug: Escitalopram+golimumab Escitalopram will be administered at 10-20 mg/d during the acute phase. Golimumab will be administered at the dose of 50mg every month during the acute phase. Other Names: Lexapro+Simponi
Experimental: escitalopram + calcium tablet Patients will be treated with escitalopram from the minimum dosage and calcium tablet according to direction for use.	Dietary Supplement: Escitalopram+Calcium Tablet Escitalopram will be administered at 10-20 mg/d during the acute phase. Calcium tablet will be administered at 2000mg/d during the acute phase. Other Names: Lexapro+Caltrate
Active Comparator: escitalopram Patients will be treated with escitalopram from the minimum dosage.	Drug: Escitalopram Escitalopram will be administered at 10-20 mg/d during the acute phase. Other Names: Lexapro

Arm

Intervention/Treatment

Experimental: escitalopram + golimumab

Patients will be treated with escitalopram from the minimum dosage and golimumab according to direction for use.

Drug: Escitalopram+golimumab

Escitalopram will be administered at 10-20 mg/d during the acute phase. Golimumab will be administered at the dose of 50mg every month during the acute phase.

Other Names:

Lexapro+Simponi

Experimental: escitalopram + calcium tablet

Patients will be treated with escitalopram from the minimum dosage and calcium tablet according to direction for use.

Dietary Supplement: Escitalopram+Calcium Tablet

Escitalopram will be administered at 10-20 mg/d during the acute phase. Calcium tablet will be administered at 2000mg/d during the acute phase.

Other Names:

Lexapro+Caltrate

Active Comparator: escitalopram

Patients will be treated with escitalopram from the minimum dosage.

Drug: Escitalopram

Escitalopram will be administered at 10-20 mg/d during the acute phase.

Other Names:

Lexapro

Outcome Measures

Primary Outcome Measures

remission of acute phase [12th week]
scored 7 or lower on the Hamilton's Depression Scale with 17 items

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

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

Exclusion Criteria:

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