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

NCT ID: NCT04156425

Last Updated: 2020-05-12

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 180 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-01
• Study Completion Date: 2024-12-31

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).

Conditions

Major Depressive Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

escitalopram + golimumab

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

Group Type: EXPERIMENTAL

Escitalopram+golimumab

Intervention Type: DRUG

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.

escitalopram + calcium tablet

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

Group Type: EXPERIMENTAL

Escitalopram+Calcium Tablet

Intervention Type: DIETARY_SUPPLEMENT

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.

escitalopram

Patients will be treated with escitalopram from the minimum dosage.

Group Type: ACTIVE_COMPARATOR

Escitalopram

Intervention Type: DRUG

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

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: DIETARY_SUPPLEMENT

Escitalopram

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

Intervention Type: DRUG

Other Intervention Names

Lexapro+Simponi; Lexapro+Caltrate; Lexapro

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Shanghai Mental Health Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Yiru Fang

Role: STUDY_CHAIR

Shanghai Mental Health Center

Central Contacts

Yiru Fang, MD. PhD.

Role: CONTACT

yirufang@aliyun.com

021-64387250

Yiru Fang, MD. PhD.

Role: CONTACT

yirufang@gmail.com

(86) 18017311133

References

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.

Reference Type: DERIVED

PMID: 33912799 (View on PubMed)

Other Identifiers

81930033

Identifier Type: -

Identifier Source: org_study_id