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

NCT04156425 | Unknown

• 1 other identifier: 81930033
• Study Type: interventional
• Target: 180
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Major Depressive Disorder

Keywords

Major Depressive Disorder; neuroimmunology; Protein Kinase C

Outcome Measures

Primary Outcomes (1)

• remission of acute phase

  scored 7 or lower on the Hamilton's Depression Scale with 17 items

  12th week

Study Arms (3)

escitalopram + golimumab

EXPERIMENTAL

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

Drug: Escitalopram+golimumab

escitalopram + calcium tablet

EXPERIMENTAL

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

Dietary Supplement: Escitalopram+Calcium Tablet

escitalopram

ACTIVE COMPARATOR

Patients will be treated with escitalopram from the minimum dosage.

Drug: Escitalopram

Interventions

Escitalopram+golimumab 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.

Also known as: Lexapro+Simponi

escitalopram + golimumab

Escitalopram+Calcium Tablet 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.

Also known as: Lexapro+Caltrate

escitalopram + calcium tablet

Escitalopram DRUG

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

Also known as: Lexapro

escitalopram

Eligibility Criteria

• Age: 18 Years - 65 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shanghai Mental Health Center: lead

Related Publications (1)

• 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.

  PMID: 33912799 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Escitalopram

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Yiru Fang

  Shanghai Mental Health Center

  STUDY CHAIR

Central Study Contacts

Yiru Fang, MD. PhD.

CONTACT

021-64387250; yirufang@aliyun.com

Yiru Fang, MD. PhD.

CONTACT

(86) 18017311133; yirufang@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

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

Study Record Dates

• First Submitted: October 29, 2019
• First Posted: November 7, 2019
• Study Start: July 1, 2020
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: May 12, 2020

Record last verified: 2019-10