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

May 10, 2020 updated by: Shanghai Mental Health Center
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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

180

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
remission of acute phase
Time Frame: 12th week
scored 7 or lower on the Hamilton's Depression Scale with 17 items
12th week

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shanghai Mental Health Center

Investigators

  • Study Chair: Yiru Fang, Shanghai Mental Health Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

July 1, 2020

Primary Completion (Anticipated)

December 31, 2024

Study Completion (Anticipated)

December 31, 2024

Study Registration Dates

First Submitted

October 29, 2019

First Submitted That Met QC Criteria

November 5, 2019

First Posted (Actual)

November 7, 2019

Study Record Updates

Last Update Posted (Actual)

May 12, 2020

Last Update Submitted That Met QC Criteria

May 10, 2020

Last Verified

October 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 81930033

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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