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

Major Depressive Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04156425
• Other study ID #: 81930033
• Status: Not yet recruiting
• Phase: N/A
• Start date: July 1, 2020
• Est. completion date: December 31, 2024

Study information

• Verified date: October 2019
• Source: Shanghai Mental Health Center
• Contact: Yiru Fang, MD. PhD.
• Phone: 021-64387250
• Email: yirufang[@]aliyun.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 180
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

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.

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.

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Mental Health Center

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	remission of acute phase	scored 7 or lower on the Hamilton's Depression Scale with 17 items	12th week