PKC as Serum Biomarkers for Depression

Inflammation that is mediated by microglia activation plays an important role in the pathogenesis of depression. Microglia activation can lead to an increase in the levels of proinflammatory cytokines, including TNF-α, which leads to neuronal apoptosis in the specific neural circuits of some brain regions, abnormal cognition, and treatment-resistant depression (TRD). Protein kinase C (PKC) is a key regulator of the microglia activation process. The investigators assume that the abnormality in PKC might be the serum biomarkers of depression.

Study Overview

• Status: Unknown
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: SSRI + golimumab; Other: SSRI + placebo

Detailed Description

PKC activation might reduce M1 microglia activation and the release of proinflammatory cytokines such as TNF-α, finally alleviating depressive symptoms in TRD.

Primary objective: This study was designed to address the role of PKC-mediated microglial activation in the clinical outcome of first episode depression.

Secondary objective: To illustrate the impact of PKC-mediated microglial activation on impaired cognition, social function and neuronal plasticity.

The investigators adopted randomized design to test placebo-controlled antidepressant augmentation. Patients were randomized (1:1) into one of the following 2groups: "SSRI +golimumab"," or "SSRI +placebo". The total study duration is 12 weeks

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosed with major depressive disorder (MDD) according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5);

  • Insufficient response (response rate <50%) to two antidepressants with different mechanisms when given for at least 6 weeks at an adequate dose (e.g., clomipramine ≥150 mg/d, fluoxetine≥20 mg/d) during the current episode;

    • A 17-item Hamilton Depression Rating Scale (HAMD-17) score ≥ 17 no more than 7 days prior to randomization. Cognitive factors (including a sense of guilt, suicidal thoughts, agitation, depersonalization, the disintegration of reality, paranoid symptoms, and obsessive and compulsive symptoms) score ≥6; ④ Between 18 and 65 years of age;

      ⑤ Education: finished junior middle school;

      ⑥ Ethnicity: Han Chinese;

      • Adequate audio and visual levels to complete the necessary checks; ⑧ Compliance with treatment in the clinical trial.

Exclusion Criteria:

• Severe liver and kidney diseases, active endocrine diseases or clinical symptoms. Severe cardiovascular disease, respiratory system disease, hematologic diseases and cancer.

  • Serious suicide attempts.

    • Pregnancy or lactation.

      • Modified electroconvulsive therapy (MECT) therapy in the past 1 month. ⑤ Known current psychosis as determined by the DSM-5 or a history of a non-mood psychotic disorder.

        • Participation in another clinical trial concurrently or no more than 1 month prior to randomization.

          • Previously had a severe allergic reaction or immune system disease; ⑧ Using an anti-inflammatory drug or immunosuppressive agent; ⑨ HAMD-17 item 3 (suicide) score: ≥3

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SSRI + golimumab; Participants will be administered with SSRI+golimumab . Golimumab will be administered at the dose of 50mg every month during the acute phase.	Drug: SSRI + golimumab; Golimumab will be administered at the dose of 50mg every month during the acute phase.
Active Comparator: SSRI +placebo; Participants will be administered with SSRI+placebo	Other: SSRI + placebo; placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
remission of acute phase	The primary outcome is defined as changes in HAMD-17 between baseline and 12weeks scored 7 or lower on the Hamilton's Depression Scale with 17 items	12 weeks

Collaborators and Investigators

• Sponsor: Shanghai Mental Health Center

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2020
• Primary Completion (Anticipated): September 30, 2022
• Study Completion (Anticipated): September 30, 2022

Study Registration Dates

• First Submitted: August 16, 2020
• First Submitted That Met QC Criteria: August 25, 2020
• First Posted (Actual): August 28, 2020

Study Record Updates

• Last Update Posted (Actual): August 28, 2020
• Last Update Submitted That Met QC Criteria: August 25, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Anti-Inflammatory Agents; Immunosuppressive Agents; Immunologic Factors; Tumor Necrosis Factor Inhibitors; Golimumab
• Other Study ID Numbers: smhcgxy

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No