The Role of Inflammatory Processes in Development and Treatment of Depression (INFLAME-D)

An Investigation of the Role of Inflammatory Processes in the Development and Treatment of Idiopathic Unipolar and Bipolar Depression in Patients With Moderate to Severe Depressive Symptoms.

The study investigates the influence of inflammatory processes on the development and the course of uni- and bipolar depression. It is assumed, that the concentrations of certain inflammatory proteins have an influence on the development of depression, its clinical severity, the response to treatment and the risk of relapse. To verify this hypothesis, a total of 145 patients, which were hospitalized für treatment of a depressive disorder in the study centers in Germany, Italy and France, were screened according to the criteria set out in the study protocol. Finally, 104 patients with moderate to severe depressive symptoms were included in the study. These patients were treated according to the recommendations of the DGPPN treatment guidelines. All patients received a medication with sertraline or venlafaxine during the study, starting at baseline. The patients were examined for the presence and severity of depressive symptoms at the time of study enrollment, as well as after 4 and 8 weeks, using standardized clinical test procedures. In addition blood was taken. In the serum of the patients, the concentrations of specific inflammatory proteins were measured using Cytometric Bead Array (CBA) and Enzyme-linked Immunosorbent Assay (ELISA) and then correlated with the clinical data. The investigated proteins include high-sensitivity CRP (C-Reactive-Protein), Interleukin 4, Interleukin 6, Interleukin 12, tumor necrosis factor-α, Eotaxin, Intercellular adhesion molecule 1 (CD54), Interferone-gamma and monocyte chemotactic protein 1 (MCP-1).

Study Overview

• Status: Completed
• Conditions: Depressive Disorder; Depression; Inflammation
• Intervention / Treatment: Drug: Sertraline or venlafaxine; Diagnostic test: Immune parameters

Detailed Description

The study investigates the influence of inflammatory processes on the development and the course of uni- and bipolar depression. It is assumed, that the concentrations of certain inflammatory proteins have an influence on the development of depression, its clinical severity, the response to treatment and the risk of relapse. To verify this hypothesis, a total of 145 patients, which were hospitalized für treatment of a depressive disorder in the study centers in Germany, Italy and France, were screened according to the criteria set out in the study protocol. Finally, 104 patients with moderate to severe depressive symptoms were included in the study. The severity of the symptoms was classified using well-established clinical rating scales like Montgomery-Asberg Depression Rating Scale (MADRS) and Hamilton rating scale for depression (HAMD). All enrolled patients were treated according to the recommendations of the German Association for Psychiatry, Psychotherapy and Psychosomatics (DGPPN) treatment guidelines.

In order to make drug-induced changes in the serum concentrations of the examined proteins as comparable as possible, it was determined in advance, that all patients should be treated with either sertraline (first choice) or venlafaxine (second choice) as an oral antidepressant. Apart from that, the antidepressive therapy, ie psychotherapy and similar procedures, had not been standardized. The treatment of study participants did not differ from the treatment of other patients hospitalized because of depression, who did not participate in the study. The patients were examined for the presence and severity of depressive symptoms at the time of study enrollment, as well as after 4 and 8 weeks, using standardized clinical test procedures. In addition blood was taken. In the serum of the patients, the concentrations of specific inflammatory proteins were measured using Cytometric Bead Array (CBA) and Enzyme-linked Immunosorbent Assay (ELISA) and then correlated with the clinical data. The investigated proteins include high-sensitivity CRP (C-Reactive-Protein), Interleukin 4, Interleukin 6, Interleukin 12, tumor necrosis factor-α, Eotaxin, Intercellular adhesion molecule 1 (CD54), Interferone-gamma and monocyte chemotactic protein 1 (MCP-1).

• Study Type: Observational
• Enrollment (Actual): 104

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with pharmacological treatment of depressive symptoms (out- or inpatient treatment).

Description

Inclusion Criteria:

• Patients with uni- or bipolar depression, diagnosed according to the criteria of the Diagnostic and Statistical Manual Version IV (DSM-IV) via Mini-international neuropsychiatric interview Version 6.0 (MINI 6.0) diagnostic tool.
• At the time of inclusion in the study, the symptoms must meet at least the requirements of a moderately severe depression, defined by a minimum score of ≥ 22 on the Montgomery-Asberg Depression Scale.

Exclusion Criteria:

• Patients with severe somatic, rheumatic, endocrine or neurological comorbidities. This includes in particular neurological disorders associated with cognitive disorder, severe liver, kidney and cardiac diseases.
• Patients, who are being treated permanently with anti-inflammatory or immunosuppressive drugs (e.g. corticosteroids or alpha / beta-a(nta)gonists, immuno suppressant drugs).
• Patients with severe psychiatric disorders (Axis I) such as schizophrenia, dementia, attention deficit hyperactivity disorder, obsessive-compulsive disorder, current alcohol, drugs or drug addiction.
• Patients who have already been treated unsuccessfully with sertraline and all alternate medications allowed in the study.
• Pregnant or lactating (breast feeding) women.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

TAU (treatment as usual) group; Patients with depression, meeting inclusion criteria, who needed antidepressant treatment and received either sertraline or venlafaxine.

Drug: Sertraline or venlafaxine; Patients were treated as needed with sertraline or venlafaxine following the official guidelines, starting with a dose of 25 mg/d or respectively 37,5 mg/day. The starting dose could be increased during the course of the treatment as clinically needed according to guide lines.; Diagnostic test: Immune parameters; Serum was taken before, during an after treatment for measurement of different immune parameters.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in severity of depressive symptoms	Measurement of depressive symptoms using the Montgomery-Asberg Depression Rating Scale. The scale measures the severity of depression-associated symptoms. The usual cutoff points are 0 to 6 - depression absent, 7 to 19 - mild depression, 20 to 34 - moderate depression, >34 severe depression	4 and 8 weeks after enrollment in the study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in serum-concentration of inflammatory proteins	measurement of inflammatory proteins as listed in description of the study: high-sensitivity CRP (C-Reactive-Protein), Interleukin 4, Interleukin 6, Interleukin 12, tumor necrosis factor-α, Eotaxin, Intercellular adhesion molecule 1 (CD54), Interferone-gamma and monocyte chemotactic protein 1 (MCP-1). All results are given in the unit pg/ml.	4 and 8 weeks after enrollment in the stuy

Collaborators and Investigators

• Sponsor: Kliniken Essen-Mitte
• Collaborators: University of Bordeaux; German Federal Ministry of Education and Research; Ruhr University of Bochum; National Research Agency, France; Ministry of Health, Italy; IRCCS Centro San Giovanni di Dio Fatebenefratelli; Créteil Hospital
• Investigators: Study Director: Martin Schäfer, Kliniken Essen-Mitte

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 5, 2015
• Primary Completion (ACTUAL): March 6, 2018
• Study Completion (ACTUAL): March 6, 2018

Study Registration Dates

• First Submitted: April 16, 2019
• First Submitted That Met QC Criteria: April 16, 2019
• First Posted (ACTUAL): April 19, 2019

Study Record Updates

• Last Update Posted (ACTUAL): February 12, 2020
• Last Update Submitted That Met QC Criteria: February 10, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Pathologic Processes; Mood Disorders; Depression; Depressive Disorder; Inflammation; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Antidepressive Agents, Second-Generation; Serotonin and Noradrenaline Reuptake Inhibitors; Sertraline; Venlafaxine Hydrochloride
• Other Study ID Numbers: EssenMitte

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual patient data (IPD) completely anonymized
• IPD Sharing Time Frame: starting 6 months after publication
• IPD Sharing Access Criteria: the data will be provided for the purpose of meta-analysis to scientific groups and researchers after personal request via the office of the studies director Prof. Martin Schäfer.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

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