RESIST: Understanding the Role of Depression in Heart Disease

Resist: What Are the Mechanisms Involved in Depression and Antidepressant Resistance That Increase Cardiovascular Risk?

This study will investigate the biological pathways involved in anti-depressant resistance that increase risk of cardiovascular disease in people with depression.

Study Overview

• Status: Completed
• Conditions: Depression

Detailed Description

Rationale: Depression is known to be associated with the development of cardiovascular disease and poorer prognosis after cardiac events, however the mechanisms that mediate these links are poorly understood. Inflammatory and neuroendocrine processes are thought to play an important role in this relationship. In addition, antidepressants have been shown to improve cardiac outcomes and have anti-inflammatory effects, whilst inflammation has been shown to be elevated in patients who do not respond to treatment. Several possible biomarkers for antidepressant resistance have also been demonstrated to be cardiovascular risk markers. These include acute phase inflammatory markers, such as interleukin-6 (IL-6), and hypothalamic-pituitary-adrenal axis (HPA) dysregulation.

Design: This will be conducted alongside a larger pharmacological trial, PANDA, where participants will be recruited from primary care and randomized to sertraline (SSRI) or placebo. The RESIST study will compare inflammatory cardiovascular risk factors between depressed patients taking sertraline, depressed patients taking placebo and healthy controls. This will be achieved by investigating the pharmacological effect of antidepressants on gene expression, glucocorticoid and mineralocorticoid receptor function and regulatory T cell (Treg) profiles.

• Study Type: Observational
• Enrollment (Actual): 90

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom
    • University College London

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 74 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Depressed patients will be recruited from the PANDA trial. Healthy controls will be recruited from primary care.

Description

Inclusion Criteria:

• Depressed patients:

  • Meet ICD10 criteria from the Clinical Interview Schedule-Revised (CIS-R)

Exclusion Criteria:

• Depressed patients:

  • Are taking any anti-inflammatory drugs or drugs which interfere with HPA-axis function, endothelial function, circadian rhythm or any other pathways under investigation
  • Unable to read, understand and/or complete questionnaires
  • Other psychiatric disorders: psychosis, schizophrenia, bipolar disorder, mania, hypomania, dementia, and eating disorder
  • Vulnerable adults

• Healthy controls:

  • Have a history of depression
  • Are taking any anti-inflammatory drugs or drugs which interfere with HPA-axis function, endothelial function or circadian rhythm or any other pathways under investigation
  • Unable to read, understand and/or complete questionnaires
  • Other psychiatric disorders: psychosis, schizophrenia, bipolar disorder, mania, hypomania, dementia, and eating disorder
  • Vulnerable adults

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Depressed patients taking sertraline; Patients with depression who have been randomised to the sertraline arm in the PANDA trial
Depressed patients taking placebo; Patients with depression who have been randomised to the placebo arm in the PANDA trial
Healthy controls; Healthy participants with no history of depression

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Candidate gene expression	Levels of RNA expression for genes associated with cardiovascular risk	6 weeks
Glucocorticoid and mineralocorticoid receptor function	Glucocorticoid and mineralocorticoid inhibition of lipopolysaccharide (LPS)-stimulated IL-6 levels.	6 weeks
Regulatory T-cell profiles	Measurement of percentages of leukocyte subsets	6 weeks

Collaborators and Investigators

• Sponsor: University College, London
• Collaborators: British Heart Foundation
• Investigators: Principal Investigator: Glyn Lewis, UCL

Study record dates

Study Major Dates

• Study Start: June 1, 2016
• Primary Completion (ACTUAL): December 1, 2017
• Study Completion (ACTUAL): November 1, 2018

Study Registration Dates

• First Submitted: January 14, 2016
• First Submitted That Met QC Criteria: January 14, 2016
• First Posted (ESTIMATE): January 18, 2016

Study Record Updates

• Last Update Posted (ACTUAL): March 26, 2020
• Last Update Submitted That Met QC Criteria: March 25, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder
• Other Study ID Numbers: 15/0860

Plan for Individual participant data (IPD)

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