Clinical trial NCT02657798: RESIST: Understanding the Role of Depression in Heart Disease
Official title: Resist: What Are the Mechanisms Involved in Depression and Antidepressant Resistance That Increase Cardiovascular Risk?
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Depression
Lead sponsor: University College, London
Sponsor class: OTHER
Collaborators: name: British Heart Foundation
First posted: 2016-01-18
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: OTHER
Time perspective: CROSS_SECTIONAL
Sampling method: PROBABILITY_SAMPLE
Study population: Depressed patients will be recruited from the PANDA trial. Healthy controls will be recruited from primary care.

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

Eligibility criteria: 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

Primary outcomes:
measure: Candidate gene expression
timeFrame: 6 weeks
measure: Glucocorticoid and mineralocorticoid receptor function
timeFrame: 6 weeks
measure: Regulatory T-cell profiles
timeFrame: 6 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: University College London
Study officials:
affiliation: UCL
name: Glyn Lewis
role: PRINCIPAL_INVESTIGATOR
References: