Major Depressive Disorder - Understanding The Link Between The Brain And The Heart

NCT01568307 | Completed Phase 4

• 2 other identifiers: 74/121022791
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 4

Brief Summary

There is strong evidence that patients with major depressive disorder (MDD) have an increased risk of developing coronary heart disease (CHD). This elevated risk is independent of standard risk factors such as smoking, obesity, high cholesterol, diabetes, and high blood pressure. The relative risk of developing CHD is proportional to the severity of depression (the more severe the depression, the more likely the development of CHD). The sympathetic nervous system (the part of your nervous system that makes your heart beat harder and faster) is responsible for our "flight and fight" response to a threatening situation. It has been determined that increased sympathetic nervous system activation occurs in approximately one in three untreated patients with MDD (with no underlying CHD). There is growing evidence linking elevated sympathetic activity to early stages of kidney dysfunction and an increased incidence of cardiovascular (heart and blood vessel) disease development (eg, heart attacks). Sympathetic nervous system activation over a prolonged period of time may also be associated with abnormal blood pressure regulation and the development of insulin resistance (an important feature of type 2 diabetes). It has been suggested that a certain gene, known as the serotonin transporter (5-HTT) gene, may be involved. In particular, work from our group indicates that a particular type of this gene, the short form (or "short" allele) may be important in linking MDD, sympathetic nervous activation, and increased cardiac risk. This study aims to examine the role of the 5-HTT gene on cardiovascular risk factors associated with elevated sympathetic activity in patients with MDD. Additionally, the study will examine the effect of serotonin re-uptake inhibitor (SSRI) therapy on these parameters. A clearer understanding of these systems and processes will allow for identification of patients with increased cardiac risk and development of risk reduction strategies. Such information is clinically significant given the link between cardiovascular disease and MDD. Hypothesis 1: That MDD patients carrying the s allele of the 5-HTT transporter have higher sympathetic activity than homozygous ll patients. Hypothesis 2: that MDD patients with elevated sympathetic activity display early signs of left ventricular hypertrophy (LVH) and diastolic dysfunction. Hypothesis 3: That MDD patients with high sympathetic activity have greater morning surges in blood pressure than patients with normal sympathetic activity. Hypothesis 4: That MDD patients with elevated sympathetic activity display early signs of insulin resistance. Hypothesis 5: That SSRI therapy, in particular in those who carry the s allele of the 5-HTT, has a favourable effect on blood pressure variability and morning surge in blood pressure, sympathetic stress reactivity, and markers of insulin resistance.

Conditions

Major Depressive Disorder

Keywords

Major depressive disorder; Serotonin transporter; Sympathetic nervous system activation; Cardiovascular risk factors; Serotonin re-uptake inhibitor

Outcome Measures

Primary Outcomes (1)

• Proportion of MDD patients carrying the s allele of the 5-HTT transporter that have higher sympathetic activity than homozygous ll patients.

  Participants will be prescribed an approved SSRI in line with standard practice.The investigators will explore the association between the degree of sympathetic nervous activation and 5-HTT genotype in patients with MDD. They do not plan to examine the role of the 5-HTT genotype on MDD development. They will examine the relationship between the degree of sympathetic nervous system activity and early signs of cardiac structure and function abnormalities, insulin resistance, and morning surge in blood pressure. This may help in identifying MDD patients who are at an increased risk.

  up to 12 weeks

Secondary Outcomes (4)

• To determine the association between sympathetic activity and left ventricular hypertrophy.

  Baseline

• Change from baseline in the magnitude of morning surge in blood pressure.

  Baseline and following 12 weeks of antidepressant treatment.

• Change from baseline in insulin resistance.

  Baseline and following 12 weeks of antidepressant treatment.

• Change from baseline on markers of cardiac risk.

  Baseline and following 12 weeks of antidepressant treatment.

Interventions

Participants will be prescribed an approved selective serotonin re-uptake inhibitor (SSRI) antidepressant. DRUG

The choice of SSRI will be based on clinical judgement and prescribed in line with standard dosing approved by the Therapeutic Goods Administration (TGA).

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18-70 years.
• Capable of understanding and willing to provide signed and dated written, voluntary informed consent in advance of any protocol-specific procedures.
• MDD or MDD with melancholia according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria. Patients with comorbid panic or anxiety disorders will be included if MDD is the primary diagnosis.
• Hamilton Depression (HAM D) \> 18.
• Beck Depression Inventory (BDI-II) \> 18.

You may not qualify if:

• Aged \< 18 or \> 70 years.
• Current antidepressant treatment.
• Previous failed response to SSRI treatment at the maximum tolerated dose for at least 4 weeks.
• Known or suspected hypersensitivity to the prescribed antidepressant or any of its ingredients.
• Current high suicide risk.
• Comorbid panic or anxiety disorders as the primary diagnosis.
• Pre-existing and/or current diagnosed heart disease.
• Comorbid medical conditions including type 1 diabetes, medicated hypertension, epilepsy, bleeding disorders, alcohol/drug dependence, infectious blood diseases, psychotic disorders, personality disorders, eating disorders, mental retardation, dementia (ie, Mini Mental State Examination \[MMSE\] \< 23), or gastrointestinal illness or previous bariatric (weight loss) surgery that may impair antidepressant absorption.
• Clinically significant abnormalities on examination or laboratory testing and clinically significant medical conditions not listed above that are serious and/or unstable.
• Pregnant or breastfeeding women.
• Women of childbearing potential (WOCP) who are not using medically accepted contraception (ie, intrauterine devices \[IUDs\], hormonal contraceptives \[oral, depot, patch or injectable\], and double barrier methods such as condoms or diaphragms with spermicidal gel or foam). Women who are postmenopausal (amenorrhea for at least 12 consecutive months) or surgically sterile are not considered to be WOCP.

Sponsors & Collaborators

• Baker Heart and Diabetes Institute: lead
• The Alfred: collaborator
• Monash Medical Centre: collaborator
• Ballarat Health Services: collaborator

Study Sites (4)

Ballarat Health Service Psychiatric Services

Ballarat, Victoria, 3350, Australia

Location

Monash Medical Centre - Monash Health

Clayton, Victoria, 3168, Australia

Location

Alfred and Baker Medical Unit - Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

Baker IDI Heart & Diabetes Institute

Melbourne, Victoria, 3004, Australia

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Selective Serotonin Reuptake Inhibitors; Antidepressive Agents

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Neurotransmitter Agents; Serotonin Agents; Physiological Effects of Drugs; Psychotropic Drugs; Central Nervous System Agents; Therapeutic Uses

Study Officials

• Gavin Lambert

  Baker IDI Heart & Diabetes Institute

  STUDY DIRECTOR

• David Barton

  Monash Medical Centre

  PRINCIPAL INVESTIGATOR

• Abdul Khalid

  Ballarat Health Services

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2012
• First Posted: April 2, 2012
• Study Start: May 1, 2012
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2020
• Last Updated: September 14, 2023

Record last verified: 2018-11

Locations

AU (4)