Major Depressive Disorder - Understanding The Link Between The Brain And The Heart (MDD)

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by Baker IDI Heart and Diabetes Institute
Sponsor:
Collaborators:
The Alfred
Monash Medical Centre
Ballarat Health Service Psychiatric Services
Information provided by (Responsible Party):
Baker IDI Heart and Diabetes Institute
ClinicalTrials.gov Identifier:
NCT01568307
First received: March 25, 2012
Last updated: December 16, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Major Depressive Disorder
Drug: Participants will be prescribed an approved selective serotonin re-uptake inhibitor (SSRI) antidepressant.
Phase 4

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Interactions Between The Serotonin Transporter And Sympathetic Nervous System Activation In Patients With Major Depressive Disorder - Understanding The Link Between The Brain And The Heart

Resource links provided by NLM:


Further study details as provided by Baker IDI Heart and Diabetes Institute:

Primary Outcome Measures:
  • Proportion of MDD patients carrying the s allele of the 5-HTT transporter that have higher sympathetic activity than homozygous ll patients. [ Time Frame: up to 12 weeks ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • To determine the association between sympathetic activity and left ventricular hypertrophy. [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    The investigators will measure the relationship between sympathetic nervous activity and left ventricular mass in patients with MDD. ECG, ECHO, and blood pressure data will be used to test the hypothesis that MDD patients with elevated sympathetic activity display early signs of LVH and diastolic dysfunction.

  • Change from baseline in the magnitude of morning surge in blood pressure. [ Time Frame: Baseline and following 12 weeks of antidepressant treatment. ] [ Designated as safety issue: No ]
    The investigators will explore the association between sympathetic nervous system activity and stress reactivity to the morning surge in blood pressure in patients with MDD. Blood pressure data will be used to test the hypothesis that MDD patients with high sympathetic activity have greater morning surges in blood pressure than patients with normal sympathetic activity.

  • Change from baseline in insulin resistance. [ Time Frame: Baseline and following 12 weeks of antidepressant treatment. ] [ Designated as safety issue: No ]
    The investigators will explore the association between sympathetic nervous activity and stress reactivity to signs of insulin resistance in patients with MDD. Oral glucose tolerance test data will be used to test the hypothesis that MDD patients with elevated sympathetic activity display early signs of insulin resistance.

  • Change from baseline on markers of cardiac risk. [ Time Frame: Baseline and following 12 weeks of antidepressant treatment. ] [ Designated as safety issue: No ]
    The investigators will explore the association between SSRI therapy and markers of cardiac risk. They will test the hypothesis that SSRI therapy, in particular in those who carry th 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.


Estimated Enrollment: 80
Study Start Date: May 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Participants will be prescribed an approved selective serotonin re-uptake inhibitor (SSRI) antidepressant.
    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

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01568307

Contacts
Contact: Sarah Tremethick +61 3 8532 1145 sarah.tremethick@bakeridi.edu.au
Contact: Jennifer Grigo +61 3 8532 1166 jennifer.grigo@bakeridi.edu.au

Locations
Australia, Victoria
Ballarat Health Service Psychiatric Services Recruiting
Ballarat, Victoria, Australia, 3350
Principal Investigator: Abdul Khalid         
Sub-Investigator: Rajul Tandon         
Sub-Investigator: Arup Dhar         
Sub-Investigator: Sarah Tremethick         
Sub-Investigator: Jennifer Grigo         
Sub-Investigator: Sonia Ghai         
Sub-Investigator: Pella Karalis         
Monash Medical Centre - Monash Health Recruiting
Clayton, Victoria, Australia, 3168
Principal Investigator: David Barton         
Sub-Investigator: Arup Dhar         
Sub-Investigator: Sarah Tremethick         
Sub-Investigator: Jennifer Grigo         
Sub-Investigator: Krishna Vaddadi         
Alfred and Baker Medical Unit - Alfred Hospital Recruiting
Melbourne, Victoria, Australia, 3004
Principal Investigator: Gavin Lambert         
Sub-Investigator: Markus Schlaich         
Sub-Investigator: Elisabeth Lambert         
Sub-Investigator: Murray Esler         
Sub-Investigator: Geoff Head         
Sub-Investigator: Dagmara Hering         
Sub-Investigator: Nina Eikelis         
Sub-Investigator: Carolina Ika Sari         
Sub-Investigator: Petra Marusic         
Sub-Investigator: Toni Rice         
Sub-Investigator: Mariee Grima         
Sub-Investigator: David Barton         
Sub-Investigator: Arup Dhar         
Sub-Investigator: Sarah Tremethick         
Sub-Investigator: Jennifer Grigo         
Sub-Investigator: Donna Vizi         
Sub-Investigator: Louise Hammond         
Baker IDI Heart & Diabetes Institute Recruiting
Melbourne, Victoria, Australia, 3004
Principal Investigator: Gavin Lambert         
Sub-Investigator: Markus Schlaich         
Sub-Investigator: Elisabeth Lambert         
Sub-Investigator: Murray Esler         
Sub-Investigator: Geoff Head         
Sub-Investigator: Dagmara Hering         
Sub-Investigator: Nina Eikelis         
Sub-Investigator: Carolina Ika Sari         
Sub-Investigator: Petra Marusic         
Sub-Investigator: Toni Rice         
Sub-Investigator: Mariee Grima         
Sub-Investigator: David Barton         
Sub-Investigator: Arup Dhar         
Sub-Investigator: Sarah Tremethick         
Sub-Investigator: Jennifer Grigo         
Sub-Investigator: Donna Vizi         
Sub-Investigator: Louise Hammond         
Sponsors and Collaborators
Baker IDI Heart and Diabetes Institute
The Alfred
Monash Medical Centre
Ballarat Health Service Psychiatric Services
Investigators
Study Director: Gavin Lambert Baker IDI Heart & Diabetes Institute
Principal Investigator: David Barton Monash Medical Centre
Principal Investigator: Abdul Khalid Ballarat Health Service Psychiatric Services
  More Information

No publications provided

Responsible Party: Baker IDI Heart and Diabetes Institute
ClinicalTrials.gov Identifier: NCT01568307     History of Changes
Other Study ID Numbers: 74/12, 1022791
Study First Received: March 25, 2012
Last Updated: December 16, 2013
Health Authority: Australia: Human Research Ethics Committee
Australia: Department of Health and Ageing Therapeutic Goods Administration
Australia: National Health and Medical Research Council

Keywords provided by Baker IDI Heart and Diabetes Institute:
Major depressive disorder
Serotonin transporter
Sympathetic nervous system activation
Cardiovascular risk factors
Serotonin re-uptake inhibitor

Additional relevant MeSH terms:
Depressive Disorder, Major
Depressive Disorder
Depression
Disease
Mood Disorders
Mental Disorders
Behavioral Symptoms
Pathologic Processes
Antidepressive Agents
Serotonin
Serotonin Uptake Inhibitors
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Serotonin Receptor Agonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Neurotransmitter Uptake Inhibitors

ClinicalTrials.gov processed this record on September 22, 2014