A Phase 4 interventional study of Participants will be prescribed an approved selective serotonin re-uptake inhibitor (SSRI) antidepressant. in Major Depressive Disorder, sponsored by Baker Heart and Diabetes Institute. Completed at 4 sites in Australia. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2023-09-14.
Sponsored by Baker Heart and Diabetes Institute · Phase 4, Interventional, and Treatment
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.
4,845 studies on the registry are indexed under Depressive Disorder; 514 are open to participants now.
This study's planned enrollment of 80 is close to the median of 80 across 3,999 interventional studies indexed under Depressive Disorder.
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Exclusion Criteria:
The choice of SSRI will be based on clinical judgement and prescribed in line with standard dosing approved by the Therapeutic Goods Administration (TGA).
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.
Time frame: up to 12 weeks
To determine the association between sympathetic activity and left ventricular hypertrophy.
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.
Time frame: Baseline
Change from baseline in the magnitude of morning surge in blood pressure.
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.
Time frame: Baseline and following 12 weeks of antidepressant treatment.
Change from baseline in insulin resistance.
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.
Time frame: Baseline and following 12 weeks of antidepressant treatment.
Change from baseline on markers of cardiac risk.
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.
Time frame: Baseline and following 12 weeks of antidepressant treatment.
This study is completed, as verified in Nov 2018. You cannot join it, but the record below documents what was studied.
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Baker Heart and Diabetes Institute