Major Depressive DisorderPhase 4MDDNCT01568307
Major Depressive Disorder - Understanding The Link Between The Brain And The Heart
A Phase 4 study testing Participants will be prescribed an approved selective serotonin re-uptake inhibitor (SSRI) antidepressant. in people with Major Depressive Disorder, run by Baker Heart and Diabetes Institute at 4 sites in Australia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- Participants will be prescribed an approved selective serotonin re-uptake inhibitor (SSRI) antidepressant.
- How many people
- 80 participants
- Where
- 4 sitesAustralia
- Study dates
- May 2012to Dec 2020
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
4 sites in 1 country.
Australia4 sites
Ballarat Health Service Psychiatric Services
Ballarat, Victoria, 3350
Monash Medical Centre - Monash Health
Clayton, Victoria, 3168
Alfred and Baker Medical Unit - Alfred Hospital
Melbourne, Victoria, 3004
Baker IDI Heart & Diabetes Institute
Melbourne, Victoria, 3004
About this study
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
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).
Read more
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
- Being tested
- Participants will be prescribed an approved selective serotonin re-uptake inhibitor (SSRI) antidepressant.
- Keywords
- Major depressive disorder, Serotonin transporter, Sympathetic nervous system activation, Cardiovascular risk factors, Serotonin re-uptake inhibitor
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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).
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: up to 12 weeks
Secondary outcomes (4)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline and following 12 weeks of antidepressant treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2012 (estimated)
- Study startMay 2012
- Primary completionDec 2020
- Study completionDec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Baker Heart and Diabetes Institute
- Sponsor type
- University, hospital or other
- Collaborators
- The Alfred, Monash Medical Centre, Ballarat Health Services
- Responsible party
- Sponsor
- Investigators
- Gavin Lambert, Study director, Baker IDI Heart & Diabetes InstituteDavid Barton, Principal investigator, Monash Medical CentreAbdul Khalid, Principal investigator, Ballarat Health Services
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01568307
- Sponsor's protocol ID
- 74/12
- Other IDs
- 1022791
- Acronym
- MDD
- Status last verified
- Nov 2018
- First submitted
- 25 Mar 2012
- Last updated
- 14 Sep 2023
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01568307
- Acronym / sponsor ID
- MDD / 74/12
- Conditions
- Major Depressive Disorder
- Keywords
- Major depressive disorder, Serotonin transporter, Sympathetic nervous system activation, Cardiovascular risk factors, Serotonin re-uptake inhibitor
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Baker Heart and Diabetes InstituteUniversity, hospital or other
- Collaborators
- The Alfred, Monash Medical Centre, Ballarat Health Services
- Study start
- May 2012
- Primary completion
- Dec 2020 (actual)
- Study completion
- Dec 2020 (actual)
- First posted
- 2 Apr 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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). | Drug | – |
Primary outcome
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
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.
4 secondary outcomes
To determine the association between sympathetic activity and left ventricular hypertrophy.
Time frame: Baseline
Change from baseline in the magnitude of morning surge in blood pressure.
Time frame: Baseline and following 12 weeks of antidepressant treatment.
Change from baseline in insulin resistance.
Time frame: Baseline and following 12 weeks of antidepressant treatment.
Change from baseline on markers of cardiac risk.
Time frame: Baseline and following 12 weeks of antidepressant treatment.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gavin Lambert study director
Baker IDI Heart & Diabetes Institute
David Barton principal investigator
Monash Medical Centre
Abdul Khalid principal investigator
Ballarat Health Services
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Participants will be prescribed an approved selective serotonin re-uptake inhibitor (SSRI) antidepressant. in people with Major Depressive Disorder, run by Baker Heart and Diabetes Institute at 4 sites in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Sep 2023.