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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01568307




Registration number
NCT01568307
Ethics application status
Date submitted
25/03/2012
Date registered
2/04/2012
Date last updated
14/09/2023

Titles & IDs
Public title
Major Depressive Disorder - Understanding The Link Between The Brain And The Heart
Scientific 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
Secondary ID [1] 0 0
1022791
Secondary ID [2] 0 0
74/12
Universal Trial Number (UTN)
Trial acronym
MDD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Major Depressive Disorder 0 0
Condition category
Condition code
Mental Health 0 0 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Participants will be prescribed an approved selective serotonin re-uptake inhibitor (SSRI) antidepressant.

Treatment: Drugs: 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).
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Proportion of MDD patients carrying the s allele of the 5-HTT transporter that have higher sympathetic activity than homozygous ll patients.
Timepoint [1] 0 0
up to 12 weeks
Secondary outcome [1] 0 0
To determine the association between sympathetic activity and left ventricular hypertrophy.
Timepoint [1] 0 0
Baseline
Secondary outcome [2] 0 0
Change from baseline in the magnitude of morning surge in blood pressure.
Timepoint [2] 0 0
Baseline and following 12 weeks of antidepressant treatment.
Secondary outcome [3] 0 0
Change from baseline in insulin resistance.
Timepoint [3] 0 0
Baseline and following 12 weeks of antidepressant treatment.
Secondary outcome [4] 0 0
Change from baseline on markers of cardiac risk.
Timepoint [4] 0 0
Baseline and following 12 weeks of antidepressant treatment.

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/05/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/12/2020
Sample size
Target
80
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Ballarat Health Service Psychiatric Services - Ballarat
Recruitment hospital [2] 0 0
Monash Medical Centre - Monash Health - Clayton
Recruitment hospital [3] 0 0
Alfred and Baker Medical Unit - Alfred Hospital - Melbourne
Recruitment hospital [4] 0 0
Baker IDI Heart & Diabetes Institute - Melbourne
Recruitment postcode(s) [1] 0 0
3350 - Ballarat
Recruitment postcode(s) [2] 0 0
3168 - Clayton
Recruitment postcode(s) [3] 0 0
3004 - Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
Baker Heart and Diabetes Institute
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
The Alfred
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Monash Medical Centre
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Ballarat Health Services
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01568307
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Gavin Lambert
Address 0 0
Baker IDI Heart & Diabetes Institute
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01568307