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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01483053

Registration number

NCT01483053

Ethics application status

Date submitted

27/11/2011

Date registered

1/12/2011

Date last updated

18/12/2013

Titles & IDs

Public title

Cardiovascular Effects of Agomelatine and Escitalopram in Patients With Major Depressive Disorder (MDD)

Scientific title

A Randomised Trial Investigating the Cardiovascular Effects of Agomelatine and Escitalopram in Patients With Major Depressive Disorder.

Secondary ID [1]

498/11

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Major Depressive Disorder (MDD)

Condition category

Condition code

Mental Health

Depression

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Treatment: Drugs - Agomelatine
Treatment: Drugs - Escitalopram

Active comparator: Agomelatine - Participants who are randomly assigned to the agomelatine group will be treated with agomelatine oral tablets for twelve weeks. Participants will begin their agomelatine treatment at 25mg/day dosage, increasing to 50mg/day as clinically indicated.

Active comparator: Escitalopram - Participants who are randomly assigned to the escitalopram group will be treated with escitalopram oral tablets for twelve weeks. Participants will begin their escitalopram treatment at 10mg/day dosage, increasing to 20mg/day as clinically indicated.

Treatment: Drugs: Agomelatine
Participants who are randomly assigned to the agomelatine group will be treated with agomelatine oral tablets for twelve weeks. Participants will begin their agomelatine treatment at 25mg/day dosage, increasing to 50mg/day as clinically indicated.

Treatment: Drugs: Escitalopram
Participants who are randomly assigned to the escitalopram group will be treated with escitalopram oral tablets for twelve weeks. Participants will begin their escitalopram treatment at 10mg/day dosage, increasing to 20mg/day as clinically indicated.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Control group

Outcomes

Primary outcome [1]

Change from baseline in markers of sympathetic nervous system activity.

Timepoint [1]

Baseline and following 12 weeks of antidepressant treatment.

Secondary outcome [1]

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

Timepoint [1]

Baseline and following 12 weeks of antidepressant treatment.

Secondary outcome [2]

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

Timepoint [2]

Baseline

Secondary outcome [3]

Change from baseline in insulin resistance.

Timepoint [3]

Baseline and following 12 weeks of antidepressant treatment.

Secondary outcome [4]

Change from baseline on markers of cardiac risk.

Timepoint [4]

Baseline and following 12 weeks of antidepressant treatment.

Eligibility

Key inclusion criteria

* Aged 18-65 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

65 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

* Aged < 18 or > 65 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 either escitalopram or agomelatine or any of their 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, hepatic impairment (cirrhosis or active liver disease), 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.
* Participants on betablockers (for example, metoprolol).
* Participants currently taking the following contraindicated medications for agomelatine and/or escitalopram:

* Cytochrome (CYP) P450 1A2 inhibitors (e.g. fluvoxamine, ciprofloxacin)
* Monoamine Oxidase Inhibitors;

* Irreversible non-selective monoamine oxidase inhibitors (MAOIs)
* Reversible, selective MAO-A inhibitor (e.g. moclobemide)
* Reversible, non-selective MAOI (e.g. linezolid)
* Pimozide

Participants who are eligible to take part in the study are prohibited to take the contraindicated medications listed above for the entire duration of the study.

* 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 (ie, amenorrhea for at least 12 consecutive months) or surgically sterile are not considered to be WOCP.
* Sexually active men with WOCP partners who are not using medically accepted contraception.

Medically accepted contraception for women and sexually active men with WOCP partners will be continued throughout the study and for 30 days after the last antidepressant dose.

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

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

Parallel

Other design features

Phase

Phase 4

Type of endpoint/s

Statistical methods / analysis

Recruitment

Recruitment status

UNKNOWN

Data analysis

Reason for early stopping/withdrawal

Other reasons

Date of first participant enrolment

Anticipated

Actual

1/01/2014

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

1/02/2015

Actual

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

Monash Medical Centre - Monash Health - Clayton

Recruitment hospital [2]

Alfred and Baker Medical Unit - Alfred Hospital - Melbourne

Recruitment hospital [3]

Baker IDI Heart & Diabetes Institute - Melbourne

Recruitment postcode(s) [1]

3168 - Clayton

Recruitment postcode(s) [2]

3004 - Melbourne

Funding & Sponsors

Primary sponsor type

Other

Name

Baker Heart and Diabetes Institute

Address

Country

Other collaborator category [1]

Other

Name [1]

Servier Laboratories (Australia) Pty Ltd

Address [1]

Country [1]

Other collaborator category [2]

Other

Name [2]

The Alfred

Address [2]

Country [2]

Other collaborator category [3]

Other

Name [3]

Monash Medical Centre

Address [3]

Country [3]

Ethics approval

Ethics application status

Summary

Brief summary

There is strong evidence that patients with major depressive disorder (MDD) are at increased risk of developing coronary heart disease (CHD). This elevated risk is independent of classical risk factors such as smoking, obesity, hypercholesterolemia, diabetes and hypertension. The risk of CHD is increased 1½-2 fold in those with minor depression and 3-4½ fold in subjects with MDD. Put simply, the relative risk of developing CHD is proportional to the severity of the depression. While the mechanism of increased cardiac risk attributable to MDD is not known disturbances in autonomic function most likely do play a part.

In untreated patients with MDD (with no underlying CHD) the investigators have identified that a marked sympathetic nervous activation and diminished heart rate variability (HRV) occurs in a proportion (approximately one third) of patients. Diminished HRV has been linked to increased incidence rates of acute cardiac events in conditions such as hypertension, diabetes and myocardial infarction. Importantly, whether treating depression actually improves the risk of: (1) CHD development or (2) recurrence of cardiac events in patients with existing CHD remains unknown.

The investigators, and others, have provided a growing body of evidence linking elevated sympathetic activity and exaggerated sympathetic responses to stress to early stages of end organ dysfunction and markers of disease development. Of particular note, in addition to possible effects on HRV is the association of chronic sympathetic nervous activation to: (a) abnormal blood pressure regulation and (b) the development of insulin resistance.

The investigators therefore plan to examine the cardiovascular effects of two different antidepressant medications, agomelatine and escitalopram, in patients with MDD. In addition, the investigators plan to investigate the effects these two medications have on sympathetic nervous system activity, blood pressure, HRV, endothelial function, metabolic and psychological effects.

Findings from this study will assist us to identify of biological correlates of sympathetic nervous activation which will enable us to: (1) identify those at potentially increased cardiac risk, and (2) potentially implement additional therapeutic strategies in order to reduce cardiac risk. Indeed, it is not known whether antidepressant treatment alone would be sufficient to reverse any adverse effects of sympathetic nervous activation. This study aims to answer this important clinical question.

Trial website

https://clinicaltrials.gov/study/NCT01483053

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Gavin Lambert

Address

Baker IDI Heart & Diabetes Institute

Country

Phone

Fax

Contact person for public queries

Name

Sarah Tremethick

Address

Country

Phone

+61 3 8532 1145

Fax

[email protected]

Contact person for scientific queries

No information has been provided regarding IPD availability

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT01483053

Trial Review

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01483053