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

NCT ID: NCT01483053

Last Updated: 2013-12-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-01-31

Study Completion Date

2015-02-28

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Major Depressive Disorder (MDD)

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

Major depressive disorder Sympathetic nervous system activation Cardiovascular risk factors Agomelatine Escitalopram

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

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.

Group Type ACTIVE_COMPARATOR

Agomelatine

Intervention Type DRUG

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.

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.

Group Type ACTIVE_COMPARATOR

Escitalopram

Intervention Type DRUG

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.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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.

Intervention Type DRUG

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 Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Valdoxan Lexapro Various generics, for example: Esitalo Esipram Escicor Lexam Loxalate

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.

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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Servier Laboratories (Australia) Pty Ltd

UNKNOWN

Sponsor Role collaborator

The Alfred

OTHER

Sponsor Role collaborator

Monash Medical Centre

OTHER

Sponsor Role collaborator

Baker Heart and Diabetes Institute

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Gavin Lambert

Role: STUDY_DIRECTOR

Baker IDI Heart & Diabetes Institute

David Barton

Role: PRINCIPAL_INVESTIGATOR

Monash Medical Centre

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Monash Medical Centre - Monash Health

Clayton, Victoria, Australia

Site Status

Alfred and Baker Medical Unit - Alfred Hospital

Melbourne, Victoria, Australia

Site Status

Baker IDI Heart & Diabetes Institute

Melbourne, Victoria, Australia

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Australia

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Sarah Tremethick

Role: CONTACT

Phone: +61 3 8532 1145

Email: [email protected]

Jennifer Grigo

Role: CONTACT

Phone: +61 3 8531 1166

Email: [email protected]

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

498/11

Identifier Type: -

Identifier Source: org_study_id