The effect of agomelatine on CLOCK gene expression in patients with major depressive disorder and healthy controls: an exploratory study.

Phase 1

• Conditions: Major depressive disorder (MDD), Seasonal affective disorder (subtype of MDD); MedDRA version: 12.1Level: LLTClassification code 10012378Term: Depression

• Registration Number: EUCTR2010-021044-17-AT
• Lead Sponsor: Medizinische Universität Wien

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-08-02
• Last Update Posted: 27 August 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

All subjects:
•Female or male
•Caucasian
•Age 18-65 years
•Blood pressure <160/100 (measured after 5 minutes in supine position)
•Healthy defined as absence of relevant disease or laboratory findings as defined by the investigator
•Signed informed consent
•Ability to comprehend the full nature and purpose of the study
•Negative pregnancy test at screening in women with childbearing potential
•No jet lag, shift work, sleep disorders according to ICD 10 or other events interfering with the chronobiological routine within 2 weeks preceding the first study day.
•No participation in drug trials within 1 month before the first study day.
•No high risk of suicide or a previous suicide attempt within 6 months before the first study day (score >2 on HDRS item 3).

Study group 1 (healthy volunteers)
•No intake of psychotropic drugs within the preceding month
•Global seasonality score (GSS) lower than 6
•No personal or family history (parents and siblings) of affective disorders or relevant diseases, as defined by the investigator (according to MINI (Sheehan et al., 1998)

Study group 2 (Patients with MDD including SAD)
•Fulfilled criteria for a moderate or severe episode of recurrent major depressive disorder (296.32, 296.33) assessed with Structured Clinical Interview for the DSM-IV (SCID) (First et al., 1996). Furthermore patients with SAD must fulfill the criteria for the seasonal pattern specifier according to the DSM-IV-TR
•Healthy defined as absence of relevant laboratory findings or disease other than MDD (including SAD) as defined by the investigator.
•total Hamilton Depression Rating score (HDRS) of >12
Structured Interview Guide for the Hamilton Depression Rating Scale,
(HDRS, 21 items, Hamilton, 1960)
•No axis-I co morbidity (according to MINI) (Sheehan et al., 1998)
•No intake of psychotropic drugs during the following timeframes before the first study day:
-1 week for most antidepressants (including herbal medication), zolpidem and zopiclone, systemic corticosteroids, ACTH, central alpha-adrenergic agonists, reserpine, methyldopa, exogenous melatonin, and opioides;
-2 weeks for nonselective MAO inhibitors, benzodiazepines, and buspirone;
-3 weeks for fluoxetine (if the duration of treatment had been longer than 7 days);
-4 weeks for lithium, antiepileptics, barbiturates, and antipsychotics;
-6 months for long-acting depot neuroleptics.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

2.5.3Exclusion criteria
•History of relevant diseases as defined by the investogator
•Known affective disorder (healthy subjects only)
•HIV or Hepatitis B/C positive virology
•Any drug intake 1 week prior to the first study day (excluding hormonal contraceptives)
•No stable intake of concomitant medication (other than psychotropic drugs) during 4 weeks prior to study day 1.
•Presence of relevant illness within the last 3 weeks
•Suspected non-compliance with study instructions and life-style requirements
•Alcohol or drug abuse
•Blood/Plasma donation within 4 weeks prior to the study day
•Healthy subjects with a subsyndromal SAD or a out of range” result in the
Neuropsychological test
•High risk of suicide or a previous suicide attempt within 6 months before the first study day (score >2 on HDRS item 3).
•Pregnant or lactating women

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Rhythmic 24hour mRNA expression of CLOCK genes, <br>differences in transcript levels of CLOCK genes,<br>differences in the genome-wide gene expression,<br>assessed in mRNA from peripheral blood leucocytes.<br>;Secondary Objective: Patients with MDD will be post hoc stratified, based on the DSM-IV seasonal pattern specifier (gene expression profiles before and after agomelatine treatment will be compared between MDD and SAD) <br>;Primary end point(s): Differences in leucocyte gene expression between healthy subjects and patients before and after agomelatine treatment over 14 days including:<br>•Rhythmic 24hour mRNA expression of CLOCK genes <br>•Differences in transcript levels of specific CLOCK genes<br>•Differences in the genome-wide gene expression<br>