Clinical trial NCT00386841: Outcome Following Antidepressant Treatment on Possible Endo-Phenotypes for Major Depression
Official title: Associations Between Gene-Polymorphisms, Endo-Phenotypes for Depression and Antidepressive Treatment (AGENDA)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Healthy
Keywords: Major depression
First degree relatives
Escitalopram
Cortisol
Cognition
Personality
Endo-phenotype
Lead sponsor: University of Copenhagen
Sponsor class: OTHER
First posted: 2006-10-12
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: The purpose of this study is to determine whether outcome following antidepressant treatment can be used as a tool to evaluate endo-phenotypes for depression.

Detailed description: The research in depression has for some years focused at the identification of endo-phenotypes. Endo-phenotypes are heritable biological or psychological markers, which are more commonly found in patients and their healthy relatives than in the general population.

Recent studies point at disturbed regulation of the hypothalamic-pituitary-adrenocortical (HPA) system as a possible endo-phenotype for depression.

The hypothesis of AGENDA are that endo-phenotypes are affected by treatment with antidepressants in healthy first degree relatives.

AGENDA is a four week randomized, placebo-controlled, double-blind trial in which first degree relatives of patients with the diagnosis of depression are randomised in to two groups, which are treated with either placebo or antidepressant medicine (Cipralex). We expect to include 80 healthy subjects, with the predisposition for depression, since one of their parents or siblings recently was treated for depression.

The subjects will be examined before and after four weeks of treatment by a thorough interview concerning psychiatric symptoms (SCAN), including depressive symptoms, personality, perceived stress and cognitive function. The effect of antidepressant on stress is measured with saliva-cortisol and by the response to the combined dexamethasone corticotropin-releasing (CRH) hormone test. Additionally, MR and PET scans of the 5-HT4 receptor function will be conducted before and after 4 weeks of treatment.

Eligibility criteria: Inclusion Criteria:

* Offsprings or siblings of patients with major depression
* Born in Denmark with European parents and grandparents
* For women; not pregnant or breastfeeding
* Written informed consent

Exclusion Criteria:

* Somatically illness or other handicaps which make participation in the study impossible
* Daily intake of drugs interfering with corticosteroids or escitalopram
* Hypersensitivity to escitalopram, dexamethasone or human corticotropin-releasing hormone
* Former medical or psychological treatment for diseases in the affective or schizophrenic spectrum
* Ongoing addiction of alcohol or psychoactive drugs

Primary outcomes:
measure: Changes in the response on the combined dexamethasone corticotropin-releasing hormone test before and after 4 weeks treatment with escitalopram or placebo.
timeFrame: 4-6 weeks
Secondary outcomes:
measure: Changes in scores before and after 4 weeks treatment with escitalopram or placebo on: Cognition
timeFrame: 4-6 weeks
measure: Social function
timeFrame: 4-6 weeks
measure: Neuroticism
timeFrame: 4-6 weeks
measure: Subjective; sleep, pain, aggression, depression, anxiety, quality of life, perceived stress and side-effects
timeFrame: 4-6 weeks
measure: Receptor status by PET-scans
timeFrame: 4-6 weeks
measure: Inflammatory parameters
timeFrame: 4-6 weeks
measure: Paraclinical measures
timeFrame: 4-6 weeks
measure: MR and fMRI
timeFrame: 4-6 weeks
Other outcomes:
Locations:
city: Blegdamsvej 9
country: Denmark
facility: Psychiatric Department of Rigshospitalet
state: Copenhagen OE
Study officials:
affiliation: Psychiatric Department of Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen OE
name: Lars V Kessing, DMSc
role: STUDY_DIRECTOR
References:
citation: Knorr U, Vinberg M, Mortensen EL, Winkel P, Gluud C, Wetterslev J, Gether U, Kessing LV. Effect of chronic escitalopram versus placebo on personality traits in healthy first-degree relatives of patients with depression: a randomized trial. PLoS One. 2012;7(2):e31980. doi: 10.1371/journal.pone.0031980. Epub 2012 Feb 29.
citation: Knorr U, Vinberg M, Hansen A, Klose M, Feldt-Rasmussen U, Hilsted L, Hasselstrom J, Gether U, Winkel P, Gluud C, Wetterslev J, Kessing LV. Escitalopram and neuroendocrine response in healthy first-degree relatives to depressed patients--a randomized placebo-controlled trial. PLoS One. 2011;6(6):e21224. doi: 10.1371/journal.pone.0021224. Epub 2011 Jun 27.
citation: Knorr U, Vinberg M, Klose M, Feldt-Rasmussen U, Hilsted L, Gade A, Haastrup E, Paulson O, Wetterslev J, Gluud C, Gether U, Kessing L. Rationale and design of the participant, investigator, observer, and data-analyst-blinded randomized AGENDA trial on associations between gene-polymorphisms, endophenotypes for depression and antidepressive intervention: the effect of escitalopram versus placebo on the combined dexamethasone-corticotrophine releasing hormone test and other potential endophenotypes in healthy first-degree relatives of persons with depression. Trials. 2009 Aug 11;10:66. doi: 10.1186/1745-6215-10-66.