Prophylactic Effects of Agomelatine for Poststroke Depression

Study Overview
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Brief Summary
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The incidence of depression in stroke patients with frontal lobe involvement was reported to be as high as 42%. Agomelatin, a type 1/2 melatonin receptor agonist and serotonin 2C receptor antagonist, is effective in treatment of depression, but whether it can prevent poststroke depression (PSD) remains unknown. The PRAISED trial is a multicenter, randomized, double-blind trial and is designed to evaluate the efficacy and safety of agomelatine in the prevention of PSD in stroke patients with frontal lobe involvement. The primary outcome is the rate of post-stroke depression for 180 days.

Detailed Description
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This PRAISED trial is a multicenter, randomized, double-blind trial to evaluate the efficacy and safety of agomelatine in the prevention of PSD in patients with acute ischemic stroke. The sample size is 420. The participants will be randomized to receive a 6-month treatment of agomelatine 25mg/d or placebo 25mg/d. The primary end point is the proportion of PSD within 180 days. PSD is defined as the Hamilton Depression Rating Scale-17 (HAMD-17) ≥7 or diagnosis of depression by the Diagnostic and Statistical Manual of mental disorders-V (DSM-V). The second end point are rate of recurrence of ischemic stroke within 90 days, modified Rankin Scale (mRS), National Institutes of Health Stroke Scale (NIHSS), vascular death, transient ischemic attack (TIA)/stroke or myocardial infarction during the 6-months, cognitive function(Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA)), Pittsburgh Sleep Quality Index (PSQI), Fatigue Severity Scale (FSS), Epworth Sleepiness Scale (ESS), Stroke Specific Quality Of Life (SS-QOL) scale, adherence to medication, adverse events. The study consists of five visits including the day of randomization, day 14±3 days, day 28±3 days, day 90±7 days, day 180±7 days.

Official Title
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A Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Agomelatine in the Prevention of Poststroke Depression

Conditions
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Depression, Acute Ischemic Stroke

Intervention / Treatment
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* Drug: Agomelatine
* Drug: Placebo Tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: aged 18 75 years; within 7 days after stroke onset; CT or MRI showed lesions involving the frontal lobe; mRS≤2 before onset for recurrent ischemic stroke; HAMD-17<8 before enrollment; NIHSS<16; be consious and able to complete the relevant assessment scales. Exclusion Criteria: hemorrhagic stroke; with major depressive disorder, or have taken antidepressants within 30 days before stroke onset, or HAMD-17 ≥8; with other mental illnesses; history of drug abuse or alcohol dependence in the past 1 year with life-threatening illnesses or disorders which may affect the completion of the relevant assessment scale (e.g., hearing, language, visual impairment, etc.) with cognitive impairment who cannot complete the relevant assessment scale with serious neurodegeneration diseases (such as Parkinson's disease, Alzheimer's disease, etc.) infection or carriers of hepatitis B virus (HBV) or hepatitis C virus (HCV) serum ALT level ≥ 2 times of the upper limit of the reference interval or TBIL level > 1.5 times of the upper limit of the reference interval renal dysfunction (creatinine clearance < 90 ml/min/1.73 m2) allergic to or contra-indicated to agomelatine lactose intolerance pregnant or breast-feeding women withdraw from other clinical trials within 4 weeks or participating in other clinical trials unsuitable for inclusion considered by the investigators

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Agomelatine<br>The Agomelatine group will be received agomelatine (25 mg/day) for 180 days. | Drug: Agomelatine<br>* agomelatine 25 mg/day for 180 days<br>* Other names: Agomelatine Tablets;|
| Placebo Comparator: Placebo<br>The Placebo group will be received placebo (25 mg/day) for 180 days. | Drug: Placebo Tablets<br>* placebo 25 mg/day for 180 days<br>* Other names: Placebo Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| rate of PSD within 180 days | PSD is defined as Hamilton Depression Rating Scale-17 (HAMD-17) ≥7 or diagnosis of depression by DSM-V. | 180 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| rate of recurrence of ischemic stroke within 90 days | Acute onset of focal neurological deficit, a few can be comprehensive neurological deficit. 2. Brain CT/MRI confirms the corresponding infarct focus in the brain, or the symptoms and signs continue for more than 24h, or cause death within 24h. 3. Exclude non-ischemic causes. brain ct/mri confirmed the corresponding infarct focus in the brain, or the symptoms and signs continued for more than 24h, or caused death within 24h. exclude non ischemic causes. | 90±7 days | 
| variation of HAMD-17 score from baseline | range from 0 to 50; the higher, the worse | 14±3 days, 28±3 days, 90±7 days, and 180±7 days | 
| rate of sleep disorder | range from 0 to 21; > 7, having sleep disorder | 180 days | 
| variation of Pittsburgh Sleep Quality Index (PSQI) score from baseline | range from 0 to 21; the higher, the worse; > 7, having sleep disorder | 14±3 days, 28±3 days, 90±7 days and 180±7 days | 
| variation of Stroke Specific Quality of Life (SS-QOL) score from baseline | range from 50 to 248; the higher, the better | 28±3 days, 90±7 days, and 180±7 days | 
| variation of Modified Rankin Scale (mRS) score from baseline | range from 0 to 5; the higher, the worse | 28±3 days, 90±7 days and 180±7 days | 
| variation of National Institutes of Health Stroke Scale (NIHSS) from baseline | range from 0 to 42; the higher, the worse | 28±3 days, 90±7 days and 180±7 days | 
| variation of Montreal Cognitive Assessment (MOCA) from baseline | range from 0 to 30; the lower, the worse | 28±3 days, 90±7 days, and 180±7 days | 
| variation of Mini Mental State Examination (MMSE) score from baseline | range from 0 to 30; the lower, the worse | 28±3 days, 90±7 days, and 180±7 days | 
| variation of Epworth Sleepiness Scale (ESS) from baseline | range from 9 to 63; the higher, the worse | 28±3 days, 90±7 days, and 180±7 days | 
| rate of all-caused mortality | death due to all causes | 180 days | 
| variation of Fatigue Severity Scale (FSS) from baseline | range from 0 to 24; >=24, having drowsiness tendency | 28±3 days, 90±7 days, and 180±7 days | 
| rate of vascular events | defined as the composite of stroke, transient ischemic attack (TIA), myocardial infarction and vascular death | 180 days | 
| rate of liver injury | defend as the level of ALT 2 times higher than the upper limit of normal range | 28±3 days, 90±7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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poststroke depression, prevention, agomelatine