Prophylactic Effects of Agomelatine for Poststroke Depression

Phase 4

• Conditions: Acute Ischemic Stroke; Depression
• Interventions: Drug: Placebo Tablets; Drug: Agomelatine

• Registration Number: NCT05426304
• Lead Sponsor: First Affiliated Hospital, Sun Yat-Sen University

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2022-05-02
• Study First Submitted QC: 2022-06-16
• Study First Posted: 2022-06-21
• Status Verified: 2022-07
• Last Update Submitted: 2022-07-26
• Last Update Posted: 2022-07-27
• Study Start: 2022-10-01
• Primary Completion: 2024-05-31
• Study Completion: 2024-05-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 420

Inclusion Criteria

1. aged 18~75 years;
2. within 7 days after stroke onset;
3. CT or MRI showed lesions involving the frontal lobe;
4. mRS≤2 before onset for recurrent ischemic stroke;
5. HAMD-17<8 before enrollment;
6. NIHSS<16;
7. be consious and able to complete the relevant assessment scales.

Exclusion Criteria

1. hemorrhagic stroke;
2. with major depressive disorder, or have taken antidepressants within 30 days before stroke onset, or HAMD-17 ≥8;
3. with other mental illnesses;
4. history of drug abuse or alcohol dependence in the past 1 year
5. with life-threatening illnesses or disorders which may affect the completion of the relevant assessment scale (e.g., hearing, language, visual impairment, etc.)
6. with cognitive impairment who cannot complete the relevant assessment scale
7. with serious neurodegeneration diseases (such as Parkinson's disease, Alzheimer's disease, etc.)
8. infection or carriers of hepatitis B virus (HBV) or hepatitis C virus (HCV)
9. 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
10. renal dysfunction (creatinine clearance < 90 ml/min/1.73 m2)
11. allergic to or contra-indicated to agomelatine
12. lactose intolerance
13. pregnant or breast-feeding women
14. withdraw from other clinical trials within 4 weeks or participating in other clinical trials
15. unsuitable for inclusion considered by the investigators

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo Tablets	The Placebo group will be received placebo (25 mg/day) for 180 days.
Agomelatine	Agomelatine	The Agomelatine group will be received agomelatine (25 mg/day) for 180 days.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
variation of HAMD-17 score from baseline	14±3 days, 28±3 days, 90±7 days, and 180±7 days	range from 0 to 50; the higher, the worse
rate of recurrence of ischemic stroke within 90 days	90±7 days	1. 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.; 2. 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.; 3. exclude non ischemic causes.
variation of Pittsburgh Sleep Quality Index (PSQI) score from baseline	14±3 days, 28±3 days, 90±7 days and 180±7 days	range from 0 to 21; the higher, the worse; \> 7, having sleep disorder
variation of Epworth Sleepiness Scale (ESS) from baseline	28±3 days, 90±7 days, and 180±7 days	range from 9 to 63; the higher, the worse
variation of National Institutes of Health Stroke Scale (NIHSS) from baseline	28±3 days, 90±7 days and 180±7 days	range from 0 to 42; the higher, the worse
rate of vascular events	180 days	defined as the composite of stroke, transient ischemic attack (TIA), myocardial infarction and vascular death
rate of sleep disorder	180 days	range from 0 to 21; \> 7, having sleep disorder
variation of Stroke Specific Quality of Life (SS-QOL) score from baseline	28±3 days, 90±7 days, and 180±7 days	range from 50 to 248; the higher, the better
rate of all-caused mortality	180 days	death due to all causes
rate of liver injury	28±3 days, 90±7 days	defend as the level of ALT 2 times higher than the upper limit of normal range
variation of Montreal Cognitive Assessment (MOCA) from baseline	28±3 days, 90±7 days, and 180±7 days	range from 0 to 30; the lower, the worse
variation of Fatigue Severity Scale (FSS) from baseline	28±3 days, 90±7 days, and 180±7 days	range from 0 to 24; \>=24, having drowsiness tendency
variation of Modified Rankin Scale (mRS) score from baseline	28±3 days, 90±7 days and 180±7 days	range from 0 to 5; the higher, the worse
variation of Mini Mental State Examination (MMSE) score from baseline	28±3 days, 90±7 days, and 180±7 days	range from 0 to 30; the lower, the worse