Prophylactic Effects of Agomelatine for Poststroke Depression

Depression Clinical Trial

— PRAISED  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05426304
• Other study ID #: PRAISED
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: October 1, 2022
• Est. completion date: May 31, 2024

Study information

• Verified date: July 2022
• Source: First Affiliated Hospital, Sun Yat-Sen University
• Contact: Jinsheng Zeng
• Phone: 13322800657
• Email: zengjs[@]pub.guangzhou.gd.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 420
• Est. completion date: May 31, 2024
• Est. primary completion date: May 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Ischemic Stroke
• Depression
• Depressive Disorder
• Ischemic Stroke

Intervention

Drug:
• Agomelatine
agomelatine 25 mg/day for 180 days
• Placebo Tablets
placebo 25 mg/day for 180 days

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
First Affiliated Hospital, Sun Yat-Sen University

References & Publications (17)

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Berg A, Palomäki H, Lehtihalmes M, Lönnqvist J, Kaste M. Poststroke depression: an 18-month follow-up. Stroke. 2003 Jan;34(1):138-43. — View Citation

Chern CM, Liao JF, Wang YH, Shen YC. Melatonin ameliorates neural function by promoting endogenous neurogenesis through the MT2 melatonin receptor in ischemic-stroke mice. Free Radic Biol Med. 2012 May 1;52(9):1634-47. doi: 10.1016/j.freeradbiomed.2012.01.030. Epub 2012 Feb 10. — View Citation

Chollet F, Tardy J, Albucher JF, Thalamas C, Berard E, Lamy C, Bejot Y, Deltour S, Jaillard A, Niclot P, Guillon B, Moulin T, Marque P, Pariente J, Arnaud C, Loubinoux I. Fluoxetine for motor recovery after acute ischaemic stroke (FLAME): a randomised placebo-controlled trial. Lancet Neurol. 2011 Feb;10(2):123-30. doi: 10.1016/S1474-4422(10)70314-8. Epub 2011 Jan 7. Erratum in: Lancet Neurol. 2011 Mar;10(3):205. — View Citation

Feng C, Fang M, Liu XY. The neurobiological pathogenesis of poststroke depression. ScientificWorldJournal. 2014 Mar 4;2014:521349. doi: 10.1155/2014/521349. eCollection 2014. Review. — View Citation

FOCUS Trial Collaboration. Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial. Lancet. 2019 Jan 19;393(10168):265-274. doi: 10.1016/S0140-6736(18)32823-X. Epub 2018 Dec 5. — View Citation

Gu J, Huang H, Chen K, Huang G, Huang Y, Xu H. Are they necessary? Preventive therapies for post-stroke depression: A meta-analysis of RCTs. Psychiatry Res. 2020 Feb;284:112670. doi: 10.1016/j.psychres.2019.112670. Epub 2019 Oct 31. Review. — View Citation

Hackett ML, Pickles K. Part I: frequency of depression after stroke: an updated systematic review and meta-analysis of observational studies. Int J Stroke. 2014 Dec;9(8):1017-25. doi: 10.1111/ijs.12357. Epub 2014 Aug 12. Review. — View Citation

Kim JS, Lee EJ, Chang DI, Park JH, Ahn SH, Cha JK, Heo JH, Sohn SI, Lee BC, Kim DE, Kim HY, Kim S, Kwon DY, Kim J, Seo WK, Lee J, Park SW, Koh SH, Kim JY, Choi-Kwon S; EMOTION investigators. Efficacy of early administration of escitalopram on depressive and emotional symptoms and neurological dysfunction after stroke: a multicentre, double-blind, randomised, placebo-controlled study. Lancet Psychiatry. 2017 Jan;4(1):33-41. doi: 10.1016/S2215-0366(16)30417-5. — View Citation

Niedermaier N, Bohrer E, Schulte K, Schlattmann P, Heuser I. Prevention and treatment of poststroke depression with mirtazapine in patients with acute stroke. J Clin Psychiatry. 2004 Dec;65(12):1619-23. — View Citation

Quera-Salva MA, Lemoine P, Guilleminault C. Impact of the novel antidepressant agomelatine on disturbed sleep-wake cycles in depressed patients. Hum Psychopharmacol. 2010 Apr;25(3):222-9. doi: 10.1002/hup.1112. Review. — View Citation

Robinson RG, Jorge RE, Moser DJ, Acion L, Solodkin A, Small SL, Fonzetti P, Hegel M, Arndt S. Escitalopram and problem-solving therapy for prevention of poststroke depression: a randomized controlled trial. JAMA. 2008 May 28;299(20):2391-400. doi: 10.1001/jama.299.20.2391. Erratum in: JAMA. 2009 Mar 11;301(10):1024. — View Citation

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Tsai CS, Wu CL, Chou SY, Tsang HY, Hung TH, Su JA. Prevention of poststroke depression with milnacipran in patients with acute ischemic stroke: a double-blind randomized placebo-controlled trial. Int Clin Psychopharmacol. 2011 Sep;26(5):263-7. doi: 10.1097/YIC.0b013e32834a5c64. — View Citation

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Zhao FY, Yue YY, Li L, Lang SY, Wang MW, Du XD, Deng YL, Wu AQ, Yuan YG. Clinical practice guidelines for post-stroke depression in China. Braz J Psychiatry. 2018 Jul-Sep;40(3):325-334. doi: 10.1590/1516-4446-2017-2343. Epub 2018 Feb 1. — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	rate of sleep disorder	range from 0 to 21; > 7, having sleep disorder	180 days
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	rate of all-caused mortality	death due to all causes	180 days
Secondary	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
Secondary	rate of vascular events	defined as the composite of stroke, transient ischemic attack (TIA), myocardial infarction and vascular death	180 days
Secondary	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