Clinical trial NCT05426304: Prophylactic Effects of Agomelatine for Poststroke Depression
Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Agomelatine in the Prevention of Poststroke Depression
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Depression
Acute Ischemic Stroke
Keywords: poststroke depression, prevention, agomelatine
Lead sponsor: First Affiliated Hospital, Sun Yat-Sen University
Sponsor class: OTHER
First posted: 2022-06-21
Enrollment: 420
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: rate of PSD within 180 days
timeFrame: 180 days
Secondary outcomes:
measure: rate of recurrence of ischemic stroke within 90 days
timeFrame: 90±7 days
measure: variation of HAMD-17 score from baseline
timeFrame: 14±3 days, 28±3 days, 90±7 days, and 180±7 days
measure: rate of sleep disorder
timeFrame: 180 days
measure: variation of Pittsburgh Sleep Quality Index (PSQI) score from baseline
timeFrame: 14±3 days, 28±3 days, 90±7 days and 180±7 days
measure: variation of Stroke Specific Quality of Life (SS-QOL) score from baseline
timeFrame: 28±3 days, 90±7 days, and 180±7 days
measure: variation of Modified Rankin Scale (mRS) score from baseline
timeFrame: 28±3 days, 90±7 days and 180±7 days
measure: variation of National Institutes of Health Stroke Scale (NIHSS) from baseline
timeFrame: 28±3 days, 90±7 days and 180±7 days
measure: variation of Montreal Cognitive Assessment (MOCA) from baseline
timeFrame: 28±3 days, 90±7 days, and 180±7 days
measure: variation of Mini Mental State Examination (MMSE) score from baseline
timeFrame: 28±3 days, 90±7 days, and 180±7 days
measure: variation of Epworth Sleepiness Scale (ESS) from baseline
timeFrame: 28±3 days, 90±7 days, and 180±7 days
measure: rate of all-caused mortality
timeFrame: 180 days
measure: variation of Fatigue Severity Scale (FSS) from baseline
timeFrame: 28±3 days, 90±7 days, and 180±7 days
measure: rate of vascular events
timeFrame: 180 days
measure: rate of liver injury
timeFrame: 28±3 days, 90±7 days
Other outcomes:
Locations:
Study officials:
affiliation: First Affiliated Hospital, Sun Yat-Sen University
name: Jinsheng Zeng
role: STUDY_CHAIR
References:
citation: 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.
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.
citation: Robinson RG, Jorge RE. Post-Stroke Depression: A Review. Am J Psychiatry. 2016 Mar 1;173(3):221-31. doi: 10.1176/appi.ajp.2015.15030363. Epub 2015 Dec 18.
citation: Villa RF, Ferrari F, Moretti A. Post-stroke depression: Mechanisms and pharmacological treatment. Pharmacol Ther. 2018 Apr;184:131-144. doi: 10.1016/j.pharmthera.2017.11.005. Epub 2017 Nov 9.
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.
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.
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.
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.
citation: Williams LS, Kroenke K, Bakas T, Plue LD, Brizendine E, Tu W, Hendrie H. Care management of poststroke depression: a randomized, controlled trial. Stroke. 2007 Mar;38(3):998-1003. doi: 10.1161/01.STR.0000257319.14023.61. Epub 2007 Feb 15.
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.
citation: Almeida OP, Waterreus A, Hankey GJ. Preventing depression after stroke: Results from a randomized placebo-controlled trial. J Clin Psychiatry. 2006 Jul;67(7):1104-9. doi: 10.4088/jcp.v67n0713.
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.
citation: 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.
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. doi: 10.4088/jcp.v65n1206.
citation: Berg A, Palomaki H, Lehtihalmes M, Lonnqvist J, Kaste M. Poststroke depression: an 18-month follow-up. Stroke. 2003 Jan;34(1):138-43. doi: 10.1161/01.str.0000048149.84268.07.
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.
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.