Prophylactic Effects of Agomelatine for Poststroke Depression

NCT ID: NCT05426304

Last Updated: 2022-07-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

420 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-10-01

Study Completion Date

2024-05-31

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.

Conditions

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Depression Acute Ischemic Stroke

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Agomelatine

The Agomelatine group will be received agomelatine (25 mg/day) for 180 days.

Group Type EXPERIMENTAL

Agomelatine

Intervention Type DRUG

agomelatine 25 mg/day for 180 days

Placebo

The Placebo group will be received placebo (25 mg/day) for 180 days.

Group Type PLACEBO_COMPARATOR

Placebo Tablets

Intervention Type DRUG

placebo 25 mg/day for 180 days

Interventions

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Agomelatine

agomelatine 25 mg/day for 180 days

Intervention Type DRUG

Placebo Tablets

placebo 25 mg/day for 180 days

Intervention Type DRUG

Other Intervention Names

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Agomelatine Tablets Placebo Placebo

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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First Affiliated Hospital, Sun Yat-Sen University

OTHER

Sponsor Role lead

Responsible Party

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Jinsheng Zeng, MD, PhD

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Jinsheng Zeng

Role: STUDY_CHAIR

First Affiliated Hospital, Sun Yat-Sen University

Central Contacts

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Jinsheng Zeng

Role: CONTACT

13322800657

References

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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.

Reference Type BACKGROUND
PMID: 29412338 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25117911 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26684921 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29128343 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24744682 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31740211 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28012485 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30528472 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17303771 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18505948 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16889454 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21216670 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21811172 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15641866 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12511765 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20373473 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22330064 (View on PubMed)

Other Identifiers

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PRAISED

Identifier Type: -

Identifier Source: org_study_id

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