The Efficacy of Citalopram Treatment in Acute Stroke

Stroke, Ischemic Clinical Trial

— TALOS  

Official title:

The Efficacy of Citalopram Treatment in Acute Stroke

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01937182
• Other study ID #: 2013-002253-30
• Status: Completed
• Phase: Phase 2
• First received: September 3, 2013
• Last updated: February 23, 2017
• Start date: September 2013
• Est. completion date: December 19, 2016

Study information

• Verified date: December 2016
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

We wish to conduct a prospective, randomized, double blind, placebo controlled multi center study of the combined neuroprotective and antithrombotic effects of SSRI treatment after stroke.

Hypotheses:

SSRI treatment commenced in the acute phase of stroke (day 0-7) protects against new thromboembolic events and leads to better rehabilitation. 600 stroke patients will be randomized in a 1:1 ratio.

The treatment and follow up period is 6 months. During these 6 months there will be 2 clinical follow up visits, one telephone control and one visit to evaluate compliance regarding medication.

Description:

Design TALOS is an investigator-initiated, national multicenter randomized- and placebo-controlled, double blind trial testing citalopram in acute ischemic stroke.

Randomization Eligible patients will be randomized 1:1 to treatment with either citalopram or placebo. Treatment allocation is double-blinded based on computer-generated algorithm via a dedicated website. Patients whose treatment is stopped within 31 days after inclusion will be replaced.

Intervention and follow-up Patients randomized to citalopram will receive oral treatment with 20 mg tablets (10 mg if age ≥65 and/or reduced liver function) for 6 months with telephone contact after 2 weeks and 3 months and follow-up visits at 1 and 6 months. If patients develop depression dosage is initially doubled, followed by an additional control to evaluate effect and, if necessary, shifted to open-label antidepressant treatment. After 6 months, treatment will either stop or switch to open-label antidepressants at the discretion of the investigator.

Substudy 120 of patients will begin treatment within 12 hours after treatment with recombinant tissue plasminogen activator. These patients will receive a standard acute magnetic resonance imaging (MRI) with additional perfusion and angio sequences. The 24-hour control scan will be done using MRI instead of conventional CT.

Data monitoring When 300 patients have been included in the trial, an interim analysis will be performed. The unblinded results of this analysis will be reviewed by an independent data monitoring committee.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 642
• Est. completion date: December 19, 2016
• Est. primary completion date: December 19, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• First ever ischemic stroke

• Age 18 years or above

Exclusion Criteria:

• Hemorrhagic stroke

• Dementia or other neurodegenerative disease

• Antidepressant medical treatment within 6 months of admission

• Acute need for antidepressant treatment

• Drug abuse or other conditions that may indicate noncompliant behavior

• Liver failure (increased liver enzyme levels up to or more than 2 times upper limit)

• Renal failure (eGFR below 30 ml/min per 1.73m2)

• Hyponatremia (S-potassium below 130 mmol/l)

• Actively bleeding ulcer

• Fatal stroke or other severe co-morbidity that markedly decreases expected life span

• Prolonged corrected QT-interval (QTc above 480 ms)

• Ongoing treatment with drugs known to prolong the QTc interval

Related Conditions & MeSH terms

• Stroke
• Stroke, Ischemic

Intervention

Drug:
• Citalopram
Citalopram 10-40 mg per day administered orally
• Placebo
1/2-2 tablets per day with no intrinsic drug activity

Locations

Country	Name	City	State
Denmark	Aalborg University Hospital, Department of Neurology	Aalborg
Denmark	Aarhus University Hospital, Department of Neurology	Aarhus
Denmark	Glostrup University Hospital, Department of Neurology	Glostrup

Sponsors (3)

Lead Sponsor	Collaborator
University of Aarhus	Danish Council for Independent Research, The Danish Regions Medicine Foundation

Country where clinical trial is conducted

Denmark, 

References & Publications (4)

Adelborg K, Sundbøll J, Videbech P, Grove EL. The Risk of Thromboembolism in Users of Antidepressants and Antipsychotics. Adv Exp Med Biol. 2017;906:351-361. — View Citation

Bonaventura A, Liberale L, Vecchié A, Casula M, Carbone F, Dallegri F, Montecucco F. Update on Inflammatory Biomarkers and Treatments in Ischemic Stroke. Int J Mol Sci. 2016 Nov 25;17(12). pii: E1967. Review. — View Citation

Mortensen JK, Johnsen SP, Larsson H, Andersen G. Early Antidepressant Treatment and All-Cause 30-Day Mortality in Patients with Ischemic Stroke. Cerebrovasc Dis. 2015;40(1-2):81-90. doi: 10.1159/000435819. — View Citation

Siepmann T, Penzlin AI, Kepplinger J, Illigens BM, Weidner K, Reichmann H, Barlinn K. Selective serotonin reuptake inhibitors to improve outcome in acute ischemic stroke: possible mechanisms and clinical evidence. Brain Behav. 2015 Sep 23;5(10):e00373. doi: 10.1002/brb3.373. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Vascular death, Transient Ischemic Attack (TIA)/stroke and myocardial infarction (combined)	Myocardial Infarction: STEMI (ST segment elevation myocardial infarction) and NSTEMI (non-ST segment elevation myocardial infarction)	6 months
Primary	Functional status at 6-months	Functional status at 6-months, measured by the modified Rankin Scale	6 months
Secondary	Vascular death		6 months
Secondary	Death of any cause		6 months
Secondary	TIA/stroke		6 months
Secondary	Bleeding	Using the Global Utilization Of Streptokinase And Tpa For Occluded Arteries definition for bleeding (GUSTO)	6 months
Secondary	Myocardial infarction	STEMI (ST segment elevation myocardial infarction) and NSTEMI (non-ST segment elevation myocardial infarction)	6 months
Secondary	Disability/dependence	Using the modified Rankin Scale and the Barthel Index (BI)	6 months
Secondary	Physical activity	Using the Physical Activity Scale for the Elderly (PASE)	6 months
Secondary	Cognitive and organic cerebral impairment	Using the Mini-Mental State Examination and the Symbol Digit Modalities Test	6 months
Secondary	Fatigue	Using the Multidimensional Fatigue Inventory	6 months
Secondary	Post-stroke depression	Using the Major Depression Inventory test (MDI), Global depression scale (self and clinician and Hamilton Depression Scale - 6 item (HAM-D6)	6 months
Secondary	Pathological Crying	Using the Pathological Crying Scale	6 months
Secondary	Lesion size	Using FLAIR positive lesion size on MRI 24 hours after treatment with Alteplase	6 months

External Links

•   Danish Stroke Center
•   LinkedIn
•   Researchgate
•   Strokecenter.org