Effect of Serotonin and Levodopa in Ischemic Stroke

Stroke Clinical Trial

— SELEIS  

Official title:

Effect of Serotonin and Levodopa Functional Recovery in Patients With Cerebral Infarction

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02386475
• Other study ID #: SELEIS
• Secondary ID: 2014-000846-32
• Status: Completed
• Phase: Phase 4
• Start date: January 2015
• Est. completion date: October 31, 2019

Study information

• Verified date: August 2017
• Source: Hospital de Granollers
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Cortical plasticity plays a pivotal role in functional recovery after a stroke. Neurotransmitter release, facilitates the creation of new synapses and promotes brain plasticity. In a pilot study, will evaluate the potential benefit of drugs that increase the release of neurotransmitters in patients with first stroke.

Description:

Methods. Evaluate 240 consecutive patients with a first ischemic stroke with NIHSS 5-20 without aphasia and with a previous independent functional status (mRS <3). Patients will be randomized into four arms: 1) control group, 2) treatment with citalopram 20 mg / day, 3) group levodopa (sinemet plus)100 mg / day, 4) group levodopa (sinemet plus) 100 mg / day + citalopram 20 mg / day.

The treatment begins within the first 5 days of stroke and is maintained for 6 months. All patients will be treated according to current guidelines for secondary prevention. We will assess the following variables: demographic, vascular risk factors, etiologic subtypes according to TOAST criteria, neurologic deficit with the NIHSS scale, cognitive assessment with Minimental scale and functional status with scale modified Rankin at discharge, 3, 6 and 12 months, Symbol Digit Modalities Test (SDMT), GDS-15 Geriatric Depression Scale, Logical memory of WMS-IV . The cognitive assessment and motor functional status will be evaluated by a neuropsychologist and neurologist blinded to treatment assignment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: October 31, 2019
• Est. primary completion date: March 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• • Patients with a first stroke with NIHSS 5-20 points

• Patients without aphasia to avoid interference in the assessment of depression and cognitive impairment

• Patients with independent functional status prior to stroke (mRS <3)

• Patients without prior cognitive impairment or depressive syndrome assessed by medical history with the patient and family.

• The assigned treatment initiated within the first five days of stroke

Exclusion Criteria:

• • Patients with prior myocardial or cerebral hemorrhage

• Patients with TIA

• Patients with aphasia

• History of cognitive impairment or prior depressive syndrome

• Patients with no independent functional status mRS greater than or equal to 3

• Underlying disease hopefully less than one year of life.

• Patient pre-treatment with levodopa, an antidepressant or neuroleptic.

Related Conditions & MeSH terms

• Stroke

Intervention

Other:
• placebo
In all cases, regardless of the assigned treatment group, will follow usual physiotherapy program and vascular risk factors, and treatment of stroke will be controlled according to current recommendations of the American Heart Association / American Stroke Association.

Drug:
• citalopram
In all cases, regardless of the assigned treatment group, will follow usual physiotherapy program and vascular risk factors, and treatment of stroke will be controlled according to current recommendations of the American Heart Association / American Stroke Association.
• sinemet plus
In all cases, regardless of the assigned treatment group, will follow usual physiotherapy program and vascular risk factors, and treatment of stroke will be controlled according to current recommendations of the American Heart Association / American Stroke Association.

Locations

Country	Name	City	State
Spain	Granollers General Hospital	Granollers	Barcelnoa

Sponsors (1)

Lead Sponsor	Collaborator
Hospital de Granollers

Country where clinical trial is conducted

Spain, 

References & Publications (26)

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Cooke EV, Mares K, Clark A, Tallis RC, Pomeroy VM. The effects of increased dose of exercise-based therapies to enhance motor recovery after stroke: a systematic review and meta-analysis. BMC Med. 2010 Oct 13;8:60. doi: 10.1186/1741-7015-8-60. Review. — View Citation

Costa RM. Plastic corticostriatal circuits for action learning: what's dopamine got to do with it? Ann N Y Acad Sci. 2007 May;1104:172-91. Epub 2007 Apr 13. Review. — View Citation

Dam M, Tonin P, De Boni A, Pizzolato G, Casson S, Ermani M, Freo U, Piron L, Battistin L. Effects of fluoxetine and maprotiline on functional recovery in poststroke hemiplegic patients undergoing rehabilitation therapy. Stroke. 1996 Jul;27(7):1211-4. — View Citation

Gladstone DJ, Danells CJ, Armesto A, McIlroy WE, Staines WR, Graham SJ, Herrmann N, Szalai JP, Black SE; Subacute Therapy with Amphetamine and Rehabilitation for Stroke Study Investigators. Physiotherapy coupled with dextroamphetamine for rehabilitation after hemiparetic stroke: a randomized, double-blind, placebo-controlled trial. Stroke. 2006 Jan;37(1):179-85. Epub 2005 Dec 1. — View Citation

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Lim CM, Kim SW, Park JY, Kim C, Yoon SH, Lee JK. Fluoxetine affords robust neuroprotection in the postischemic brain via its anti-inflammatory effect. J Neurosci Res. 2009 Mar;87(4):1037-45. doi: 10.1002/jnr.21899. — View Citation

Martinsson L, Hårdemark H, Eksborg S. Amphetamines for improving recovery after stroke. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD002090. Review. — View Citation

Pariente J, Loubinoux I, Carel C, Albucher JF, Leger A, Manelfe C, Rascol O, Chollet F. Fluoxetine modulates motor performance and cerebral activation of patients recovering from stroke. Ann Neurol. 2001 Dec;50(6):718-29. — View Citation

Petty GW, Brown RD Jr, Whisnant JP, Sicks JD, O'Fallon WM, Wiebers DO. Ischemic stroke subtypes : a population-based study of functional outcome, survival, and recurrence. Stroke. 2000 May;31(5):1062-8. — View Citation

Platz T, Kim IH, Engel U, Pinkowski C, Eickhof C, Kutzner M. Amphetamine fails to facilitate motor performance and to enhance motor recovery among stroke patients with mild arm paresis: interim analysis and termination of a double blind, randomised, placebo-controlled trial. Restor Neurol Neurosci. 2005;23(5-6):271-80. — View Citation

Robinson RG, Schultz SK, Castillo C, Kopel T, Kosier JT, Newman RM, Curdue K, Petracca G, Starkstein SE. Nortriptyline versus fluoxetine in the treatment of depression and in short-term recovery after stroke: a placebo-controlled, double-blind study. Am J Psychiatry. 2000 Mar;157(3):351-9. — View Citation

Ruscher K, Kuric E, Wieloch T. Levodopa treatment improves functional recovery after experimental stroke. Stroke. 2012 Feb;43(2):507-13. doi: 10.1161/STROKEAHA.111.638767. Epub 2011 Nov 17. — View Citation

Saxena SK, Ng TP, Koh G, Yong D, Fong NP. Is improvement in impaired cognition and depressive symptoms in post-stroke patients associated with recovery in activities of daily living? Acta Neurol Scand. 2007 May;115(5):339-46. — View Citation

Sonde L, Lökk J. Effects of amphetamine and/or L-dopa and physiotherapy after stroke - a blinded randomized study. Acta Neurol Scand. 2007 Jan;115(1):55-9. — View Citation

Sun Y, Jin K, Xie L, Childs J, Mao XO, Logvinova A, Greenberg DA. VEGF-induced neuroprotection, neurogenesis, and angiogenesis after focal cerebral ischemia. J Clin Invest. 2003 Jun;111(12):1843-51. — View Citation

Thrift AG, Dewey HM, Macdonell RA, McNeil JJ, Donnan GA. Stroke incidence on the east coast of Australia: the North East Melbourne Stroke Incidence Study (NEMESIS). Stroke. 2000 Sep;31(9):2087-92. — View Citation

Treig T, Werner C, Sachse M, Hesse S. No benefit from D-amphetamine when added to physiotherapy after stroke: a randomized, placebo-controlled study. Clin Rehabil. 2003 Sep;17(6):590-9. — View Citation

Yamashita T, Ninomiya M, Hernández Acosta P, García-Verdugo JM, Sunabori T, Sakaguchi M, Adachi K, Kojima T, Hirota Y, Kawase T, Araki N, Abe K, Okano H, Sawamoto K. Subventricular zone-derived neuroblasts migrate and differentiate into mature neurons in the post-stroke adult striatum. J Neurosci. 2006 Jun 14;26(24):6627-36. — View Citation

Yan T, Hui-Chan CW, Li LS. Functional electrical stimulation improves motor recovery of the lower extremity and walking ability of subjects with first acute stroke: a randomized placebo-controlled trial. Stroke. 2005 Jan;36(1):80-5. Epub 2004 Nov 29. — View Citation

* Note: There are 26 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rankin Scale		12 months