Clinical Trials Logo
NCT number NCT01112813
Study type Interventional
Source Sunnybrook Health Sciences Centre
Contact Janelle A Bradley, BSc
Phone 416-480-6100
Email jbradley@sri.utoronto.ca
Status Recruiting
Phase Phase 3
Start date April 2010
Completion date March 2018

Clinical Trial Summary

Stroke is the leading cause of adult disability and the third leading cause of death in Canada. Most stroke survivors live with residual impairments that diminish independence and quality of life. This may include vascular cognitive impairment (loss of ability to plan, think and reason) which can lead to dementia and loss of mental and functional independence.

The current treatment to reduce stroke induced brain tissue injury is limited to thrombolytics (clot busters), a therapy useful only if given in the first hours following stroke. One major new approach aims to reduce cell death after stroke by targeting the ongoing tissue loss initiated by the stroke. The tissue can be maintained by interfering with later neurochemical processes that are activated by stroke, potentially through activating natural substances in the brain that help survival and growth of nerve cells ("neurotrophic" factors).

The recent recognition of lithium as a neurotrophic agent has generated the first studies of lithium treatment for managing brain diseases. Clinically, lithium has now been shown to increase brain gray matter volume in bipolar patients. This effect is potentially important in stroke because gray matter loss has been implicated in the development of cognitive impairment after stroke, a result of the series of brain processes that are activated by lack of oxygen due to stroke. Our primary objective is to examine the effects of lithium on total brain gray matter volume in the post-stroke population, as measured by volumetric magnetic resonance imaging (MRI) with the hope that lithium may increase gray matter volume in post-stroke patients and lead to greater cognitive and functional rehabilitation. This study will provide valuable information on the tolerability of lithium, and its effects on clinical outcomes relevant to stroke, providing the information needed for designing a large-scale clinical trial.


Clinical Trial Description

The recognition of lithium as a neurotrophic agent has provided a rationale for evaluation of this agent in animal models of cerebral ischemia. Numerous animal and in vitro studies have shown lithium-mediated neurotrophic effects involve mechanisms highly relevant to the post-stroke population: the induction of brain-derived neurotrophic factor (BDNF) and inhibition of abnormal activity of glycogen synthase kinase 3 (GSK-3). Lithium has consistently been shown to increase serum concentration of the neurotrophic factor, BDNF. BDNF is involved with neuronal proliferation, survival, and differentiation and it facilitates cortical reorganization and functional recovery after focal ischemia (in rats). GSK-3 is a neurotrophic intermediary. In animal and in vitro models, lithium treatment effectively reduces the severity of ischemic damage and protects against ischemic damage of central nervous system (CNS) neurons resulting from glutamate-induced cell death. Importantly, these benefits were present when lithium was given after ischemic events rather than prophylactically.

The goal of pharmacotherapy post-stroke is to enhance restoration of neurological function and limit structural degradation. Gray matter atrophy is a relevant post-stroke relevant outcome as it has been implicated in the development of vascular cognitive impairment after stroke and is a result of the series of neurochemical processes that are activated by ischemia. While the first clinical studies examining the neurotrophic effects of lithium and its effects on total gray matter volume in bipolar subjects have just emerged, this has yet to be explored in the post-stroke population. Our primary objective is to determine the tolerability of lithium following a stroke and to examine its effects on clinical outcomes including total brain gray matter volume as measured by volumetric magnetic resonance imaging (MRI).

In this feasibility study, lithium carbonate (target 0.4 to 0.8 mmol/L) will be given open-label for 60 days, to consenting patients with unilateral ischemic cortical lesions. Total gray matter volume using magnetic resonance imaging will also be measured at baseline and termination, and related to changes in clinical outcomes (standardized scales measuring cognitive, activities of daily living, motor recovery) performed at the time of the MRIs. We expect to find that post-stroke patients receiving lithium will have increases in gray matter volume, and that increase in gray matter volume will predict improvements in clinical outcomes over 60 days. In addition, since lithium has been shown to increase serum concentration of the neurotrophic factor, BDNF, we will explore the relationship between plasma BDNF concentrations and neurological and clinical outcomes.

This study will provide key information of clinical importance that will determine whether a clinical trial with lithium is desirable and feasible. Results of this project have the potential to focus the development of lithium as a new treatment strategy that would improve outcomes at both the individual and societal level.


Study Design


Related Conditions & MeSH terms


See also
  Status Clinical Trial Phase
Completed NCT00391378 - Cerebral Lesions and Outcome After Cardiac Surgery (CLOCS) N/A
Completed NCT01662960 - Visual Feedback Therapy for Treating Individuals With Hemiparesis Following Stroke N/A
Recruiting NCT02822144 - General Anesthesia Versus Sedation During Intra-arterial Treatment for Stroke Phase 3
Recruiting NCT02513589 - Molecular Imaging of Inflammation With 18F-PBR06 to Identify Unstable Carotid Plaques in Patients With Stroke Phase 2
Not yet recruiting NCT03177954 - Developing a Patient Oriented Discharge Summary for Stroke Inpatients N/A
Recruiting NCT02917213 - Imaging Silent Brain Infarct And Thrombosis in Acute Myocardial Infarction N/A
Recruiting NCT02916030 - Vitamin D and Stroke N/A
Recruiting NCT03080454 - The Role of Trans-spinal Direct Current Stimulation (tsDCS) in Treating Patients With Hand Spasticity After Stroke N/A
Recruiting NCT02906956 - Music and Adherence Home Programs Post Stroke Phase 0
Recruiting NCT02960009 - Motor Excitability Study of High Definition Transcranial Direct Current Stimulation (HD-tDCS) in Chronic Stroke N/A
Recruiting NCT02889562 - Apixaban Versus Warfarin for the Management of Post-operative Atrial Fibrillation Phase 2/Phase 3
Recruiting NCT03183635 - Rapid Movement Therapy for Stroke Rehabilitation N/A
Recruiting NCT02828306 - Computer Based Algorithm for Patient Specific Implants for Cranioplasty in Patients With Skull Defects N/A
Active, not recruiting NCT02753257 - Validation of Sensitivity and Specificity of a Multi-Omic Precision Diagnostic for Acute Stroke Evaluation N/A
Enrolling by invitation NCT02898558 - Effect of Body Representation in Movement N/A
Completed NCT02868996 - An Open Label, Phase 1b, Ascending Dose Study of DM199 Phase 1
Completed NCT03053154 - Relationship Between Pelvic Tilt and Sit to Stand Task in Stroke Patients N/A
Completed NCT03025776 - One vs. Two Hand Use After Stroke: Role of Task Requirements Phase 0
Recruiting NCT02793934 - The Pilot Project Development Of MEdical Rehabilitation System in Russian Federation N/A
Recruiting NCT02360488 - Telerehabilitation in the Home Versus Therapy In-Clinic for Patients With Stroke Phase 1