StrokePhase 3NCT01112813
The Neurotrophic Effects of Lithium Carbonate Following Stroke: A Feasibility Study
A Phase 3 study testing Lithium Carbonate in people with Stroke, run by Sunnybrook Health Sciences Centre at 1 site in Canada.
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. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Stroke
- What is being tested?
- Lithium Carbonate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteCanada
- Study dates
- Apr 2010to 25 Jul 2017
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- age >40 years
- male or female
- speaks and understands English
- within 12 months post-stroke
Who cannot join
- subarachnoid or intracranial hemorrhage
- severe aphasia or dysphasia
- impaired level of consciousness that would preclude neuropsychiatric testing
- significant acute medical illness that may contraindicate lithium treatment(including renal dysfunction; >106 umol/L creatinine level) affect neuropsychiatric assessments or serum BDNF results or put subject at risk from MRI procedure
- other psychiatric (exception of post-stroke depression) or neurological illnesses
- initiation of diuretic treatment
- use of antidepressant medications or initiation of antidepressant medications during the study
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the detailed 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.
- Conditions
- Stroke
- Being tested
- Lithium Carbonate
- Keywords
- Stroke, lithium, MRI, gray matter
- Medical subject headings
- Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lithium CarbonateDrug
Also called Carbolith
0.4-0.8 mmol/L for 2 months
| Study group | Role | What they receive |
|---|---|---|
| Lithium | Experimental | Lithium Carbonate, 0.4-0.8 mmol/L for 2 months Receives: Drug: Lithium Carbonate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Increase in total brain gray matter volumes
Measured: Baseline, 2 months
Secondary outcomes (3)
Cognitive tasks of the Neurological Disorders and Stroke - Canadian Stroke Network's (NINDS-CSN) 30 min. battery
Measured: Baseline, 2 months
Serum brain-derived neurotrophic factor (BDNF) levels
Measured: Baseline, 2 months
Serum lithium and creatinine levels
Measured: 1-week, 4-weeks, 8-weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Apr 2010 (estimated)
- Study startApr 2010
- Primary completion25 Jul 2017
- Study completion25 Jul 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for StrokeStudies of the same condition, open and under way.
- More trials run by Sunnybrook Health Sciences CentreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sunnybrook Health Sciences Centre
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Krista L Lanctôt, PhD, Principal investigator, Sunnybrook Health Sciences CentreNathan Herrmann, MD, Principal investigator, Sunnybrook Health Sciences Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01112813
- Sponsor's protocol ID
- Li-2010
- Status last verified
- Oct 2017
- First submitted
- 27 Apr 2010
- Last updated
- 31 Jan 2024
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Sun YR, Herrmann N, Scott CJM, Black SE, Swartz RH, Hopyan J, Lanctot KL. Lithium Carbonate in a Poststroke Population: Exploratory Analyses of Neuroanatomical and Cognitive Outcomes. J Clin Psychopharmacol. 2019 Jan/Feb;39(1):67-71. doi: 10.1097/JCP.0000000000000981.
PubMed 30566418
Study at a glance
From the registry record, last updated by the sponsor on 31 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Neurotrophic Effects of Lithium Carbonate Following Stroke: A Feasibility Study
- ClinicalTrials.gov ID
- NCT01112813
- Acronym / sponsor ID
- Li-2010
- Conditions
- Stroke
- Keywords
- Stroke, lithium, MRI, gray matter
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Sunnybrook Health Sciences CentreUniversity, hospital or other
- Study start
- Apr 2010
- Primary completion
- 25 Jul 2017 (actual)
- Study completion
- 25 Jul 2017 (actual)
- First posted
- 28 Apr 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Lithium | Experimental | Drug: Lithium CarbonateLithium Carbonate, 0.4-0.8 mmol/L for 2 months |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- age >40 years
- male or female
- speaks and understands English
- within 12 months post-stroke
Key exclusion criteria (7 listed)
- subarachnoid or intracranial hemorrhage
- severe aphasia or dysphasia
- impaired level of consciousness that would preclude neuropsychiatric testing
- significant acute medical illness that may contraindicate lithium treatment(including renal dysfunction; >106 umol/L creatinine level) affect neuropsychiatric assessments or serum BDNF results or put subject at risk from MRI procedure
- other psychiatric (exception of post-stroke depression) or neurological illnesses
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lithium CarbonateAlso: Carbolith0.4-0.8 mmol/L for 2 months | Drug | Lithium |
Primary outcome
Increase in total brain gray matter volumes
Time frame: Baseline, 2 months
3 secondary outcomes
Cognitive tasks of the Neurological Disorders and Stroke - Canadian Stroke Network's (NINDS-CSN) 30 min. battery
Time frame: Baseline, 2 months
Serum brain-derived neurotrophic factor (BDNF) levels
Time frame: Baseline, 2 months
Serum lithium and creatinine levels
Time frame: 1-week, 4-weeks, 8-weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jan 2024.
- Results publication: PubMed 30566418Sun YR, Herrmann N, Scott CJM, Black SE, Swartz RH, Hopyan J, Lanctot KL. Lithium Carbonate in a Poststroke Population: Exploratory Analyses of Neuroanatomical and Cognitive Outcomes. J Clin Psychopharmacol. 2019 Jan/Feb;39(1):67-71. doi: 10.1097/JCP.0000000000000981.
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Web-Based Tele-Rehabilitation Using Action Observation and Mirror Therapy for Subacute Stroke: A Randomized Controlled Trial
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Krista L Lanctôt, PhD principal investigator
Sunnybrook Health Sciences Centre
Nathan Herrmann, MD principal investigator
Sunnybrook Health Sciences Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Lithium Carbonate in people with Stroke, run by Sunnybrook Health Sciences Centre at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Increase in total brain gray matter volumes (time frame: Baseline, 2 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01112813, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jan 2024.