Stroke, IschemicNCT03725137
Post-stroke Immunological Changes in Young Stroke Patients
An observational study of Stroke, Ischemic and Cognitive Decline, run by University Medicine Greifswald.
Trial summary
In the present study, the investigators aim to elucidate the role of T-cells on cognitive decline in younger stroke patients, using repeated cognitive testing, brain imaging, and immunological analyses in the first 6 month after stroke. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Stroke, Ischemic, Cognitive Decline
- What is being tested?
- Analysis of T-lymphocytes
- How many people
- 77 participants
- Where
- No sites listed yet
- Study dates
- Jan 2020to Dec 2022
- Phase
- Observational
- 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 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Study population: Baseline visit: Patients will be recruited into the study within the first 72 hours after stroke onset. Only patients who are able to give their informed consent will be included in the study. Follow-up investigations: Follow-up investigations are scheduled for the 4th week post-stroke and after six months.
Who may be able to join
- Acute stroke that occurred within the last 72 hours as defined by acute neurological deficit in combination with an acute ischaemic infarct as documented by either a "Diffusion weighted imaging" (DWI)-positive lesion on MR imaging or a new lesion on a CT scan; only cortical/subcortical infarcts will be included
- Age > 18; ≤ 55
- Provision of written informed consent or through a surrogate as appropriate
- Willingness to participate in follow-up
- National Institute of Health Stroke Scale Score (NIHSS) ≥ 4
- German as first language (neuropsychological tests and cut-offs developed for native speakers)
Who cannot join
- Patients are excluded if they are not able to give informed consent due to severe cognitive deficits
- Signs of infection on admission (C-reactive protein ≥ 50 mg/L)
- Patients receiving immunosuppressive drugs or diagnosed with a malignancy or severe neurological diseases other than stroke (e.g., neurodegenerative movement disorders, motoneuron diseases)
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Role of Th1-lymphocytes in the Development of Vascular Cognitive Impairment in Young Stroke Patients
In the present study, the investigators aim to elucidate the role of T-cells on cognitive decline in younger stroke patients, using repeated cognitive testing, brain imaging, and immunological analyses in the first 6 month after stroke. The examiners will investigate (i) the extent and duration of stroke-induced changes in T cell function within the peripheral blood of patients; and (ii) post-stroke cognitive functions.
Read the detailed description
Demands from society on stroke patients of younger age are in most cases higher than for elderly stroke patients, because of occupational obligations and often their role as a caregiver for a young family. For example, return to their former workplace may be impossible even if cognitive deficits, e.g., in the memory domain, are only "minor" according to standardized tests. Thus, cognitive function after stroke is of utmost importance for activities of daily life and quality of life in young stroke patients. In order to prevent or at least reduce post-stroke cognitive decline, the mechanisms underlying the decline need to be further elucidated, to eventually develop new preventive and therapeutic approaches.
T-cell activation is associated with destruction of brain tissue. In neurodegenerative diseases that primarily impair cognitive functions, e. g., Alzheimers Disease, T-cells were identified as important mediators of disease pathology. Activation of cells of the adaptive immune system, most importantly T-cells, has been also investigated in experimental stroke. Here, these cells significantly contribute to secondary brain tissue damage. Stroke is associated with massive changes of the central and peripheral immune response. The investigators and other groups demonstrated that despite an overall lymphopenia, T-cells are functionally intact and pro-inflammatorily polarized, for at least two weeks post-stroke. Depletion of T cells has been shown to reduce infarct volume and to improve outcome in mice post-experimental stroke.
- Conditions
- Stroke, Ischemic, Cognitive Decline
- Being tested
- Analysis of T-lymphocytes
- Medical subject headings
- Ischemic Stroke, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Analysis of T-lymphocytesOther
Analysis of T-lymphocytes regarding the development of cognitive function after stroke
| Study group | Role | What they receive |
|---|---|---|
| Group A (young stroke) | Young stroke patients (≤ 55); Analysis of T-lymphocytes regarding: post-stroke t-cell priming (activation marker, polarization), cognitive tests; structural MRI Receives: Other: Analysis of T-lymphocytes |
What is being measured
The primary outcome is the main question the study is designed to answer.
Immune alterations, as determined via T-cell subtypes and function in comparison to cognitive outcome after stroke
The pro-inflammatorily primed T-cell response after stroke is associated with post-stroke cognitive decline, cognitive decline over time in young stroke patients
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2018
- Study startJan 2020 (estimated)
- Primary completionJan 2022 (estimated)
- Study completionDec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for Stroke, IschemicStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 77 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Medicine Greifswald
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Agnes Flöel, Prof.Dr.med., Study director, University Medicine Greifswald
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03725137
- Sponsor's protocol ID
- immuno_stroke
- Status last verified
- Nov 2019
- First submitted
- 29 Oct 2018
- Last updated
- 4 Dec 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Neau JP, Ingrand P, Mouille-Brachet C, Rosier MP, Couderq C, Alvarez A, Gil R. Functional recovery and social outcome after cerebral infarction in young adults. Cerebrovasc Dis. 1998 Sep-Oct;8(5):296-302. doi: 10.1159/000015869.
PubMed 9712928Waje-Andreassen U, Thomassen L, Jusufovic M, Power KN, Eide GE, Vedeler CA, Naess H. Ischaemic stroke at a young age is a serious event--final results of a population-based long-term follow-up in Western Norway. Eur J Neurol. 2013 May;20(5):818-23. doi: 10.1111/ene.12073. Epub 2013 Jan 7.
PubMed 23293975Babulal GM, Huskey TN, Roe CM, Goette SA, Connor LT. Cognitive impairments and mood disruptions negatively impact instrumental activities of daily living performance in the first three months after a first stroke. Top Stroke Rehabil. 2015 Apr;22(2):144-51. doi: 10.1179/1074935714Z.0000000012. Epub 2015 Mar 2.
PubMed 25936546Carod-Artal J, Egido JA, Gonzalez JL, Varela de Seijas E. Quality of life among stroke survivors evaluated 1 year after stroke: experience of a stroke unit. Stroke. 2000 Dec;31(12):2995-3000. doi: 10.1161/01.str.31.12.2995.
PubMed 11108762Hommel M, Miguel ST, Naegele B, Gonnet N, Jaillard A. Cognitive determinants of social functioning after a first ever mild to moderate stroke at vocational age. J Neurol Neurosurg Psychiatry. 2009 Aug;80(8):876-80. doi: 10.1136/jnnp.2008.169672. Epub 2009 Apr 8.
PubMed 19357128Nys GM, Van Zandvoort MJ, De Kort PL, Jansen BP, Van der Worp HB, Kappelle LJ, De Haan EH. Domain-specific cognitive recovery after first-ever stroke: a follow-up study of 111 cases. J Int Neuropsychol Soc. 2005 Nov;11(7):795-806. doi: 10.1017/s1355617705050952.
PubMed 16519259Spani C, Suter T, Derungs R, Ferretti MT, Welt T, Wirth F, Gericke C, Nitsch RM, Kulic L. Reduced beta-amyloid pathology in an APP transgenic mouse model of Alzheimer's disease lacking functional B and T cells. Acta Neuropathol Commun. 2015 Nov 11;3:71. doi: 10.1186/s40478-015-0251-x.
PubMed 26558367Dirnagl U, Klehmet J, Braun JS, Harms H, Meisel C, Ziemssen T, Prass K, Meisel A. Stroke-induced immunodepression: experimental evidence and clinical relevance. Stroke. 2007 Feb;38(2 Suppl):770-3. doi: 10.1161/01.STR.0000251441.89665.bc.
PubMed 17261736Meisel C, Schwab JM, Prass K, Meisel A, Dirnagl U. Central nervous system injury-induced immune deficiency syndrome. Nat Rev Neurosci. 2005 Oct;6(10):775-86. doi: 10.1038/nrn1765.
PubMed 16163382Prass K, Meisel C, Hoflich C, Braun J, Halle E, Wolf T, Ruscher K, Victorov IV, Priller J, Dirnagl U, Volk HD, Meisel A. Stroke-induced immunodeficiency promotes spontaneous bacterial infections and is mediated by sympathetic activation reversal by poststroke T helper cell type 1-like immunostimulation. J Exp Med. 2003 Sep 1;198(5):725-36. doi: 10.1084/jem.20021098. Epub 2003 Aug 25.
PubMed 12939340Vogelgesang A, May VE, Grunwald U, Bakkeboe M, Langner S, Wallaschofski H, Kessler C, Broker BM, Dressel A. Functional status of peripheral blood T-cells in ischemic stroke patients. PLoS One. 2010 Jan 14;5(1):e8718. doi: 10.1371/journal.pone.0008718.
PubMed 20090932Gorelick PB, Sacco RL. Stroke risk and prevention: introduction. Stroke. 2010 Oct;41(10 Suppl):S2. doi: 10.1161/STROKEAHA.110.598433. No abstract available.
PubMed 20876496Hurn PD, Subramanian S, Parker SM, Afentoulis ME, Kaler LJ, Vandenbark AA, Offner H. T- and B-cell-deficient mice with experimental stroke have reduced lesion size and inflammation. J Cereb Blood Flow Metab. 2007 Nov;27(11):1798-805. doi: 10.1038/sj.jcbfm.9600482. Epub 2007 Mar 28.
PubMed 17392692
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of Th1-lymphocytes in the Development of Vascular Cognitive Impairment in Young Stroke Patients
- ClinicalTrials.gov ID
- NCT03725137
- Acronym / sponsor ID
- immuno_stroke
- Conditions
- Stroke, Ischemic, Cognitive Decline
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 77 participants (estimated)
- Lead sponsor
- University Medicine GreifswaldUniversity, hospital or other
- Study start
- Jan 2020 (estimated)
- Primary completion
- Jan 2022 (estimated)
- Study completion
- Dec 2022 (estimated)
- First posted
- 30 Oct 2018 (actual)
- 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.
In the present study, the investigators aim to elucidate the role of T-cells on cognitive decline in younger stroke patients, using repeated cognitive testing, brain imaging, and immunological analyses in the first 6 month after stroke. The examiners will investigate (i) the extent and duration of stroke-induced changes in T cell function within the peripheral blood of patients; and (ii) post-stroke cognitive functions.
Detailed description
Demands from society on stroke patients of younger age are in most cases higher than for elderly stroke patients, because of occupational obligations and often their role as a caregiver for a young family. For example, return to their former workplace may be impossible even if cognitive deficits, e.g., in the memory domain, are only "minor" according to standardized tests. Thus, cognitive function after stroke is of utmost importance for activities of daily life and quality of life in young stroke patients. In order to prevent or at least reduce post-stroke cognitive decline, the mechanisms underlying the decline need to be further elucidated, to eventually develop new preventive and therapeutic approaches.
T-cell activation is associated with destruction of brain tissue. In neurodegenerative diseases that primarily impair cognitive functions, e. g., Alzheimers Disease, T-cells were identified as important mediators of disease pathology. Activation of cells of the adaptive immune system, most importantly T-cells, has been also investigated in experimental stroke. Here, these cells significantly contribute to secondary brain tissue damage. Stroke is associated with massive changes of the central and peripheral immune response. The investigators and other groups demonstrated that despite an overall lymphopenia, T-cells are functionally intact and pro-inflammatorily polarized, for at least two weeks post-stroke. Depletion of T cells has been shown to reduce infarct volume and to improve outcome in mice post-experimental stroke.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Group A (young stroke) | – | Other: Analysis of T-lymphocytesYoung stroke patients (≤ 55); Analysis of T-lymphocytes regarding: post-stroke t-cell priming (activation marker, polarization), cognitive tests; structural MRI |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- Baseline visit: Patients will be recruited into the study within the first 72 hours after stroke onset. Only patients who are able to give their informed consent will be included in the study. Follow-up investigations: Follow-up investigations are scheduled for the 4th week post-stroke and after six months.
Key inclusion criteria (6 listed)
- Acute stroke that occurred within the last 72 hours as defined by acute neurological deficit in combination with an acute ischaemic infarct as documented by either a "Diffusion weighted imaging" (DWI)-positive lesion on MR imaging or a new lesion on a CT scan; only cortical/subcortical infarcts will be included
- Age > 18; ≤ 55
- Provision of written informed consent or through a surrogate as appropriate
- Willingness to participate in follow-up
- National Institute of Health Stroke Scale Score (NIHSS) ≥ 4
Key exclusion criteria (3 listed)
- Patients are excluded if they are not able to give informed consent due to severe cognitive deficits
- Signs of infection on admission (C-reactive protein ≥ 50 mg/L)
- Patients receiving immunosuppressive drugs or diagnosed with a malignancy or severe neurological diseases other than stroke (e.g., neurodegenerative movement disorders, motoneuron diseases)
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 |
|---|---|---|
| Analysis of T-lymphocytesAnalysis of T-lymphocytes regarding the development of cognitive function after stroke | Other | Group A (young stroke) |
Primary outcome
Immune alterations, as determined via T-cell subtypes and function in comparison to cognitive outcome after stroke
Time frame: 3 years
The pro-inflammatorily primed T-cell response after stroke is associated with post-stroke cognitive decline, cognitive decline over time in young stroke patients
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2019.
- Background: PubMed 9712928Neau JP, Ingrand P, Mouille-Brachet C, Rosier MP, Couderq C, Alvarez A, Gil R. Functional recovery and social outcome after cerebral infarction in young adults. Cerebrovasc Dis. 1998 Sep-Oct;8(5):296-302. doi: 10.1159/000015869.
- Background: PubMed 23293975Waje-Andreassen U, Thomassen L, Jusufovic M, Power KN, Eide GE, Vedeler CA, Naess H. Ischaemic stroke at a young age is a serious event--final results of a population-based long-term follow-up in Western Norway. Eur J Neurol. 2013 May;20(5):818-23. doi: 10.1111/ene.12073. Epub 2013 Jan 7.
- Background: PubMed 25936546Babulal GM, Huskey TN, Roe CM, Goette SA, Connor LT. Cognitive impairments and mood disruptions negatively impact instrumental activities of daily living performance in the first three months after a first stroke. Top Stroke Rehabil. 2015 Apr;22(2):144-51. doi: 10.1179/1074935714Z.0000000012. Epub 2015 Mar 2.
- Background: PubMed 11108762Carod-Artal J, Egido JA, Gonzalez JL, Varela de Seijas E. Quality of life among stroke survivors evaluated 1 year after stroke: experience of a stroke unit. Stroke. 2000 Dec;31(12):2995-3000. doi: 10.1161/01.str.31.12.2995.
- Background: PubMed 19357128Hommel M, Miguel ST, Naegele B, Gonnet N, Jaillard A. Cognitive determinants of social functioning after a first ever mild to moderate stroke at vocational age. J Neurol Neurosurg Psychiatry. 2009 Aug;80(8):876-80. doi: 10.1136/jnnp.2008.169672. Epub 2009 Apr 8.
- Background: PubMed 16519259Nys GM, Van Zandvoort MJ, De Kort PL, Jansen BP, Van der Worp HB, Kappelle LJ, De Haan EH. Domain-specific cognitive recovery after first-ever stroke: a follow-up study of 111 cases. J Int Neuropsychol Soc. 2005 Nov;11(7):795-806. doi: 10.1017/s1355617705050952.
- Background: PubMed 26558367Spani C, Suter T, Derungs R, Ferretti MT, Welt T, Wirth F, Gericke C, Nitsch RM, Kulic L. Reduced beta-amyloid pathology in an APP transgenic mouse model of Alzheimer's disease lacking functional B and T cells. Acta Neuropathol Commun. 2015 Nov 11;3:71. doi: 10.1186/s40478-015-0251-x.
- Background: PubMed 17261736Dirnagl U, Klehmet J, Braun JS, Harms H, Meisel C, Ziemssen T, Prass K, Meisel A. Stroke-induced immunodepression: experimental evidence and clinical relevance. Stroke. 2007 Feb;38(2 Suppl):770-3. doi: 10.1161/01.STR.0000251441.89665.bc.
- Background: PubMed 16163382Meisel C, Schwab JM, Prass K, Meisel A, Dirnagl U. Central nervous system injury-induced immune deficiency syndrome. Nat Rev Neurosci. 2005 Oct;6(10):775-86. doi: 10.1038/nrn1765.
- Background: PubMed 12939340Prass K, Meisel C, Hoflich C, Braun J, Halle E, Wolf T, Ruscher K, Victorov IV, Priller J, Dirnagl U, Volk HD, Meisel A. Stroke-induced immunodeficiency promotes spontaneous bacterial infections and is mediated by sympathetic activation reversal by poststroke T helper cell type 1-like immunostimulation. J Exp Med. 2003 Sep 1;198(5):725-36. doi: 10.1084/jem.20021098. Epub 2003 Aug 25.
- Background: PubMed 20090932Vogelgesang A, May VE, Grunwald U, Bakkeboe M, Langner S, Wallaschofski H, Kessler C, Broker BM, Dressel A. Functional status of peripheral blood T-cells in ischemic stroke patients. PLoS One. 2010 Jan 14;5(1):e8718. doi: 10.1371/journal.pone.0008718.
- Background: PubMed 20876496Gorelick PB, Sacco RL. Stroke risk and prevention: introduction. Stroke. 2010 Oct;41(10 Suppl):S2. doi: 10.1161/STROKEAHA.110.598433. No abstract available.
- Individual participant dataSharing planned: No
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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.
Agnes Flöel, Prof.Dr.med. study director
University Medicine Greifswald
Questions about this trial
What is this clinical trial studying?
An observational study of Stroke, Ischemic and Cognitive Decline, run by University Medicine Greifswald.
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 6 inclusion and 3 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: status not confirmed, as of the sponsor's last update on 4 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
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.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Johanna Ruhnau, Dr.med. (+49 (0)3834 86-80482, johanna.ruhnau@uni-greifswald.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Immune alterations, as determined via T-cell subtypes and function in comparison to cognitive outcome after stroke (time frame: 3 years). 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 NCT03725137, which also lists 13 linked publications.
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 4 Dec 2019.