Precision Medicine in Stroke

Stroke Clinical Trial

— PROMISE  

Official title:

Precision Medicine in Stroke

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05815836
• Other study ID #: LMU_ISD_2023_PROMISE
• Status: Completed
• Start date: October 2013
• Est. completion date: December 2023

Study information

• Verified date: December 2023
• Source: Ludwig-Maximilians - University of Munich
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

PROMISE aims at identifying novel diagnostic and prognostic circulating biomarkers for patients with acute stroke and at informing on crucial yet undetected pathophysiological mechanisms driving outcome after stroke by enriching all phenotypic information available from clinical routine with in-depth quantification of the circulating proteome and metabolome as well as other entities.

Description:

The heterogeneity of ischemic stroke (IS) poses a challenge for assigning patients to optimal treatment strategies and is a major reason for the large number of failed clinical trials. Current diagnostic algorithms are insufficient to explain clinical outcomes arguing for crucial yet undetected pathophysiological mechanisms. Diagnostic tests further leave stroke etiology undetermined in 40 % of IS patients thus impeding the allocation of these patients to optimal secondary prevention regimens. Heterogeneity is also seen at the level of neuronal injury, which greatly varies between IS patients, but can neither be assessed in the pre-hospital setting nor serially in the acute phase to monitor stroke progression and to develop individual trajectories of neuronal loss over time. The circulating proteome and metabolome capture pathophysiological events from multiple organs including local and systemic events (e.g. stress) related to acute stroke and might thus inform on neuronal injury and the mechanisms causing stroke. The circulating proteome and metabolome may further inform on i) the systemic effects of stroke, which contribute significantly to stroke outcome but are under-researched, and ii) how concepts from preclinical stroke research such as reperfusion injury translate to human stroke. The investigators hypothesize that the combination of detailed clinical phenotyping with advanced profiling technologies (genomics, proteomics, and metabolomics) will enable the identification of key molecular signatures of IS that inform on pathophysiological mechanisms and might also be utilized as diagnostic instruments.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 787
• Est. completion date: December 2023
• Est. primary completion date: November 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients with acute ischemic stroke:
• Age 18 years or older
• Diagnosis of an acute ischemic stroke defined by an acute focal neurological deficit in combination with a diffusion-weighted imaging-positive lesion on magnetic resonance imaging or a new lesion on a delayed CT scan.
• Time from last seen well to admission and first blood sampling < 24 hours
• Blood samples collected upon admission (day 1), the next morning (day 2), day 3, and day 7 (or day of discharge if earlier)
• Informed consent in accord with ethical approval
• Patients with acute intracerebral hemorrhage:
• Age 18 years or older
• Diagnosis of an acute intracerebral hemorrhage defined by an acute focal neurological deficit in combination with imaging-based evidence of intracerebral hemorrhage.
• Time from last seen well to admission and first blood sampling < 24 hours
• Blood samples collected upon admission (day 1)
• Informed consent in accord with ethical approval
• Patients with stroke mimics:
• Age 18 years or older
• Diagnosis of a stroke-mimicking disease defined by an acute focal neurological deficit in combination with a lack of infarction on neuroimaging.
• Time from last seen well to admission and first blood sampling < 24 hours
• Blood samples collected upon admission (day 1), the next morning (day 2), day 3, and day 7
• Informed consent in accord with ethical approval
• Healthy subjects:
• Age 18 years or older
• Informed consent in accord with ethical approval

Exclusion Criteria:

• Patients with acute ischemic stroke:
• Lack of follow-up CT or MRI imaging
• Major surgery within the last four weeks
• In-house stroke
• Myocardial infarction, ischemic stroke, transient ischemic attacks, traumatic brain injury, cerebral venous sinus thrombosis, any intracranial hemorrhage, thrombosis, or pulmonary embolism within the last four weeks
• Chronic inflammatory bowel disease or percutaneous endoscopic gastrostomy
• Patients with acute intracerebral hemorrhage:
• Major surgery within the last four weeks
• In-house stroke
• Myocardial infarction, ischemic stroke, transient ischemic attacks, traumatic brain injury, cerebral venous sinus thrombosis, any intracranial hemorrhage, thrombosis, or pulmonary embolism within the last four weeks
• Chronic inflammatory bowel disease or percutaneous endoscopic gastrostomy
• Patients with stroke mimics:
• Major surgery within the last four weeks
• Myocardial infarction, ischemic stroke, transient ischemic attacks, traumatic brain injury, cerebral venous sinus thrombosis, any intracranial hemorrhage, thrombosis, or pulmonary embolism within the last four weeks
• Chronic inflammatory bowel disease or percutaneous endoscopic gastrostomy
• Healthy subjects:
• Major surgery within the last four weeks
• Myocardial infarction, ischemic stroke, transient ischemic attacks, traumatic brain injury, cerebral venous sinus thrombosis, any intracranial hemorrhage, thrombosis, or pulmonary embolism within the last four weeks
• Chronic inflammatory bowel disease or percutaneous endoscopic gastrostomy

Related Conditions & MeSH terms

• Brain Diseases
• Brain Ischemia
• Central Nervous System Diseases
• Cerebrovascular Disorders
• Ischemia
• Nervous System Diseases
• Stroke

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Ludwig-Maximilians - University of Munich

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Prediction of clinical outcome as defined by the modified Rankin Scale (mRS) score	The modified Rankin Scale (mRS) is a valid and reliable clinician-reported measure of global disability that has been widely applied for evaluating recovery from stroke. It is a scale used to measure functional recovery (the degree of disability or dependence in daily activities) of people who have suffered a stroke. mRS scores range from 0 (best outcome) to 6 (worst outcome), with 0 indicating no residual symptoms; 5 indicating bedbound, requiring constant care; and 6 indicating death. We will assess associations of clinical outcome with: Global, class, pathway, and individual metabolite levels upon admission (day 1), day 2, day 3, day7, and day 90 [raw values, referenced to HC, or referenced to SM]; Global, pathway, and individual protein levels upon admission (day 1), day 2, day 3, day7, and day 90 [raw values, referenced to HC, or referenced to SM]	3 months
Primary	Prediction of clinical outcome as defined by the modified Rankin Scale (mRS) score	The modified Rankin Scale (mRS) is a valid and reliable clinician-reported measure of global disability that has been widely applied for evaluating recovery from stroke. It is a scale used to measure functional recovery (the degree of disability or dependence in daily activities) of people who have suffered a stroke. mRS scores range from 0 (best outcome) to 6 (worst outcome), with 0 indicating no residual symptoms; 5 indicating bedbound, requiring constant care; and 6 indicating death. We will assess associations of clinical outcome with: Global, class, pathway, and individual metabolite levels upon admission (day 1), day 2, day 3, and day 7 [raw values, referenced to HC, or referenced to SM]; Global, pathway, and individual protein levels upon admission (day 1), day 2, day 3, and day 7 [raw values, referenced to HC, or referenced to SM]	7 days or day of discharge if earlier (on average 5 days)
Secondary	Acute brain injury as assessed by neuroimaging	The extent of acute brain injury (in ml) will be assessed on admission NCCT and CT perfusion scans.	day 1
Secondary	Subacute brain injury as assessed by neuroimaging	The extent of subacute brain injury will be manually segmented on images from delayed routine CT or MRI scans.	day 3 to day 10
Secondary	Neck and cerebral vessel morphology	We will assess the number of different plaque types on routine CT/MRI angiography scans.	day 1 to day 10
Secondary	Heart morphology and function as assessed by echocardiography and ECG	We will assess the likelihood of cardiac embolism by a score that integrates PTFV1, left ventricular strain and left atrial area.	day 1 to day 10
Secondary	Stroke etiology	Stroke etiology will be assessed using the TOAST classification systems.	7 days or day of discharge if earlier (on average 5 days)
Secondary	Sensitivity and specificity to separet diagnostic groups	Groups (Ischemic stroke, hemorrhagic stroke, stroke mimics, healthy subjects) will be compared.	day 1 to day 10
Secondary	Systemic sequelae of stroke	Systemic sequelae will be assessed by clinical laboratory tests.	day 1 to day 10
Secondary	Treatment efficacy of mechanical thrombectomy	Treatment efficacy will be assessed by comparing mRS scores between treated and non-treated groups.	day 1 to day 90