Prediction of Delayed Cerebral Ischemia After Subarachnoid Hemorrhage Using Dynamic 18F-FDG PET/CT (PREDISP)

Prediction and Unraveling of Delayed Cerebral Ischemia in Patients With Subarachnoid Hemorrhage Using Early Dynamic 18F-FDG PET/CT Assessment of Cerebral Glucose Uptake (PREDISP)

A pilot trial for assessing early microvascular alterations after aneurysmal subarachnoid hemorrhage using dynamic 18F-FDG PET/CT. The primary endpoint will be the measure of early changes in cerebral glucose uptake reflecting microperfusion.

Study Overview

• Status: Recruiting
• Conditions: Aneurysmal Subarachnoid Haemorrhage
• Intervention / Treatment: Other: Early dynamic 18F-FDG PET/CT assessment of cerebral glucose uptake

Detailed Description

We hypothesize that an early irreversible microvascular deterioration following initial bleeding could contribute to DCI occurrence. More precisely, we suspect that DCI areas are somehow overlaps of regions in which microperfusion is precociously altered, shortening circulatory reserves, and territories of secondarily spasmed arteries further lowering blood flow, resulting in ischemia. We aim to explore the potential microvasculature alteration through cerebral glucose perfusion and metabolism assessment using early dynamic 18F-fluorodesoxyglucose Positron Emission Tomography/Computer Tomography (dynamic 18F-FDG PET/CT). If our hypothesis turned out to be valid, we would at the same time be able to determine risk factors for this unpredictable complication and gain remarkable insight into DCI pathophysiology. Thus, the purpose of this trial is to demonstrate, in patients affected by SAH, the correlation between early cerebral glucose uptake defects in 18F-FDG PET/CT and delayed cerebral infarction in magnetic resonance imaging (MRI).

• Study Type: Interventional
• Enrollment (Anticipated): 35
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kevin CHALARD, M.D.; Phone Number: +33 788 014 588; Email: k-chalard@chu-montpellier.fr
• Study Contact Backup: Name: Pierre-Francois PERRIGAULT, M.D.; Email: pf-perrigault@chu-montpellier.fr

Study Locations

• France
  • Montpellier, France, 34295
    • Recruiting
    • Département d'Anesthésie-Réanimation Gui de Chauliac 80 Av Augustin.Fliche
    • Contact: Oceane GARNIER, CRA; Phone Number: 04 67 33 91 68; Email: o-garnier@chu-montpellier.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• written informed consent to participate in the study must be obtained from the subject or proxy/legal representative prior to enrollment.
• males and females aged 18 years and older.
• SAH proven by computed tomography (CT) and that has occurred within the last 72 hours.
• ruptured saccular aneurysm angiographically confirmed by digital subtraction angiogram or CT angiogram, which has been successfully secured by surgical clipping or endovascular coiling.
• high-risk subjects for DCI: "thick clot" on the hospital admission CT (grade 3 or grade 4 on the modified Fisher Scale).
• a woman of childbearing potential is eligible only if the serum pregnancy test performed during the screening period is negative.

Exclusion Criteria:

• PET/CT contradications
• MRI contradications
• gadolinium or meglumine hypersensitivity
• glomerular filtration rate <30mL/min
• SAH due to other causes than ruptured saccular aneurysm.
• post-HSA cardiac arrest.
• high sustained ICP ( >20mmHg lasting >20min) despite optimal treatment.
• significant and concomitant organ failure amongst the following: hypotension with systolic blood pressure <90mmHg refractory to treatment; unresolved pulmonary edema or pneumonia with severe hypoxia defined as PaO2/FiO2 <150; severe cardiac failure requiring inotropic support.
• patients with "do-not-resuscitate" orders, withdrawal of care situation, dying patient.
• vulnerable patient populations (minor, legal vulnerability, prisoner)
• pregnant and nursing mothers.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Intervention Group; All participants will receive study intervention

Other: Early dynamic 18F-FDG PET/CT assessment of cerebral glucose uptake; The intervention will consist in a dynamic cerebral 18F-FDG PET study performed at D2+/-1. Kinetic modeling will be performed using in-house software at the global, regional, and voxel level. In addition, cerebral perfusion and blood-brain-barrier permeability will be assessed at D4+/- 1 using perfusion MRI and permeability MRI.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantification of K1 parameter.	A kinetic modeling for cerebral glucose uptake will be performed using in-house software in order to provide the K1 parameter (in min-1) in every voxel reflecting the cerebral blood flow (in mL/min).	Day 2 +/- 1 day after the initial bleeding
Quantification of Ki parameter.	A kinetic modeling for cerebral glucose uptake will be performed using in-house software in order to provide the Ki parameter (in min-1) in every voxel reflecting the cerebral metabolic rate of glucose in µmol/100g/min.	Day 2 +/- 1 day after the initial bleeding

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Delayed cerebral ischemic regions.	Delayed cerebral ischemic lesions will be ascertained by routine MRI scans until the end of the period of time in which the subject may present DCI (D21+/-3).	From day 2 to day 21 +/- 3 days after the initial bleeding
Delayed spasmed arteries territories.	Occurence of vasospasm will be determined on routine angiograms until the end of the period of time in which the subject may present vasospasm (D21+/-3).	From day 2 to day 21 +/- 3 days after the initial bleeding
Quantification of cerebral blood flow using DSC-MRI	Cerebral blood flow in mL/100g/min will be measured using DSC-MRI (Dynamic Susceptibility Contrast Magnetic Resonance Imaging)	At day 4 +/- 1 day after the initial bleeding
Quantification of cerebral blood flow using ASL-MRI	Cerebral blood flow in mL/100g/min will be measured using ASL-MRI (Arterial Spin Labelling Magnetic Resonance Imaging)	At day 4 +/- 1 day after the initial bleeding
Quantification of blood-brain-barrier permeability using DSC-MRI	The blood-brain barrier permeability will be measured using DSC-MRI. A kinetic modeling will be performed in order to provide the leakage parameter K2 (in min-1) in every voxel.	At day 4 +/- 1 day after the initial bleeding
Quantification of blood-brain-barrier permeability using DCE-MRI	The blood-brain barrier permeability will be measured using DCE-MRI (Dynamic Contrast-Enhanced Magnetic Resonance Imaging). A kinetic modeling will be performed in order to provide the leakage parameter Ktrans (in min-1) in every voxel.	At day 4 +/- 1 day after the initial bleeding

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier
• Investigators: Principal Investigator: Kévin CHALARD, M.D., UH Montpellier

Study record dates

Study Major Dates

• Study Start (Actual): July 22, 2020
• Primary Completion (Anticipated): July 1, 2024
• Study Completion (Anticipated): August 1, 2024

Study Registration Dates

• First Submitted: April 15, 2020
• First Submitted That Met QC Criteria: April 17, 2020
• First Posted (Actual): April 22, 2020

Study Record Updates

• Last Update Posted (Estimate): January 26, 2023
• Last Update Submitted That Met QC Criteria: January 24, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Positron emission tomography; Delayed Cerebral Ischemia; Aneurysmal subarachnoid haemorrhage; Cerebral microcirculation
• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Infarction; Stroke; Brain Infarction; Intracranial Hemorrhages; Brain Ischemia; Ischemia; Hemorrhage; Cerebral Infarction; Subarachnoid Hemorrhage; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Fluorodeoxyglucose F18
• Other Study ID Numbers: RECHMPL19_0408

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Sharing Time Frame: 12 months after the main publication
• IPD Sharing Access Criteria: Data are provided to qualified investigators free of charge. Required documents to request data include a summary of the research plan, request form, and IRB review. Dataset will be shared after careful examination by the study board of investigators.
• IPD Sharing Supporting Information Type: Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No