Acetazolamide Challenge With Perfusion in the Prediction of Cerebral Vasospasm

July 26, 2023 updated by: University of Wisconsin, Madison

C-arm Cone Beam CTA and CTP With Acetazolamide Challenge in Aneurysmal Subarachnoid Hemorrhage: Evaluating Predictability for Early Ischemia in Cerebral Vasospasm

The investigators propose a technique using cone beam CT perfusion (CBCTP) imaging with an acetazolamide challenge as a potential diagnostic tool to detect a defect in cerebral autoregulation at a time when it has not yet caused clinically apparent signs or symptoms. 30 participants will be enrolled at the University of Wisconsin - Madison and can expect to be on study for about 2 weeks.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Acetazolamide or vasodilatory challenge should identify subjects having a abnormal cerebrovascular reactivity capacity. More specifically, after receiving the drug there will not be the expected increase in cerebral blood flow (CBF) in some of the subjects because they are already suffering from a disturbance in the vasculature's ability to respond to the signal for vasodilation. The investigators believe the presence of this deficit will be helpful in identifying patients who are at risk for potential brain ischemia due to this decreased capacity to autoregulate if/when clinically significant vasospasm occurs. The investigators predict that acetazolamide-activated regional cerebral blood flow studies will be more sensitive in the detection of mild cerebral vasospasm and will not just detect changes in cerebral blood flow as does standard perfusion imaging, but will provide information regarding changes in cerebrovascular reactivity. Under these circumstances, a better predictor of those patients at risk of cerebral infarction due to delayed vasospasm would be delineated. Identifying this "high-risk cohort" prior to the onset of clinically apparent symptoms would result in the institution of preventative measures such as triple H therapy.

The objective of this proposal is to conduct a feasibility study of acetazolamide activated C-arm cone beam CT perfusion (CBCTP) to determine its application in the prediction of symptomatic cerebral vasospasm (i.e. ischemia or stroke) in patients with aneurysmal subarachnoid hemorrhage. The initial plan is to obtain C-arm CBCTP pre- and post-intravenous infusion of 1g acetazolamide within 24 hours of symptom onset in aneurysmal subarachnoid hemorrhage patients. The hypothesis is that some of these patients that will later develop clinical vasospasm of a degree sufficient to cause cerebral ischemia. The investigators believe this cohort of patients will demonstrate altered cerebrovascular reactivity during the acetazolamide challenge at a time before there is either angiographic evidence of vasospasm or clinical evidence of abnormal perfusion.

Study Type

Interventional

Enrollment (Actual)

11

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients with aneurysmal subarachnoid hemorrhage presenting to our institution within 24 hours of symptom onset
  • Adults, 18 years of age or older
  • Women of childbearing potential must not be pregnant (negative urine pregnancy test)

Exclusion Criteria:

  • Contraindication to acetazolamide (i.e. sulfonamide allergy, renal or liver failure)
  • Contraindication to contrast media (Allergy or abnormal serum Cr and/or GFR based on current UW guidelines for IV contrast)
  • Renal insufficiency, history of renal failure or renal transplant
  • Hunt and Hess grade 1 and 5 (Attached protocol provides details on the grading scale. Grade 1 have lowest yield for vasospasm and Grade 5 are by definition critically ill and unstable patients)
  • Critically ill patients who are unstable and who cannot undergo scans within the proposed timeline i.e. within 24 hours of the onset of their symptoms.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Acetazolamide Challenge
Participants entered into the study as a cohort, will because of their participation, undergo only two additional digital subtraction angiogram (DSA) imaging acquisitions. These will be done in conjunction with their standard diagnostic DSA evaluation and consist of two CBCTPs, one before and one after administration of 1 g acetazolamide through a peripheral IV line. Each CBCTP will require administration of 75-100 mL iodinated contrast medium also through an intravenous line. Neither of these imaging studies will be used for clinical decision making, but would be processed and evaluated at later date for a formal analysis of the results. Following completion of diagnostic imaging subjects will receive the usual standard of care for treatment of their ruptured aneurysm i.e. endovascular embolization or open surgical clipping.
Drug: Acetazolamide
1 g acetazolamide through a peripheral IV line
Other Names:
  • Diamox

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants Who Develop Delayed Cerebral Vasospasm
Time Frame: Day 1-14 during the hospitalization
Clinical neurological deterioration not attributable to other causes, mores specifically not due to re-bleeding, hydrocephalus, or metabolic changes.
Day 1-14 during the hospitalization

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Relative Percent Change in Cerebral Blood Flow
Time Frame: pre and post perfusion during imaging procedure, up to an hour
The data that will be statistically compared is the pre-diamox perfusion in comparison to the post-diamox perfusion. A statistically significant change increase in CBF represents an appropriate response to Diamox. Lack of change in CBF or decrease in CBF could be suggestive of potential for developing vasospasm.
pre and post perfusion during imaging procedure, up to an hour
Percent Change in Left Hemisphere Brain Imaging Maps
Time Frame: pre and post perfusion during imaging procedure, up to an hour
Using perfusion map values, relative percent change will be calculated
pre and post perfusion during imaging procedure, up to an hour
Percent Change in Right Hemisphere Brain Imaging Maps
Time Frame: pre and post perfusion during imaging procedure, up to an hour
Using perfusion map values, relative percent change will be calculated
pre and post perfusion during imaging procedure, up to an hour

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Wisconsin, Madison

Investigators

  • Principal Investigator: Azam Ahmed, MD, University of Wisconsin, Madison

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 28, 2019

Primary Completion (Actual)

July 15, 2022

Study Completion (Actual)

July 15, 2022

Study Registration Dates

First Submitted

December 13, 2017

First Submitted That Met QC Criteria

December 13, 2017

First Posted (Actual)

December 19, 2017

Study Record Updates

Last Update Posted (Actual)

July 27, 2023

Last Update Submitted That Met QC Criteria

July 26, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2017-1510
  • A535700 (Other Identifier: UW Madison)
  • SMPH/NEURO SURG/NEURO SURG (Other Identifier: UW Madison)
  • Protocol Version 4/28/2020 (Other Identifier: UW Madison)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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