Aspirin Attenuates Inflammation in Human Cerebral Aneurysms
Condition: The Focus of the Study is to Monitor MRI Signal Changes and Inflammatory Biomarkers With Use of Aspirin in Patients With Unruptured Cerebral Aneurysm
MeSH terms: Intracranial Aneurysm; Aneurysm; Inflammation
Study type: Interventional
Phase: Phase 1

Summary: 
      Hypothesis: aspirin attenuates inflammation in cerebral aneurysms and hence reduces the
      incidence of rupture. This effect can be monitored using the signal generated by macrophages
      (inflammatory biomarker) in ferumoxytol-enhanced MRI.

      Study aims:

      1. Determine if daily aspirin intake (for three months) would obliterate/reduce
      ferumoxytol-enhanced MRI signal changes generated by macrophages in cerebral aneurysm wall.
      Fifteen patients with cerebral aneurysms > 7 mm will be selected to enroll in this pilot
      study. 10 patients will be imaged at base line with ferumoxytol-enhanced MRI. Following that,
      they will take aspirin 81 mg daily and then re-imaged again at three months. This group will
      be compared to a control group of 5 patients where they will have the imagings studies
      performed at base line and at three months but will NOT take aspirin.
    

Detailed description: 
      If you are eligible to enroll in the study, you will be contacted by the principal
      investigator in person and he will describe the study in a private setting (neurosurgery
      clinic room or hospital patient room). You will be given ample opportunity to decide to
      participate or not.

      You will be randomly assigned to receive one of the 2 study treatments, either taking aspirin
      or not. This means that whichever study treatment you receive will be determined purely by
      chance, like flipping a coin. You will have a 2 out of 3 chance of receiving the study
      treatment (aspirin). You will be told which study treatment arm you are on.

      A 15 minute base line MRI of the brain will be performed initially. Following that, the
      medication (ferumoxytol) will be injected intravenously over 3 minutes. The second MRI of the
      brian will obtained 24 hours later. A third MRI will be obtained also at 72 hours following
      the injection of medication. Then after the third MRI, ten people will be chosen randomly to
      start aspirin every day for three months total. The selected aspirin group will be given
      3-month supply of aspirin (81 mg). The other five patients will be asked to avoid any
      anti-inflammatory drugs (like aspirin, Advil, ibuprofen, …) if at all possible. Following an
      interval of three months, a repeat MRI of the brain will be done exactly as above (a base
      line MRI of the brain will be done, then the medication will be injected intravenously (IV).
      A second MRI will be obtained 24 hours later followed by another one at 72 hours later.

      MRI scans:

      An MRI scanner takes pictures of the inside of your brain. You will be asked to lie on your
      back on a special table that slides into the tube. The sides of the tube will be fairly close
      to your body and the scanner makes a loud hammering noise while you are inside. You will be
      able to talk to people in the room through a speaker system. We will monitor you closely
      while you are inside the scanner.

      The MRI images for this study are not being used to evaluate your health. The images obtained
      for this study are for specific research purposes and are not being used to find medical
      abnormalities. These images will not be reviewed by a radiology physician to diagnose
      existing abnormalities.

      Sequence of events:

        1. Informed consent will be obtained.

        2. Serum pregnancy test (if you are a female of child bearing age) and blood chemistry labs
           will be collected. If the results are positive, you will not be able to continue in the
           study.

        3. IV access will be inserted.

        4. 15-30 minutes base-line MRI will be performed

        5. The study medication, ferumoxytol, will be given to you via IV line immediately after
           the first MRI

        6. The second MRI will be obtained 24 hours later

        7. The third MRI will be obtained 72 hours following infusion of ferumoxytol.

        8. You will be selected randomly to either receive aspirin or not.

        9. Ten patients will be assigned to start taking aspirin (325mg) every day for 3 months.

       10. Five patients will be asked to avoid any anti-inflammatory drugs (like aspirin, Advil,
           ibuprofen…) for three months if all possible.

       11. At three months, another base-line MRI will be performed

       12. The study medication, ferumoxytol, will be given to you via IV line immediately after
           the first MRI

       13. The second MRI will be obtained 24 hours later

       14. The third MRI will be obtained 72 hours following infusion of ferumoxytol

       15. Study is finished

      WHAT ARE THE RISKS OF THIS STUDY? What are the risks of the study? You may experience one or
      more of the risks indicated below from being in this study. In addition to these, there may
      be other unknown risks, or risks that we did not anticipate, associated with being in this
      study.

      Aspirin:

      1. Nausea 2. Vomiting 3. Stomachache/burn 3 Stomach pain suggestive of stomach ulcer 5. Black
      stool suggestive of rectal bleeding 6. Dizziness 7. Rash 8. Fever

      Ferumoxytol:

        1. Diarrhea (4%),

        2. nausea (3.1%),

        3. dizziness (2.6%),

        4. hypotension (2.5%),

        5. constipation (2.1%),

        6. swelling of the legs, arms and/or face (2%),

        7. headache (1.8%),

        8. edema (1.5%),

        9. vomiting (1.5%),

       10. abdominal pain (1.3%),

       11. chest pain (1.3%),

       12. cough (1.3%),

       13. rash (1%),

       14. muscle spasm (1%),

       15. back pain (1%),

       16. hypertension (1%),

       17. shortness of breath (1%),

       18. itching (1%).

       19. life-threatening or severe allergic reaction that could lead to death

      MRI Scan:

      You may be uncomfortable inside the MRI scanner if you do not like to be in closed spaces
      ("claustrophobia"). During the procedure, you will be able to talk with the MRI staff through
      a speaker system. You can tell them to stop the scan at any time.

      The MRI produces a loud hammering noise, which has produced hearing loss in a very small
      number of patients. You will be given earplugs to reduce this risk.

      Loss of confidentiality:

      1. your name, diagnosis, age, gender and potential treatment could be accessed by
      non-research team individuals.

      Intravenous Catheter Insertion:

      For this study you will need to have small amount of blood drawn for laboratory studies to
      make sure that it is safe for you to participate in the study. You will have an intravenous
      catheter (IV) placed peripherally (usually arm or hand) for infusion of the study drug,
      ferumoxytol. There are minimal risks associated with placement of the IV, including pain,
      bleeding, bruising, and infection at the IV site.

      Women Capable of Becoming Pregnant If you are a woman who is capable of becoming pregnant, we
      will ask you to have a pregnancy test before beginning this study. You must use effective
      birth control methods and try not to become pregnant while participating in this study. If
      you become pregnant, there may be unknown risks to your fetus, or risks to your fetus that we
      did not anticipate, associated with being in the study. There may be long-term effects of the
      treatment being studied that could increase the risk of harm to an unborn child. If you
      believe or know you have become pregnant while participating in this research study, please
      contact David Hasan 319-384-8669 as soon as possible.

      WHAT ARE THE BENEFITS OF THIS STUDY? You will not benefit from being in this study.

      However, we hope that, in the future, other people might benefit from this study because it
      may inform us if taking aspirin daily would help stabilize the aneurysm wall and reduce the
      risk of rupture.

      WHAT OTHER TREATMENT OPTIONS ARE THERE?

      Before you decide whether or not to be in this study, your doctor will discuss the other
      options that are available to you. Instead of being in this study, you could undergo
      microsurgical clipping of your aneurysm, have your aneurysm treated endovascularly by placing
      coils in the aneurysm sac, or just observe your aneurysm and monitored with imaging studies.

      WILL IT COST ME ANYTHING TO BE IN THIS STUDY?

      You will not have any additional costs for being in this research study. All the costs
      associated with MRIs and the injections will be covered by the study. There may be additional
      costs associated with travel to and from visits.

      You and/or your medical/hospital insurance carrier will remain responsible for your regular
      medical care expenses.

      WILL I BE PAID FOR PARTICIPATING?

      You will not be given any direct compensation for being in this research study. However, the
      study will pay for any hotel accommodation that may be given should you need lodging between
      MRI visits.

      WHO IS FUNDING THIS STUDY?

      The University and the research team are receiving no payments from other agencies,
      organizations, or companies to conduct this research study.

      WHAT IF I AM INJURED AS A RESULT OF THIS STUDY?

        -  If you are injured or become ill from taking part in this study, medical treatment is
           available at the University of Iowa Hospitals and Clinics.

        -  The University of Iowa does not plan to provide free medical care or payment for
           treatment of any illness or injury resulting from this study unless it is the direct
           result of proven negligence by a University employee.

        -  If you experience a research-related illness or injury, you and/or your medical or
           hospital insurance carrier will be responsible for the cost of treatment.

      WHAT ABOUT CONFIDENTIALITY? We will keep your participation in this research study
      confidential to the extent permitted by law. However, it is possible that other people such
      as those indicated below may become aware of your participation in this study and may inspect
      and copy records pertaining to this research. Some of these records could contain information
      that personally identifies you.

        -  federal government regulatory agencies,

        -  the U.S. Food and Drug Administration

        -  auditing departments of the University of Iowa, and

        -  the University of Iowa Institutional Review Board (a committee that reviews and approves
           research studies)

      To help protect your confidentiality, you will not be identified by name, social security
      number, address or phone number. The hard copy and electronic records will include a code
      number and initials. The list that matches your name with the code number will be kept in
      password protected computer file in Dr. Hasan's locked office. Also the hard copies of your
      study material will be kept in locked file cabinets in a locked office. If we write a report
      or article about this study or share the study data set with others, we will do so in such a
      way that you cannot be directly identified.

      The University of Iowa Hospitals and Clinics generally requires that we document in your
      medical record chart that you are participating in this study. The information included in
      the chart will provide contact information for the research team as well as information about
      the risks associated with this study. We will keep this Informed Consent Document in our
      research files; it will not be placed in your medical record chart.

      IS BEING IN THIS STUDY VOLUNTARY?

      Taking part in this research study is completely voluntary. You may choose not to take part
      at all. If you decide to be in this study, you may stop participating at any time. If you
      decide not to be in this study, or if you stop participating at any time, you won't be
      penalized or lose any benefits for which you otherwise qualify.

      What if I Decide to Drop Out of the Study?

      If you decided to drop out of the study, you will not suffer any adverse consequences
      (physical, social, economic, legal or psychological).

      Will I Receive New Information About the Study while Participating? If we obtain any new
      information during this study that might affect your willingness to continue participating in
      the study, we'll promptly provide you with that information.

      Can Someone Else End my Participation in this Study? Under certain circumstances, the
      researchers might decide to end your participation in this research study earlier than
      planned. This might happen if your aneurysm ruptures or becomes symptomatic.

      WHAT IF I HAVE QUESTIONS?

      We encourage you to ask questions. If you have any questions about the research study itself,
      please contact: David Hasan, MD, 319-331-1459. If you experience a research-related injury,
      please contact:

      David Hasan MD, 319-331-1459.

      If you have questions, concerns, or complaints about your rights as a research subject or
      about research related injury, please contact the Human Subjects Office, 105 Hardin Library
      for the Health Sciences, 600 Newton Rd, The University of Iowa, Iowa City, IA 52242-1098,
      (319) 335-6564, or e-mail irb@uiowa.edu. General information about being a research subject
      can be found by clicking "Info for Public" on the Human Subjects Office web site,
      http://research.uiowa.edu/hso. To offer input about your experiences as a research subject or
      to speak to someone other than the research staff, call the Human Subjects Office at the
      number above.
    

Intervention name(s): aspirin
Intervention type(s): Drug
Intervention MeSH terms: Aspirin
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Basic Science
Keywords: aneurysm, inflammation, MRI