Recruiting Patients with a Recent Diagnosis of PML or Stroke for a Non-Invasive Brain Stimulation Study

April 26, 2018

You may be eligible for a research study being conducted at Beth Israel Deaconess (Boston, MA) and Northwestern University (Chicago, IL). This study is for adults who were recently (less than 1 year ago) diagnosed with Progressive Multifocal Leukoencephalopathy (PML) or a stroke.

During this study we will use a technique called transcranial magnetic stimulation (TMS) and another called electroencephalography (EEG). TMS is a noninvasive way of stimulating the brain and EEG is a way to measure your brain activity.

The study involves one to three visits which last about 3-4 hours long.

To be a part of this study, you should:

• Have been diagnosed with PML (as determined by your referring clinician) less than a year ago or
• Have been diagnosed with a stroke (as determined by your referring clinician) less than a year ago.
• Be 18-75 years of age.

If you qualify to take part in the study, all study related visits and testing are performed at no cost to participants.

Parking and travel will be reimbursed for each study visit and you will be compensated for your participation.

If you are interested, or to learn more, please contact Pierre Boucher at:
pbouche1@bidmc.harvard.edu
617-667-0254

What are the goals of this study?

Epilepsy is a common complication of many acquired brain injuries such as stroke, brain infections, and traumatic brain injury. However, any one person’s likelihood of acquiring epilepsy after a brain injury is usually low, and there are no tests to help identify which individuals are particularly likely to develop seizures. As a result, research to help prevent acquired epilepsy in patients has been difficult. Furthermore, there are no approved treatments that directly affect the brain processes involved in the development of epilepsy.

We will utilize a noninvasive brain stimulation technique, Transcranial Magnetic Stimulation (TMS), in combination with electroencephalography (EEG) to evaluate brain excitability, and thereby the risk of developing epilepsy, in patients with an acquired brain infection called Progressive Multifocal Leukoencephalopathy (PML).

Adults who have been diagnosed with a prior stroke or PML (with or without a prior diagnosis of seizures or epilepsy) may be eligible for this study.

What are the possible outcomes of this study?

Using TMS-EEG, we will determine whether patients with PML and epilepsy have increased brain excitability relative to PML patients without epilepsy and healthy controls at the presumed seizure focus.

What are the outcome measures collected in this study?

Primary outcome measure: The amount of brain excitability at the seizure focus as measured with TMS-EEG.

What are the exclusion criteria for this study?

• Uncertainty regarding the diagnosis of PML or stroke
• Uncertainty regarding whether patient has ever suffered epileptic seizures (only for PML or stroke patients without a confirmed diagnosis of Epilepsy or seizures) or significant uncertainty if a stroke patient suffered an acute symptomatic seizure
• Any confirmed diagnosis or condition known to cause non-epileptic seizures
• Suspicion for or a history of psychogenic nonepileptiform spells
• Cerebral palsy; history of severe head injury; current intracranial pathology or lesion from a known genetic disorder (e.g., NF1, tuberous sclerosis) or from acquired neurologic disease (e.g. tumor) OTHER than PML or stroke
• Any evidence of increased intracranial pressure
• Any unstable medical condition
• Prior brain surgery (excluding brain biopsy)
• Pregnancy. All female participants of child bearing age are required to have a pregnancy test
• Any metal in the brain, skull or head (not including dental work)
• Any medical devices (i.e. cardiac pacemaker, deep brain stimulator, medication infusion pump, cochlear implant, vagal nerve stimulator) unless otherwise approved by the responsible MD

Are there any risks to participating in this study? If so, what are they and what are the chances they will occur?

This study involves the use of TMS targeting the seizure focus in combination with EEG to investigate cortical excitability in patients with epilepsy, or at risk for developing seizures due to PML or stroke. TMS has been widely used since 1984, and is FDA-approved (and widely used) for treatment of refractory depression, migraines, and for presurgical mapping. TMS is generally very well tolerated. The risks and side effects of TMS include the following:

More Common Side Effects:

• Pain:
  • TMS can cause muscles of the scalp, neck, or face to twitch. This feeling may range from strange to uncomfortable and could lead to scalp pain, muscle tension or headache.  As many as 20-40% of those having TMS experience headaches – that is 4 in 10 participants. Headache or tension from TMS will usually be relieved with a single dose of acetaminophen (Tylenol®) or ibuprofen.

Less Common or Rare Side Effects:

• Seizures (are less common for participants who have seizures and are rare for those who do not):
  • TMS has in rare instances caused a seizure when used in research studies in subjects without a history of prior seizures. However, the risk of seizure is very low (less than 1 in 1000 participants and in less than 1 in 100,000 TMS sessions), and seizures have occurred primarily in participants with risk factors for suffering a seizure on that particular day (e.g. because of heavy alcohol use the night prior to the TMS session.)
  • If you do have seizures, it is possible that you could experience a seizure during TMS, although the risk is less than 2% for patients with known epilepsy. Typically, the type of seizure a patient experiences while undergoing TMS is identical to those he or she usually experiences.
  • Most seizures experienced during TMS occurred prior to the development of current safety guidelines, which are in place to minimize the risk of seizures and will be used in this study. TMS has never caused a prolonged seizure (known as status epilepticus) or a worsening of a participant’s prior seizure disorder.

Rare Side Effects:
* There is less than a 2% chance of the occurrence of the following rare side effects.

• Hearing Problems
  • The TMS procedure includes a loud clicking noise throughout. It is possible that you could experience a temporary change in your hearing.  There is one report in the literature of someone who’s hearing protection fell out who experienced permanent hearing loss from TMS.  You will wear earplugs during the TMS to reduce the noise to prevent the risk of hearing problems.  We will ask you to let us know immediately if:
    • your ear plug loosens
    • your ear plug becomes detached
    • your ear plug falls out
  • You will be promptly referred for auditory assessment if you experience hearing loss, ringing in the ear, or ear fullness following completion of the TMS.
  • You may also have ringing in your ear due to the loud clicking sound during the TMS.
• Syncope (Fainting):
  • It is possible that you could faint during the TMS.  This happens in less than 1% of people.  Fainting can happen if you are anxious, nervous or have not eaten. You should immediately tell the study staff if you feel:
    • dizzy
    • lightheaded
    • that you might pass out
  • If you have the above symptoms, the TMS will be stopped. You will be monitored until you are feeling better.
• Memory
  • TMS can very rarely cause changes in memory, attention and other cognitive (thinking) functions which may last for several minutes to several hours. However, none of these effects have been reported to be lasting, they are very mild, and they seem to be extremely rare.
• Pregnancy
  • The effects of TMS on a developing fetus are unknown.  If you are a woman capable of getting pregnant, you will be required to take a pregnancy test before TMS will be given.

TMS does not use ionizing radiation. Although TMS has been used worldwide since 1984, there may be complications that are not yet known.

Will I be compensated for this study?

Subjects will be compensated $40/hr for their time. This information is subject to change, so please contact the Pierre Boucher for more information: Pbouche1@bidmc.harvard.edu.

Is transportation assistance available?

Yes, transportation assistance is available.

Are there limitations in transportation assistance?

Travel costs up to $500/session and hotel costs up to $200 for one night (for out-of-town participants) will be covered. This information is subject to change, so please contact the Pierre Boucher for more information: Pbouche1@bidmc.harvard.edu.

Will my information remain private?

Information learned from your participation in this study and from your medical record may be reviewed and photocopied by the Food and Drug Administration (FDA) and/or other federal and state regulatory agencies, and by the device manufacturer (Nexstim, Inc and MagPro) manufacturer, accreditation agencies, the Committee on Clinical Investigations, the Human Subjects Protection Office and others involved in research administration of the Beth Israel Deaconess Medical Center with protection of confidentiality so far as permitted by applicable law.  Information resulting from this study and from your medical record may be used for research purposes and may be published; however, you will not be identified by name in such publications.

What is required of me?

You will have at least 1 visit for a TMS-EEG session. This visit will take approximately 5 hours. During this time, you will receive single pulses of TMS administered every 4-6 seconds, with simultaneous EEG monitoring. Depending on your individual history, you may be asked to return for 1-2 additional TMS-EEG sessions within the two years following the initial visit.

What is my role in the study? Am I a healthy volunteer or a patient volunteer?

Your role in the study is to be a patient volunteer, to help us develop better tests to predict and diagnose seizures in patients at high risk for developing acquired epilepsy.

What are my chances of being in the placebo group?

There is no placebo group in this study; all participants will receive active stimulation.

Will the study directly benefit me?

We do not anticipate that this study will benefit you directly. Results of the study will not be returned to participants directly.

Will the study benefit others?

Yes. This study will help us understand more about the changes in brain excitability that occur in patients with acquired epilepsy, and how those changes occur over time. This knowledge may help us develop better tools to diagnose patients with epilepsy, identify subjects with a high risk of developing seizures after a brain injury, and provide a measure to follow to predict how individual patients will respond to medical therapy.

What discomforts are involved?

See question 1 about risks of TMS above.

What is the total time involved?

Each session will take about 5 hours. Depending on your personal history, you may be asked to participate in 1-3 sessions (so 12-15 hours max).

Are there other inconveniences?

No, there are no other inconveniences.

What is the enrollment timeframe for this study?

This study is currently underway and enrolling. It is estimated that patients will continue to be enrolled until October 2019.

What are the enrollment site(s) for this study?

Beth Israel Deaconess (Boston, MA) and Northwestern University (Chicago, IL).