[Photo of National Institutes of Health Clinical Center]

MEadvocacy attended the National Institutes of Health [NIH] telebriefing on March 8th, 2016.  

We issued a blog on March 9th with the question that we posted to NIH and the reply we received.

In this blog, we are giving the highlights of several presentations from NIH and National Institute of Neurological Disorders and Stroke [NINDS] regarding intramural and extramural NIH research.  Many questions and concerns still remain, with some additional new ones. We will follow up with a blog with commentary on the call and the new protocol posted on the NIH website.

The NIH telebriefing audio file, released to us, is now available here.

NIH Presentations

Summary of opening remark by NIH director, Dr. Francis Collins

Dr. Collins personally welcomed us to what he hoped will be an ongoing conversation about ME/CFS research. “...and how we can move the needle forward together when characterizing the cause of this perplexing disorder to help with better diagnosis and treatment.”

He stressed that the institute and director are very committed to move the science forward; with the intramural activities as well as extramural programs.

Highlights:

• The intramural study protocol received institutional review board (IRB) approval.

• They will begin enrolling patients this summer.

• The website with detailed information on intramural protocol went up March 8th (link).

• It’s a remarkable opportunity to use world class NIH clinic and their interdisciplinary hospital.

• There’s heterogeneity in this condition.

• Focus is on sudden onset with flu like illness in order to limit heterogeneity.

• Trans-NIH ME/CFS Working Group [TNWG] is planning to define strategic areas of research that could form the basis for short and long term extramural applications.

• Looking to recruit new eyes/brains/investigators to the field to solve the puzzles.

Dr. Collins reaffirmed his commitment and asked patients to stay the course.  He knows many patients have waited a long time.  He concluded by saying that we should work together not apart. He said NIH is listening carefully to patients’ and advocates’ comments and suggestions.

Summary of presentation by NINDS director, Dr. Walter Koroshetz

He thanked everyone for expressing their interests and concerns.  He is very interested in working together toward a long term common goal.  

Highlights:

• This is a difficult problem or else it would have been solved long ago.

• They need to bring in the best and the brightest from many areas of science.

• They need expert clinicians and researchers.

• NIH has an extramural program where funds go to universities and other institutions to do research.

• The intramural program is when research is done at the NIH clinic in Bethesda, Maryland which is largest research hospital in the world.

• 90% of the NIH’s funds go to the extramural branch.

• The Trans-NIH ME/CFS Working Group [TNWG] brings scientists and funding together from many institutes. This is important because we don’t know where the solution will come from.

• The TNWG is devising plans to move funds to highly meritorious extramural research proposals.

Summary of presentation by a program director at NINDS , Dr. Vicky Whittemore

Thanked us for being on call.  She has been working with Dr. Koroshetz to coordinate the TNWG.

She works with representatives from the staff of the 23 NIH institutes and centers who are passionate and dedicated about this work.

Highlights:

• They are in the process of putting together both short term and long term plans.

• The priorities are to find biomarkers, causes and mechanisms that lead to ME/CFS.

• They want to understand what is causing ME/CFS brainfog and cognitive symptoms.

• They are working very hard to present initiatives to the appropriate councils for approval, in the May timeframe.

They are looking forward to input and feedback from ME/CFS community.  Some of the ways are to put out specific requests for feedback on different ideas they have, with follow-up conference calls, as well as getting feedback from the research and clinical community.

Koroshetz added a note to clarify:  ”...people are wondering out there, ‘Why can’t we actually say what we are thinking?’"  But, NIH has processes that ensure the research that comes in and the most meritorious research is funded and that all groups have a fair hearing. Therefore, NIH cannot divulge information until they can make it public to everyone.

Summary of presentation by primary investigator, Dr. Avindra Nath

Dr. Nath stated that he was delighted to be asked by Dr. Collins and Dr. Koroshetz to be the principal investigator of this intramural study. 

He was thrilled to be able to look at the syndrome and see if there is an immune or neuroimmune component here that maybe driving the disease. This is the area of his expertise. He has seen patients and knows how devastating it can be.

Highlights:

The literature indicates it is likely immune mediated, and the protocol he designed addresses these issues.
There are three phases to the study:

1. cross sectional study - a lot of investigation on a small group of patients

2. longitudinal study - larger group of different patient population for a longer period of time with a repeat of subset testing

3. Intervention study - based on first two phases will bring guidance as to what type of immune modulating therapy could work.

Summary of presentation by lead associate investigator, Dr. Brian Walitt

He is lead associate investigator for intramural protocol at NIH.  His experience starts with a career in rheumatology.

Highlights

• Has experience in hospital immune disorders with specialty in ME/CFS and fibromyalgia.

• Opened research clinic in Georgetown University to study these disorders.

• Patients taught him how real these disorders are. “they are not just in one’s head”. They do not reflect some unconscious choice. It’s not possible to simply push through the symptoms.

• Try to help patients but learned how limited the options really are

• There is an urgent need for restorative treatments to give patients their lives back.

• Learned a lot from the world class scientists at the NIH clinic.

• Wants to find answers to the big questions of ME/CFS: the role of infection, immunology and neurology in the degeneration and perpetuation of symptoms.

• Wants to find and understand the biology of post exertional malaise.

More from Dr. Koroshetz

He wanted to emphasize that 26 associate investigators will be working along with Drs. Nath and Walitt, who will bring their expertise to the table.  This includes high level neuroimaging and high level ability to look at cytokines and autoantibodies. They also have Leo Saligan from the nursing institute who has been looking at chronic fatigue in patients with cancer and rheumatological disorders.

The NIH clinic has full time devoted researchers with many resources available to them like the capability to bring patients into study for days or weeks. This study is just a stepping stone - one piece of the puzzle but an important one to coordinate with other initiatives across the country.

The presentations were followed by a Q & A session from the audience listening in on the call.  You can listen to the questions and replies on the audio file.  The Q & A section starts at 20:00 minutes. 

Some highlights from the protocol listed on new NIH website

This is the first phase of the research project.  It will take place at the NIH clinic in Bethesda, Maryland.

Criteria:

• The Canadian Consensus Criteria (CCC) will be used for all ME/CFS patients.

• They will all be objectively tested for post exertional malaise (PEM).

• They will be screened with validated functional scales to measure severity.

Other Characteristics for selection:

They are selecting sudden-onset post-infectious ME/CFS patients who have been sick between 6 months to 5 years.

Selection Review:

Most patients will be recruited from well-established ME/CFS clinics that are being supported by the CDC in the Multi-site Clinical Assessment of CFS study.

In addition, the following experts on the executive committee will review the selection of patients:

• Dr. Elizabeth Unger from the CDC  (http://www.cdc.gov/cfs/news/cvbd/)

• Dr. W. Ian Lipkin from Columbia University. https://www.mailman.columbia.edu/people/our-faculty/wil2001)

A final assessment of diagnostic validity will be performed by a team of clinical experts at NIH, including:

• Dr. Fred Gill (http://clinicalcenter.nih.gov/about/SeniorStaff/fred_gill.html)

• Dr. Leorey Saligan (http://irp.nih.gov/pi/leorey-saligan)

• Dr. Brian Walitt (https://www.ninr.nih.gov/researchandfunding/dir/bwalitt#.VrzwHNv2aAI)

Control Groups:

They will start with a healthy control group and a recovered post-lyme group.  They are discussing the addition of other control groups.

Why the choice of post-Lyme patients?  Since they are focusing on the post-infectious ME/CFS cohorts, they think it would be useful to compare them against a cohort that also had an infection but then fully recovered.  (Many Lyme patients already have been evaluated at the NIH.)

Start of Patient Selection:

They anticipate enrolling patients starting summer of 2016.

Screening Procedures Will Include: (should last 2 to 3 days)

• Initial phone screening.

• In-person screening visit.

• One-week inpatient stay at the NIH Clinical Center.

Brief Description of Procedures:

Initially

• Completion of a telephone screening with the study staff.

• An explanation of the study and signing of the research study consent form.

• Medical history.

• Physical exam.

• Blood and urine collection.

• Questions about the participant’s life and their quality of life.

• Questions about the participant’s mental health.

Follow Up

• Magnetic resonance imaging (MRI). Participants will lie in a machine that takes pictures of their brain. They may get a dye through an intravenous (IV) line that is placed in their arm. (A thin plastic tube inserted into a vein).

• Hand grip strength test.

• Saliva test for virus testing.

• Tests of body functions such as sweating and breathing, blood pressure while standing upright, sitting and lying, and heart rate.

• Collection of blood cells. Participants can choose to have the blood drawn through the IV or through a machine that filters blood cells and returns the liquid blood back into the participants' vein.

• An explanation on how to wear an activity monitor and complete a fatigue diary. Participants will use these tools to record their activity and fatigue symptoms for at least one week, once they are back at home.

• Review of medications. Participants may be asked to taper off certain medicines that affect the brain and nerves.

Selected patients will go home and taper off medications, they will also use an activity monitor and a fatigue diary. Within 6 months of first visit, the participants will return for a one week inpatient hospital visit.

During inpatient visit, participants will perform a stationary bike exercise test twice. The purpose of the exercise test is to make participants tired and to try to evoke symptoms, such as 'post-exertional malaise'. Tests will be performed before and after exercise testing.

Tests Will Include:

• Questions about how participants are feeling.

• Samples of saliva, stool, and a cheek swab to test stress hormones and the types of bacteria living in the mouth and gut.

• Thinking and memory tests.

• Overnight heart monitoring.

• Transcranial magnetic stimulation. A brief magnetic pulse from a magnet held over the scalp can affect brain activity and will be used to examine what brain excitability changes occur with muscle fatigue.

• Imaging studies such as an X-ray and magnetic resonance imaging (MRI). During an MRI participants will lie in a machine that takes pictures of their brain. They will do thinking and exercise tasks during the MRI to examine what changes in brain activity occur with different types of fatigue.

• Lumbar puncture. Fluid will be removed by placement of a needle between the back bones.

Note:  In reply to a question posed by Charmian Proskauer about the small size of patient cohort (40), Dr. Nath replied that only one patient will be studied for a week at a time.  It will take at least 40 weeks just to study the ME/CFS cohort group.