Dr Nath's intra-mural study at NIH is currently recruiting

[Kati]

https://clinicaltrials.gov/ct2/show/NCT02669212

Name:
Myalgic Encephalomyelitis Chronic Fatigue at the National Institutes of Health

ClinicalTrials.gov Identifier:
NCT02669212
First received: January 29, 2016
Last updated: December 6, 2016
Last verified: October 2016

Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:

• To explore the clinical and biological phenotypes of post-infectious chronic fatigue syndrome (PI-ME/CFS) [ Time Frame: Week 1: Single time point measurement ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

• To explore the pathophysiologies of fatigue and post-exertional malaise (PEM). [ Time Frame: Week 2: Pre-exercise stress, 4 hours, 24 hours, and 48 hours. Additional measurement for PI-ME/CFS at 72 and 96 hrs. ] [ Designated as safety issue: No ]
  Fatigue will be explored using tasks designed to create muscular and cognitive fatigue. PEM will be explored using an exercise stress and measuring the symptomatic and biological alterations that occur before and afterwards.

Estimated Enrollment: 186
Study Start Date: January 2016
Estimated Study Completion Date: September 2018
Estimated Primary Completion Date: September 2018 (Final data collection date for primary outcome measure)
Detailed Description:
Objective:

The primary objective is to explore the clinical and biological phenotypes of post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS). The secondary objective is to explore the pathophysiology of fatigue and post-exertional malaise (PEM).

Study population:

Up to 186 persons will be enrolled as part of this protocol. Up to 150 persons aged 18-60 will be part of 3 study groups: 50 ME/CFS patients whose fatigue began after an infection, 50 non-fatigued participants with a documented history of Lyme disease exposure and treatment, and 50 healthy volunteers. The study has a target of completing all study procedures on 20 enrolled participants in each group. Up to an additional 36 persons reporting a community diagnosis of ME/CFS will be enrolled into focus groups to discuss the experience of post-exertional malaise.

Design:

This is a single-center, exploratory, cross-sectional study of PI-ME/CFS. Participants will have a phenotyping visit, which will encompass a 2-5 day long inpatient admission at the NIH Clinical Center. Case status for ME/CFS participants will be determined after the phenotyping visit by a case adjudication process utilizing an expert physician committee and published guidelines. Adjudicated participants meeting inclusion criteria will be invited back to participate in an exercise stress visit, which will encompass a 5-10 day long inpatient admission. Detailed subjective and objective measurements and biological specimens will be serially collected before and up to 96 hours after a peak exercise test capable of inducing post-exertional malaise during this visit. All procedures will be completed on all three study groups to allow for optimal inter-group comparisons.

Outcome measures:

1. Characterization of the immune system and inflammatory signaling in blood and cerebrospinal fluid (CSF)
2. Characterization of the pattern of microbiome in gut, blood and CSF
3. Characterization of physical and cognitive fatigue using functional magnetic resonance imaging and transcranial magnetic stimulation
4. Effect of maximal exertion on neurocognition
5. Effect of maximal exertion on brain function and connectivity
6. Effect of maximal exertion on markers of immune dysfunction and inflammation
7. Effect of maximal exertion on metabolic function
8. Effect of maximal exertion on autonomic function
9. Effect of maximal exertion on gene expression profiles in blood and CSF

Eligibility

Ages Eligible for Study: 18 Years to 60 Years (Adult)
Genders Eligible for Study: Both
Accepts Healthy Volunteers: Yes
Criteria

• INCLUSION CRITERIA:
• Inclusion criteria for all participants
  1. Adult participants aged 18-60 years at the time of enrollment.
  2. Self-reported completion of at least the 7th grade of school.
  3. Ability to speak, read, and understand English.
  4. Willing and able to complete all study procedures
  5. Participant has a primary care physician at the time of enrollment.
  6. Able to provide informed consent.
• Additional inclusion criteria for participants with PI-ME/CFS for the phenotyping visit
  1. A self-reported illness narrative of the development of persistent fatigue and post-exertional malaise as the consequence of an acute infection. The persistent fatigue may have an acute onset or become progressively worse over 6 months.
  2. Licensed Independent Practitioner documentation of ME/CFS onset:
     • Medical documentation of absence of symptoms within one year of ME/CFS onset.
     • Documentation of a medical evaluation for symptoms of an acute infection or documentation of a medical evaluation of persistent symptoms within 2 months following an assumed infection.
  3. Persistent fatigue and PEM onset less than 5 years prior to enrollment.
• Additional inclusion criteria for participants with PI-ME/CFS for the exercise stress visit
  1. Be unanimously considered to be a case of PI-ME/CFS by the protocol s adjudication committee.
  2. Meet the 1994 Fukuda Criteria and the 2003 Canadian Consensus Criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.
  3. Have moderate to severe clinical symptom severity:
     • Severe fatigue as determined using the Multidimensional Fatigue Inventory (MFI): score of greater than or equal to 13 on the general fatigue subscale or greater than or equal to 10 on the reduced activity subscale.
     • Functional impairment as determined using the Short-Form 36 (SF-36): score of less than or equal to 70 physical function subscale, or less than or equal to 50 on role physical subscale, or less than or equal to 75 on social function subscale
• Additional inclusion criteria for healthy volunteer group

• Additional inclusion criteria for Documented Lyme Infection Asymptomatic group
  1. Medical record documentation of fulfilling the probable or confirmed 2011 CDC Lyme Disease National Surveillance Case Definitions (http://wwwn.cdc.gov/nndss/conditions/lyme-disease/case-definition/2011/):
     1. Probable: A case of physician-diagnosed Lyme disease that meets laboratory criteria of evidence of infection (positive culture for B.burgdoferi, or two-tiered testing using criteria, or single-tier IgG immunoblot seropositivity using criteria, or CSF antibody positive for B.burgdoferi by Enzyme Immunoassay or Immunofluorescence Assay, when the titer is higher than it was in serum.
     2. Confirmed: A case of erythema migrans with a known exposure, or a case of erythema migrans with laboratory evidence of infection and without a known exposure, or a case with at least one late manifestation that has laboratory evidence of infection.
  2. Have received accepted antibiotic treatment for Lyme Disease greater than or equal to 6 months prior to enrollment but less than 5 years prior to enrollment documented in their medical records.
     
     
     EXCLUSION CRITERIA:
• Exclusion criteria for all participants
  1. Active infection (e.g. influenza, urinary tract infection) by history, physical examination, or laboratory evaluations at the time of enrollment
  2. Current or past psychotic disorder including depression with psychosis, bipolar disorder, and schizophrenia
  3. Current DSM-5-defined major depression disorder, generalized anxiety disorder, post-traumatic stress disorder, panic disorder, or obsessive-compulsive disorder unless managed for more than six months with a stable treatment regimen
  4. Current or prior substance use disorder as diagnosed on the Structured Clinical Interview for DSM-5 (SCID-5) or positive urine toxicology results at enrollment
  5. Current suicidal ideation
  6. History of head injury with loss of consciousness, or history of head injury with amnesia lasting greater than a few seconds
  7. Women who are pregnant, actively seeking to become pregnant, or have been pregnant in the year prior to study enrollment.
  8. Current or previous malignancy. Certain dermatologic malignancies (e.g. basal cell carcinoma) will be allowed.
  9. Current immunologic disorder (e.g. Type 1 diabetes, rheumatoid arthritis)
  10. Current or previous long term immune suppressive or immunomodulatory therapy. Systemic steroid use, even short-term, must not have been used within the month prior to enrollment
  11. Any medical condition (eg, congestive heart failure, coronary artery disease, chronic obstructive pulmonary disease, severe osteoarthritis, poorly controlled asthma) that would make the study procedures risky for the participant (e.g. exercise-induced angina and asthma) or that may confound the study results (e.g. untreated obstructive sleep apnea, severe osteoarthritis).
  12. Participation in a clinical protocol (e.g. anti-inflammatory drug intervention study) which includes an intervention that may affect the results of the current study.
  13. Inability to perform the bicycling exercise task.
  14. Clinically significant claustrophobia
  15. Not willing to allow for research samples to be shared with other researchers.
  16. Employees or staff at NIH that are directly supervised by the primary investigator or associate investigators.
• Additional exclusion criteria for participants with PI-ME/CFS for phenotyping visit
  1. Significant neurological disorder (e.g. neurodegenerative disorder, stroke, epilepsy).
  2. PI-ME/CFS disease severity that makes it impossible for the volunteer to leave the home or requires inpatient treatment.
  3. Suspected, probable, or confirmed Lyme disease per 2011 CDC Lyme Disease National Surveillance Case Definitions.
  4. Underlying illness that may cause fatigue such as thyroid dysfunction, hepatitis, or other systemic diseases.

See more at the link above or on the clinicaltrials.gov website

 

[Sasha]

@Kati, would it be a good idea to call this the "Nath intra-mural study" in your title, so that people realise which one it is?

 

[Denise]

Thanks for posting this!

http://go.shr.lc/2g2sKsV

See more at the link above or on the clinicaltrials.gov website

@Kati - the link seems to go to the BMJ blog post
Mind the Gap: Ethical Failures in the Treatment of Chronic Fatigue Syndrome
http://blogs.bmj.com/medical-ethics...in-the-treatment-of-chronic-fatigue-syndrome/
I think the link to the NIH clinical study is https://clinicaltrials.gov/ct2/show/NCT02669212http://blogs.bmj.com/medical-ethics...in-the-treatment-of-chronic-fatigue-syndrome/

 

[Kati]

Thanks for posting this!



@Kati - the link seems to go to the BMJ blog post
Mind the Gap: Ethical Failures in the Treatment of Chronic Fatigue Syndrome
I think the link to the NIH clinical study is https://clinicaltrials.gov/ct2/show/NCT02669212

Oops! Thanks I will correct the original post. Thank you Denise.

My head... my poor head

 

[Denise]

My head... my poor head

I hope your head (and the rest of you) are doing better soon!

 

[*GG*]

Does the NIH put out flyers for a more succinct description. Scanned it over, not sure where it is taking place, sure no place close to me. Number of visits over time is what? What is the compensation?

GG

 

[Kati]

Does the NIH put out flyers for a more succinct description. Scanned it over, not sure where it is taking place, sure no place close to me. Number of visits over time is what? What is the compensation?

GG

The best thing to do, @*GG* is to contact them directly. Please read the link carefully. There is one one location, the NIH clinical trial center in Bethesda. I do not believe there is any compensation however they will lodge you and they will feed you for the time you are there.

 

[BurnA]

Adjudicated participants meeting inclusion criteria will be invited back to participate in an exercise stress visit, which will encompass a 5-10 day long inpatient admission. Detailed subjective and objective measurements and biological specimens will be serially collected before and up to 96 hours after a peak exercise test capable of inducing post-exertional malaise during this visit. All procedures will be completed on all three study groups to allow for optimal inter-group comparisons.

This reads well.

 

[*GG*]

The best thing to do, @*GG* is to contact them directly. Please read the link carefully. There is one one location, the NIH clinical trial center in Bethesda. I do not believe there is any compensation however they will lodge you and they will feed you for the time you are there.

All set, not going to waste my time! Not worth my effort.

GG

 

[viggster]

Study requires two trips to Bethesda, Md. One for evaluation (a few days) and if they take you for the full study it will be a 5-7 day stay at the NIH Clinical Center. The study coordinator told me they'd pay travel. Not sure if there is reimbursement beyond that.

The contact is: Angelique Gavin (301) 496-1788 mecfsemail@nih.gov

 

[duncan]

So how do I streamline the application process and save US tax payers' dollars? Send my resume along with a Rorschach test directly to Wallit and company?

How do they reconcile the inclusion criteria of applicants with asymptomatic Lyme, with the exclusion criteria of anyone with Lyme that satisfies the CDC national surveillance criteria? Treatment? There are reports of individuals that satisfy the national surveillance criteria, have received treatment, and still have Lyme - indeed, satisfy both the IDSA and CDC criteria for late stage Lyme - including myself. As far as I can see from these criteria, some kind of treatment is the sole difference.

Shouldn't there be something about no symptoms for a defined period of time? The clinicaltrials.gov page leaves me uncertain.

They better get the Lyme variable right, or the entire process could be undermined.

 

[Kati]

I note that at the bottom of the page there is still "movement disorder" in their list of keywords. I hope it is simply a mistake, and forgot to delete that keyword.

Keywords provided by National Institutes of Health Clinical Center (CC):
Chronic Fatigue Syndrome
Lyme Disease
Healthy Volunteers
Movement Disorder

 

[Valentijn]

So how do I streamline the application process and save US tax payers' dollars? Send my resume along with a Rorschach test directly to Wallit and company?

Hopefully they'll be publicly embarrassed enough by the involvement of quacks at the NIH that they'll stop hiring them or featuring them in projects like these.

 

[viggster]

In case anyone is interested, here is the informed consent form. It has a lot of details about the protocol - 17 pages of detail. You can also find it at https://mecfs.ctss.nih.gov/ under "consent forms".

Someone asked about compensation. Travel to and from Bethesda is paid by NIH. Here's the rest of the info from the form:

"Compensation for completing the first study visit will be $490. Those who have cytapheresis will receive an additional $110. Compensation for completing the exercise stress visit will be $1,005.
If you are unable to finish the study, you will be paid for those parts you complete."

 

[viggster]

A bit more info on the study, from my phone conversation with one of the researchers:

- Volunteers will see results from basic tests, like blood tests, done at NIH. But patients won't have access to the research test results, namely because there's no way to interpret them while the study is in progress. (E.g. Patients won't see their fMRI results.)
- The two visits to NIH could be several months apart. The second visit includes physical (bicycle) & cognitive (math problems) exercise to induce PEM.
- Volunteers will need to come off all meds for the second visit, but not the first.
- Patients will get a FitBit to wear between visits.
- The transcranical magnetic stimulation is being done to stimulate & tire out a specific set of muscles, likely in the wrist. This technology can trigger muscle movement in specific areas of the body, and the idea is to tire out one group of muscles and study them in that fatigued state.
- A nutritional component has been added...all food will be closely monitored and a nutritionist is involved in the study now. My brain was fading at this point in the conversation so I don't recall many details.

 

[duncan]

The NIH should release volunteers' records as soon as the individual results come in, so long as the volunteers stop by the records dept on the 1st floor and sign off, I would hope. I'd want access to serology labs, the neuropsych evaluations, and the MRIs and any other imaging results - as they become available. Potential issues involving metrics and interpretation might be mitigated this way.

 

[Hutan]

Thanks viggster.

But patients won't have access to the research test results, namely because there's no way to interpret them while the study is in progress. (E.g. Patients won't see their fMRI results.)

This is concerning. So, at what point will the fMRI results be interpretable? Perhaps only once the researchers have concocted a story about patients being overly sensitive to pain or overly concerned with self as we have seen in other fMRI studies of MUPs?

From Wikipedia:

In one real but satirical fMRI study, a dead salmon was shown pictures of humans in different emotional states. The authors provided evidence, according to two different commonly used statistical tests, of areas in the salmon's brain suggesting meaningful activity.

There's a lot of scope for making fMRI data fit a preconceived view. @Woolie, what do you think?

At some point, the results of the participants with ME will be compared to healthy participants' averages and conclusions drawn. I think individual participants should be provided with the conclusions made about them. That helps to ensure accountability. If a participant's brain function or personality is to be described in some negative way, they should have the right to know and to choose to refute that assertion.

 

[Woolie]

There's a lot of scope for making fMRI data fit a preconceived view. @Woolie, what do you think?

The researchers are right that they won't be able to give any results till they have pooled data from the whole cohort and done the appropriate analysis.

You're right that its very easy to get a false positives in neuroimaging studies, because you do so very many statistical comparisons (hundreds of thousands). Current practice is to correct for this - a bit like bonferroni. But even then, unless you have a strong hypothesis about a particular brain part/system, which is based previous research and theory in cog neuro, you're really just on a fishing expedition (excuse the pun!). Its just not possible to "read" a scan and know what mental functions are being performed. It just doesn't work like that.

There's also a lot of scope for confirmation bias, because researchers will often choose to highlight particular differences between groups that are consistent with their hypotheses (usually activity in areas that have been loosely associated with depression, pain sensation, emotion etc.), while ignoring others (those pesky differences in activity in the visual areas, for example, or the cerebellum). I have never seen a neuroimaging study that is capable of disconfirming what the authors believed in the first place - its so easy to bend the results to fit your preconceived beliefs. The FND literature is full of neuroimaging studies that confirm the "psychological" nature of the illness.

The only way neuroimaging would be interesting is if they look only at pre- vs. post- exertion differences within each group. And use broad measures, say connectivity (the efficiency in communication) involving wide networks. Within group studies are a bit less troublesome. Plus, this sort of study might have useful something to say about how the exertion impacts on brain function.

 

[viggster]

I was using fMRi as an example. The study is exploring ME/CFS with 20+ experiments, and volunteers won't have access to individual data for any of them, which is pretty standard for all medical research.

 

[duncan]

was using fMRi as an example. The study is exploring ME/CFS with 20+ experiments, and volunteers won't have access to individual data for any of them, which is pretty standard for all medical research.

Apparently not all. I was able to get my individual results as they were received for the NIH study I was enrolled in as a patient. I just had to go to "Records" and sign permission before I returned home - once Records got the data, they forwarded it to me. Included were MRI's and blood labs and LP results and neurocognitive tests. I do not know why this study should be any different.