NIH Program Announcement For CFS Lists Areas of Research NIH is interested in

[Cort]

http://grants.nih.gov/grants/guide/pa-files/PA-08-246.html#SectionI

"Mangan's imprint is definitely on this. Check out the inclusion of ME...They also emphasis microbrial infections...At one point in the last decade the NIH basically said we're not studying pathogens anymore.

There is a definite focus on intersystemic signaling - how the different systems of the body talk to each other. They have focused on that for quite a while. I like his idea to try and ally ME/CFS with other disorders - although we'll see how that turns out. There is also a focus on gender; I think its a good idea to look at why women are more like to get ME/CFS and FM and,,,.,..a focus on subsets,

I've never seen the desire to control for phase of the menstrual cycle....I imagine this has something to do with the 'subtle perturbations' mentioned and the fear that the menstrual cycle will swamp them....it seems a bit much, though to ask a researcher to do that....that's alot of work to make sure your participants are 'in phase'.

I like this because it gets us an entree into other disorders funding

Never seen 'clock related genes' before -

Conduct genetic epidemiologic and cellular biologic studies investigating whether polymorphisms in clock-related genes a

Conduct case-control comparisons of CFS with syndromes such as fibromyalgia, interstitial cystitis, chronic pelvic pain syndrome, irritable bowel syndrome and other multisystemic illnesses that have similar or overlapping symptomatology

This is one of my favorites

Study the role of neuro-cardiovascular regulation in the loss of the normal control of blood pressure, heart rate and contractility in CFS patients

It like all federal announcements of this type is very broad and there will be things in here that are objectionable to some; that is expected and there's alot of good in here.

The proof is in the pudding and what kind of studies they end up funding.

1. Research Objectives

This Funding Opportunity Announcement (FOA) issued by the Office of Research on Women's Health (ORWH) and co-sponsoring Institutes and Centers (ICs) of the National Institutes of Health (NIH) encourages investigator(s)-initiated applications that propose to examine the etiology, diagnosis, pathophysiology, and treatment of chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME/CFS), in diverse groups and across the lifespan.

Applications that address gaps in the understanding of the environmental and biological risk factors, the determinants of heterogeneity among patient populations, the common mechanisms influencing the multiple body systems that are affected in CFS are encouraged. The NIH is particularly interested in funding interdisciplinary research that will enhance our knowledge of the disease process and provide evidence based solutions to improve the diagnosis, treatment, and quality of life of all persons with CFS. This interdisciplinary research may include the building of scientific teams to study and develop biomarkers, innovative treatment modalities, and/or the modifiable risk and protective processes specifically targeted by preventive and/or treatment interventions.

CFS (CFS/ME) is a debilitating and complex syndrome that involves multiple body systems. It is characterized by profound fatigue that is not improved by bed rest and may be exacerbated or re-kindled by physical or mental activity. Persons with CFS most often function at substantially lower levels of activity from their pre-onset capacities. In addition to these defining characteristics, a diverse array of other symptoms is associated with CFS. These symptoms include cognitive deficits, impaired sleep, myalgia, arthralgia, headache, gastrointestinal symptoms, and tender lymph nodes. Neither a specific cause(s) nor any specific diagnostic test(s) have been identified for this illness.

The range of symptoms, however, suggests that there may be subtle perturbations in at least two systems of the body that are important for homeostatic regulation and in the multiple physiological pathways through which these systems communicate. These dysregulations may be triggered by diverse causes such as infection, stress, brain structure abnormalities, hormone levels, proinflammatory cytokines, etc. Evidence is needed to detail the immune mechanisms and/or mechanisms of microbial pathogenesis involved in CFS.

Epidemiological evidence also requires further study. Existing data suggest that approximately one million people in the United States are afflicted. CFS is said to occur more frequently among women than men and among white Americans than in Americans of other racial/ethnic groups. More recent studies narrow the gap between the sexes, as well as among racial/ethnic population subgroups. In addition, the prevalence of CFS in children remains in dispute.

The role of dietary factors, background diets, and body compositions in study participants and persons with CFS also remains to be studied, along with differences according to race and gender across the lifespan.

Recent epidemiological data reveal CFS, as well as other disorders that share pain as a common symptom, is often associated with chronic urologic pelvic pain syndromes. This relationship remains to be further elucidated through epidemiological and basic-science research.

Detection and treatment of CSF also merit further study. Promising research to date has focused on identification of biomarkers for diagnosis of CSF; nonetheless, more work is needed for a clinically applicable detection method. Studies of innovative treatment modalities and their relationship(s) to pathophysiology of CFS and to co-morbid conditions are also needed.

Innovative, well designed studies are needed to provide a better understanding of CFS, prevalence, pathogenesis, and pathophysiology, with the goal of developing improved diagnostic and intervention strategies The heterogeneity of the CFS population should be recognized in both basic, translational and clinical research; thus, sex, age/developmental stage, racial and ethnic variations should be considered along with any subtyping of CFS in the study designs.

In addition studies using girls and women of reproductive age should control for phase of the menstrual cycle. This FOA encourages the integration of basic research with clinical observations in forming study hypotheses. The multisystemic nature of the disorder will benefit from a collaborative multidisciplinary (across scientific disciplines) team approach that will lead to the interdisciplinary solutions necessary to provide a foundation for understanding, diagnosing and treating this complex illness.

Applicants are encouraged to review the information on the CFSWG Web site (http://orwh.od.nih.gov/cfs.html) as well as recommendations from an NIH-sponsored CFS science summit held in October 2000 at Arlington, VA. This document may be found at http://orwh.od.nih.gov/cfs/cfsWkshopSummary_6-03.pdf. They also are encouraged to review the summary of the scientific workshop: Neuroimmune mechanisms and chronic fatigue syndrome: understanding central mechanisms, which may be found at http://www4.od.nih.gov/orwh/cfs-newhome.html. Applicants also are referred to the Agenda for Research on Women's Health for the 21st Century, volume 2" (NIH Publication No 99-4386,http://orwh.od.nih.gov/pubs/agenda_book_2.pdf), as well as Exploring the Biological Contributions to Human Health. Does Sex Matter" (National Academy Press, Washington DC,http://www.nap.edu/), to ensure appropriateness to all aims of this FOA.
Areas of interest where scientific opportunities exist to meet the objectives of this funding opportunity cut across many disciplines. Applications within, but not limited to the following, may propose to:


Epidemiology

• Explore whether pathogenesis and pathophysiology differ relative to age, sex, developmental period, racial/ethnic background, and co-morbid conditions
• Compare the diagnostic criteria and symptomatology of CFS in children and adolescents with those of adults
• Describe the epidemiology of CFS in older adults and explore the relationship of CFS to general complaints of fatigue and exhaustion in the elderly.
• Conduct case-control comparisons of CFS with syndromes such as fibromyalgia, interstitial cystitis, chronic pelvic pain syndrome, irritable bowel syndrome and other multisystemic illnesses that have similar or overlapping symptomatology
• Conduct genetic epidemiologic and cellular biologic studies investigating whether polymorphisms in clock-related genes alters cellular function in peripheral cardiovascular tissue or mediates abnormalities in peripheral endocrine function that are characteristic of the autonomic nervous system dysfunction associated with CFS.

Diagnosis

• Develop novel and objective biological markers for the diagnosis of CFS
• Develop and validate techniques for linking biomarkers to behavioral responses associated with CFS
• Develop/refine objective measures for fatigue or sleepiness and severity of associated sleep disturbances
• Develop/refine technologies to improve the identification and measurement of precipitating factors
• Conduct longitudinal studies and studies with multiple sampling points to capture the progression of CFS symptomatology
• Explore the role of neuroimaging modalities in the diagnosis, treatment and progression of CFS

Risk Factors

• Identify environmental, including dietary, and other precipitants and geographic correlates of CFS
• Conduct animal studies to elucidate the effects of environmental exposures, including endocrine disrupters, on the stress response contributing to CFS.
• Identify the biological antecedent or triggering events that precipitate CFS
• Explore multi-systemic factors as precipitants to CFS symptoms
• Conduct population studies to elucidate potential genetic risk factors
• Examine the role of genetic polymorphisms in the pathogenesis and diagnosis of CFS
• Explore the relationship of co-morbid conditions and CFS
• Explore the potential relationship of CFS with other chronic pain syndromes

Neurological and Behavioral Factors

• Study the nature of psychiatric comorbidity in CFS patients
• Elucidate the factors/mechanisms mediating common symptomatology in CFS: cognitive deficits, chronic pain, and/or inability to sustain physical exertion
• Elucidate the factors/mechanisms involved in altered sleep states, disrupted circadian regulation, or other causes of impaired or ineffective sleep
• Study the relationships between cognitive deficits and sleep disturbances or sleep disorders
• Investigate long-term cognitive, psychosocial, and physical health outcomes in children and adolescents with CFS
• Investigate the relationships of fatigue and CFS to other comorbid medical conditions or disabilities common in older patients, and/or to the drug effects and interactions of medications used to treat these conditions

Physiologic Interactions

• Study the role of neuroendocrine and neuroimmune functions in CFS pathogenesis and pathophysiology
• Study the role of neuro-cardiovascular regulation in the loss of the normal control of blood pressure, heart rate and contractility in CFS patients
• Study the action of mediators (i.e., cytokines, chemokines) on the multiple, interacting, feedback-controlled systems that are dysregulated in CFS (pathogenesis and pathophysiology)
• Study the mechanisms and consequences of dysregulation in the major physiologic control systems to better understand the multi-system symptoms among CFS patients
• Study the role of oxidative stress in the pathogenesis of and marginal nutritional deficiencies in the etiology of CFS.
• Explore the relationships of fatigue and CFS to biochemical mediators associated with frailty in the elderly, such as pro-inflammatory cytokines.

Treatment and Quality of Life

• Conduct clinical trials in CFS patients to determine the efficacy of reliable and valid strategies that are used to improve quality of life in other chronic diseases
• Conduct definitive trials to determine the effectiveness of currently prescribed pharmacologic, behavioral and other treatments used in CFS
• Develop and test new pharmacologic and nonpharmacologic strategies for ameliorating symptoms that impair quality of life in patients with CFS
• Study perceptions, attitudes, and behaviors that influence both the course of CFS and the quality of care provided to CFS patients
• Examine the role of self-medication with alcohol, illicit drugs, and/or prescription drugs in CFS patients.
• Examine the use and establish the efficacy and safety of dietary supplements in the treatment of CFS
• Develop and test the efficacy of interventions to ameliorate fatigue and CFS that are targeted at the specific needs of the elderly

Methodological Considerations

• Multidisciplinary studies and collaboration among investigators with expertise in appropriate disciplines are encouraged. When investigators are at different institutions, individual R01 applications may include consortium arrangements.
• Collaborative arrangements with ongoing studies that provide patient populations, specimens, and data are encouraged. Such arrangements should be clearly delineated in the application.
• Investigators are encouraged to use the CFS case definition as presented in Fukuda, et al. Annals of Internal Medicine 1994; 121: 953-9. If other case definitions are proposed, they should be clearly defined and the rationale for the alternative choice clearly delineated. Similar care should be given to definition of sub-groupings for CFS patients, if you choose to consider them.
• Methods and procedures used in selecting patients or their specimens should be precisely defined and described in detail. Care should be given to the criteria used for case definition and the manner in which the criteria are applied. Similar care should be given to descriptions of procedures and methods for enrolling subjects in comparison groups.

Applications for small studies that explore new ideas or investigative techniques are also encouraged and could provide the basis for submission of a subsequent larger grant application. In particular, studies that examine and develop biomarkers and innovative treatments are encouraged. See the parallel R21 PA-08-247 FOA.
See Section VIII, Other Information - Required Federal Citations, for policies related to this announcement

 

[Hope123]

Cort, is this really new or revised compared to the old PA? I didn't save the old PA but it doesn't look new to me on skimming it. The same deadlines still apply -- the PA expires 9/ 2011 and I don't know if it will be renewed yet.

 

[Dolphin]

Cort, is this really new or revised compared to the old PA? I didn't save the old PA but it doesn't look new to me on skimming it. The same deadlines still apply -- the PA expires 9/ 2011 and I don't know if it will be renewed yet.

I would be interested in this also. Here's a link to one Release/Posted Date: August 21, 2008 http://grants.nih.gov/grants/guide/pa-files/PA-08-246.html . It mentions "also known as myalgic encephalomyelitis (ME/CFS)". Cort may have assumed it was new because of that mention (it had got me thinking) but I'm not sure now. I don't have the time/energy to look into it in more detail.

 

[svetoslav80]

Interesting, I have chronic pelvic pain syndrome.