Goal 2: Reduce Human Disease

HEALTH CARE DISPARITIES IN DIAGNOSIS AND TREATMENT OF COMMON SLEEP AND CIRCADIAN DISORDERS

There is evidence of a higher prevalence of sleep and circadian disorders in different ethnic groups. This is true for both adult and pediatric subjects. There is also evidence that minority populations in lower socioeconomic groups do not seek evaluation for sleep disorders as frequently as other segments of our population. There is also evidence that they are less adherent to treatments such as nasal CPAP for obstructive ...more »

Submitted by (@jnoel0)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Critical Challenge (CC)

Details on the impact of addressing this CQ or CC :

Sleep disorders are more common in minority populations. Moreover, these populations have higher rates of the known consequences of these disorders such as stroke, myocardial infarction, hypertension, resistant hypertension. Despite this, current population studies such as the Sleep Heart Health Study have included only a very small percentage of African Americans. The impact of this would be the following:

 

a. Elucidating the basis of barriers to case identification in these group

b. Designing specific intervention to overcome these barriers.

c. Developing methods to improve adherence to therapy in this group.

d. Removing sleep and circadian disorders as a risk factor for consequences such as stroke, cardiovascular disease and resistant hypertension in minority populations

Feasibility and challenges of addressing this CQ or CC :

There is a developing interest in this area in the field of circadian and sleep research. There is a developing knowledge base about health disparities in sleep and circadian disorders. Minority institutions such as Morehouse have developing programs in this area. We also have mobile technology that facilitates study of sleep and circadian disorders in minority populations.

Name of idea submitter and other team members who worked on this idea : Sleep Research Society

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Goal 2: Reduce Human Disease

Circadian patterns of injury/repair pathways

What is the role of clock-dependent mechanisms in cell injury/repair pathways and tissue dysfunction in heart, lung, and blood pathophysiology? How are pathways involved in disease and repair affected by aging-dependent mechanisms?

Submitted by (@nhlbiforumadministrator1)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Compelling Question (CQ)

Name of idea submitter and other team members who worked on this idea : NHLBI Staff

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Goal 2: Reduce Human Disease

DEVELOPMENT OF A PERSONALIZED APPROACH TO SLEEP AND CIRCADIAN DISORDERS

There is developing evidence of major individual differences in pathways to different common sleep disorders such as obstructive sleep apnea. Moreover, there is evidence of different clinical presentations of disease and different outcomes. For example, some subjects with obstructive sleep apnea who get excessive sleepiness while others do not. The latter are still at risk for other consequences of the disorder such ...more »

Submitted by (@jnoel0)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Critical Challenge (CC)

Details on the impact of addressing this CQ or CC :

There is a strong rationale for application of a personalized approach to sleep disorders. This requires approaching this question using multiple domains as in other areas of medicine—clinical features, physiological factors, application of the –omic approaches, genetics. The impact of this will be several:

 

a. A new way to classify sleep disorders.

b. Identification of subgroups of patients with apparently the same disorder who will have different outcomes of therapy.

c. Identification of subgroups of patients who will have different approaches to diagnosis.

d. Identification of subgroups of patients with apparently the same disorder who will have different therapeutic approaches.

Feasibility and challenges of addressing this CQ or CC :

These sleep and circadian disorders are extremely common. There is a risk infrastructure for this type of research based on the large number of accredited sleep centers in the United States that could be used for subject recruitment and who can adopt similar techniques. There is also a rich set of data obtained from sleep studies that could be used to identify new patterns that reflect different subgroups of subjects. These studies need to be based on clinical populations of patients who present with the different disorders rather than on population-based cohorts.

Name of idea submitter and other team members who worked on this idea : Sleep Research Society

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Goal 2: Reduce Human Disease

Elucidate the different causes of circadian disorders, and tailor the treatment to the cause

There are several possible physiological causes of Circadian Rhythm Sleep-Wake Disorders (CRSWDs), including lack of sensitivity to light, over-sensitivity to light, deficiencies in the ipRGC cells of the retina, lack of melatonin production, long elimination time of melatonin, long intrinsic circadian period, differences in timing of sleep relative to internal circadian rhythms, differences in tolerance to phase mismatch, ...more »

Submitted by (@peter0)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Compelling Question (CQ)

Details on the impact of addressing this CQ or CC :

By analogy, a patient may complain of abdominal pain. This could be due to infection, food poisoning, ulcers, gall bladder, cancer, etc. Imagine if we treated all these patients by removing their gall bladder. There would be some successes, and many failures. Surveys of the literature would be unable to conclude that there's a well established successful treatment. That's the state of treatment of CRSWDs today.

 

CRSWDs such as Delayed Sleep-Wake Phase Disorder and Non-24-Hour Sleep-Wake Disorder cause suffering and inability to work normal hours, and often result in otherwise productive individuals being unable to find jobs and having to seek disability support. Those who force themselves into a conventional schedule often end up with chronic health problems, resulting in further cost to themselves and to society.

Feasibility and challenges of addressing this CQ or CC :

A major challenge is to diagnose not only a CRSWD but also its underlying cause. Improved biomarkers are essential to this effort, and are the subject of other Questions/Challenges. So too are a better understanding of the effects of light and melatonin on patients with these disorders, with the differing underlying impairments studied separately. With improvements in genetic testing and analysis, and improved sensor technology and automated data analysis, we are at the threshold of being able to study these underlying causes of CRSWDs.

Name of idea submitter and other team members who worked on this idea : Peter Mansbach

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Goal 2: Reduce Human Disease

Circadian strategies to improve therapies

What circadian-based strategies (e.g. timing of medication) can be applied to improve the efficacy of treatments for heart, lung, and blood diseases (e.g. hypertension, nocturnal asthma, thrombosis, obesity/diabetes)?

Submitted by (@nhlbiforumadministrator1)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Compelling Question (CQ)

Name of idea submitter and other team members who worked on this idea : NHLBI Staff

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Goal 3: Advance Translational Research

NEW INFRASTRUCTURE FOR CLINICAL RESEARCH IN SLEEP AND CIRCADIAN DISORDERS

Much of the current clinical research on sleep and circadian research depends on cohorts designed for other purposes. While this has been helpful, such studies have limitations. These limitations are related to availability of in-depth phenotyping data and questions as to whether individuals identified in population studies are equivalent to those who present clinically with specific disorders. These concerns could ...more »

Submitted by (@jnoel0)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Critical Challenge (CC)

Details on the impact of addressing this CQ or CC :

Sleep and circadian disorders are extremely common. For many of these we know little about the natural history, whether different subgroups exist and effects of current therapies. Thus, developing specific registries for common sleep and circadian disorders would provide a basis for addressing these questions.

 

For some aspects, e.g., studies of inadequate sleep, impact of snoring and circadian disruption, would be facilitated by developing a specific sleep/circadian cohort with in-depth phenotyping. This strategy has worked extremely well in other areas, e.g., cardiovascular disease. The lack of this type of cohort for sleep and circadian disorders is a barrier to progress in this area. The high prevalence of these disorders and their known public health significance argue that development of such a cohort would be a game changer and accelerate progress in this new area of medicine.

 

Such a cohort could address several compelling questions:

 

a. What is the natural history of short sleep across the lifespan?

b. What is the impact of snoring? Does it lead, as has been proposed, to vibration injury to carotid arteries with accelerated vessel wall damage?

c. Are there different subtypes of individuals with the different sleep and circadian disorders?

d. What is the natural history of shift-workers and what types of shifts lead to increased risk for cardiovascular disease?

Feasibility and challenges of addressing this CQ or CC :

Problems with sleep and circadian rhythm and the relevant disorders are common. There are multiple accredited sleep centers for clinical purposes in the United Sates. They use common phenotyping platforms that could be the basis of some aspects of addressing this critical challenge. Moreover, most CTSA programs have a sleep study component. There are patient support groups for sleep apnea, insomnia, restless legs syndrome and narcolepsy. Thus, these groups could be marshaled to help in this effort. There is already a Sleep Research Network that was founded by the field itself. It is currently based on volunteer effort and there are no resources to support it. It could be the basis for future activities in this area.

Name of idea submitter and other team members who worked on this idea : Sleep Research Society

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Goal 1: Promote Human Health

INVESTIGATE DIFFERENTIAL VULNERABILITY TO SLEEP DEFICIENCY AND CIRCADIAN DISRUPTION

Studies in different subjects have shown that there are major individual differences in response to sleep loss and circadian disruption. Twin studies have shown that this is heritable. There needs to be an intensive effort to assess basis of these individual differences. This could include in-depth phenotyping studies, e.g., neuroimaging, genetic studies, “-omic” studies, epigenetic changes, etc.

Submitted by (@jnoel0)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Compelling Question (CQ)

Details on the impact of addressing this CQ or CC :

There are major individual differences in response to sleep loss (both acute and chronic) and to circadian disruption. This has major impact both in terms of health consequences and in safety. Some individuals are particularly vulnerable to sleep loss and hence are more likely to have adverse consequences of losing sleep—increased risk of crashes, errors by physicians, etc. They are also more likely to be affected by metabolic and other consequences if they have chronic insufficient sleep.

 

Identifying the basis of these individual differences will have several impacts:

 

1. It will provide likely targets for development of biomarkers to assess effect of sleep loss and circadian disruption.

2. It will provide tools to risk stratify individuals and to employ preventative strategies to reduce risk of major adverse consequences.

3. It will identify novel pathways that could be the target for future intervention studies.

Feasibility and challenges of addressing this CQ or CC :

These studies are highly feasible. Phenotyping and recruitment strategies to study this question have been established in many laboratories. Moreover, more laboratories are utilizing genetic, -omic approaches and epigenetic approaches that could be applied to this question. There is also a developing repertoire of neuroimaging studies that can be applied to address this question.

Name of idea submitter and other team members who worked on this idea : Sleep Research Society

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Goal 1: Promote Human Health

Do our modern "traditional" sleep schedules defy nature?

Here's an interesting article which shows that the modern tradition of eight hours of unbroken sleep might actually be unnatural, and quite different from what our ancestors typically did: http://www.bbc.com/news/magazine-16964783 So, maybe the majority of our modern societies (even the people without recognized sleep disorders) are unwisely fighting against biology? Perhaps a lot of people's health issues, such as ...more »

Submitted by (@apollia112)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Compelling Question (CQ)

Details on the impact of addressing this CQ or CC :

See comments

Feasibility and challenges of addressing this CQ or CC :

See comments

Name of idea submitter and other team members who worked on this idea : Apollia

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Goal 2: Reduce Human Disease

Understanding of chronobiological systems

We know that all life functions are based on circadian and other rhythms; chronobiological systems are interdependent in intricate ways. Disturbances and disorders in one part of a system may affect other vital systems in unexpected but far-reaching ways. Many aspects of circadian rhythms and sleep-wake regulation in normal, healthy humans have been charted. Much of the knowledge thus gained is assumed to be valid also ...more »

Submitted by (@nma120)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Critical Challenge (CC)

Details on the impact of addressing this CQ or CC :

As research on the extrinsic Shift Work Disorder shows, disturbances of the normal person’s sleep-wake cycle have consequences. These may include excessive daytime sleepiness, increased risk of traffic and other accidents, dysregulation of metabolic and other systems, obesity, increased risk of cancer, cardiovascular diseases, mood disorders and other diseases. Normal people trying to function on an abnormal schedule may develop conditions that lead to disability or death. Intrinsic CSWD patients suffer many of the same conditions as well as others.

 

These patients desperately need answers: Why am I like this, Do I dare have children, Will it get worse as I age, Can anything be done in addition to light boxes, scototherapy and melatonin, What is really the best timing in use of these treatments, Will I get disability?

 

Research on these patients will likely lead to discoveries that could be the target for future studies, thus impacting the modern fields of sleep and circadian rhythms research.

Feasibility and challenges of addressing this CQ or CC :

The intrinsic CSWDs are:

 

1) Lifelong DSWPD, delayed sleep-wake phase disorder

2) Adolescent DSWPD

3) ASWPD, advanced sleep-wake phase disorder

4) ISWRD, irregular sleep-wake rhythm disorder

5) Blind Non-24, N24SWRD, non-24-hour sleep-wake rhythm disorder in the blind

6) Sighted Non-24, N24SWRD in the non-blind.

 

I have listed 6 disorders; the usual number is 4. The first 2 on my list are usually combined, as are the last 2.

 

Some of the challenges, for different age groups and degrees of severity, are to:

--Find the causes of the disorders that are not yet explained

--Examine genetics and heritability

--Differentiate teens’ DSWPD as adolescent or persistent type

--Discover why adult DSWPD often precedes the development of Non-24 in sighted people

--Validate the use of light therapy, dark therapy and melatonin, including detailed recommendations for the timing and dosage of each of them

--Find other, more reliable, treatments

--Develop simple tests for determining persistent internal circadian desynchronization in an individual.

 

 

Some of the disorders have been explained, in whole or in part. There is great need for work with, at least, the following groups of patients:

-Adult DSWPS

-Pre-puberty children w/ DSWPS

-Adult sighted N24

-Pre-puberty sighted children w/ Non-24

 

Of these, adults with DSWPD are, of course, the most numerous. Research on that disorder may lead to results of interest for N24, these disorders being closely related.

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Goal 1: Promote Human Health

DESIGN AND EVALUATE INTERVENTION STRATEGIES TO IMPROVE SLEEP HEALTH AND CIRCADIAN DISRUPTION

Data indicate the association between short sleep and circadian disruption on a number of adverse outcomes such as cardiovascular disease, metabolic disorders, hypertension, etc. There is a need to move beyond association to interventions that can be shown to improve sleep duration and circadian disruption.

Submitted by (@jnoel0)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Compelling Question (CQ)

Details on the impact of addressing this CQ or CC :

As described, we need to move beyond association to intervention. We have developing mobile technologies to assess outcomes in subjects living in their normal circumstances. The issue is what interventions can be applied and be shown to work to address both sleep length and circadian timing of sleep. There is a need to stimulate research to assess different potential interventions to see which are the most effective.

 

The impact of this will be invaluable. We should be able to improve sleep and circadian health in the US population and thereby modifying this risk factor for development of chronic diseases.

Feasibility and challenges of addressing this CQ or CC :

We have the relevant tools to do this. There are millions of Americans with short sleep and millions of Americans who have misplaced sleep in relation to their normal circadian rhythms. Thus, there is no shortage of subjects to recruit for this type of research. There is now a developing body of knowledge about techniques that can be applied to modifying behavior in other areas—weight loss, stopping smoking, etc. These techniques could be the basis of new interventions to improve sleep health.

Name of idea submitter and other team members who worked on this idea : Sleep Research Society

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Goal 3: Advance Translational Research

DEVELOPMENT OF BIOMARKERS FOR SLEEP INSUFFICIENCY, CIRCADIAN DISRUPTION AND SLEEP DISORDERS

There is an urgent need to develop quantifiable biomarkers for acute sleep loss, chronic sleep insufficiency, circadian disruption and sleep disorders such as obstructive sleep apnea. These problems are highly prevalent but currently we do not have biomarkers to use for case identification, prognosis, or assessing response to therapy. There are currently small studies that indicate the feasibility. A recent workshop ...more »

Submitted by (@jnoel0)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Critical Challenge (CC)

Details on the impact of addressing this CQ or CC :

The following will be the impact of addressing this critical challenge:

 

1. Having an assessment that can be used following a crash to assess the level of sleep loss of the driver.

2. Having a method to assess chronic sleep insufficiency as a potential pathogenetic process in patients with cardiovascular disease, hypertension, etc.

3. Having a method to estimate circadian phase so that in patients with chronic insomnia one can identify individuals with delayed sleep phase.

4. Having a technique to establish magnitude of circadian disruption to assess its role in pathogenesis of diseases such as cardiovascular disease.

5. Add a molecular biomarker to other techniques to screen for obstructive sleep apnea in high risk populations such as obese commercial drivers.

6. Utilize a biomarker signature to identify who with obstructive sleep apnea will be particularly at risk for downstream consequences such as cardiovascular disease.

7. Develop the equivalent of HbA1C to assess therapeutic response to CPAP

Feasibility and challenges of addressing this CQ or CC :

The first challenge is to identify a signature for each of these use cases. This will require initial studies in a small number of well phenotyped subjects with all the “-omic” techniques. Thereafter, these multiple cohorts, already available with blood samples, etc. and relative phenotype can be used for validation purposes.

Name of idea submitter and other team members who worked on this idea : Sleep Research Society

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