The Sleep Disorders Research Advisory Board convened virtually on Thursday, December 5, 2024, from 11:00am ET to 5:00pm ET. The purpose of this meeting was to update the Advisory Board and public stakeholders on the progress of sleep and circadian research activities across NIH, and on the activities of Federal stakeholders and interested organizations. Dr. Esra Tasali presided over the meeting as Chair and the minutes appear below.

MEETING SUMMARY

BOARD MEMBERS PRESENT

Dr. Esra Tasali, Chair 
Dr. Josiane Broussard
Dr. Paula Desplats
Dr. Jeffery Durmer 
Dr. Erik Herzog 
Dr. Dayna Johnson
Dr. Shaun Purcell
Dr. Alberto Ramos 
Ms. Alexandra Wharton

BOARD MEMBERS ABSENT
None

EX OFFICIO MEMBERS PRESENT
Dr. Marishka Brown, Executive Secretary
Dr. Yejun (Janet) He
Dr. Amanda Hunt

FEDERAL EMPLOYEES
Twenty-two Federal employes attended the meeting.

MEMBERS OF THE PUBLIC
Forty-nine members of the public attended the meeting (including researchers, clinicians, patients, and other stakeholders).

CALL TO ORDER
Marishka Brown, Ph.D., SDRAB Executive Secretary

• The executive secretary called the meeting to order at 11:00 AM ET as announced in the Federal Notice [89 FR 83026] on June 20, 2024. The meeting was fully open to the public in accordance with the provisions set forth in sections 552b(c)(4) and 552b(c)(6), Title 5, U.S. Code and Section 10(d) of the Federal Advisory Committee Act.
• Board members were reminded they are required to absent themselves if their presence constitutes or appears to constitute conflict of interest.
• Dr. Brown introduced the chair of SDRAB, Dr. Esra Tasali.
• The Chair welcomed everyone and SDRAB members introduced themselves.

LEADERSHIP LENS: NIH Office of Dietary Supplements (ODS)
Stefan Pasiakos, Ph.D., Director, ODS, NIH

• Overview of the Office of Dietary Supplements ODS: established in 1995 and has grown to cover expertise spanning nutrition, physiology, chemistry, natural products, pharmacology, epidemiology, public health, food security, climate science, nursing communications, and administration and management. The Office does not have direct funding authority but does co-fund a number of research studies, including several sleep-related projects and uses its platform as a coordinating office
• Introduced Strategic Plan for 2025-2029 which serves as a blueprint for a coordinated dietary supplement research agenda at NIH to empower collaboration to identify knowledge gaps of shared and timely interest across NIH and other Federal agencies.
• Presented the role of nutrition and dietary supplements on sleep:
  • Research has made it increasingly clear there is a strong bidirectional relationship between sleep and diet.
  • The most heavily studied and used dietary supplement in the context of sleep is melatonin use, which has increased in adults, children and adolescents. Research challenges and public health concerns associated with melatonin, such as supplement formulation and quantity ingested according to a 2023 study. Melatonin might be contributing to negative health consequences and concerns of overdosing in young populations
• The Council for Responsible Nutrition issued voluntary guidelines for the formulation, labelling, and packaging of melatonin-containing dietary supplements for sleep support.
• Non-prescription approaches for improving sleep are widely used (Sleep Disorders and Complementary Health Approaches)
• Dietary Supplement Label Database (DSLD) catalogs over 200,000 dietary supplement products sold in the U.S.  There are 3,300 labels in the DSLD that use the word “sleep”
• Highlighted gaps and opportunities at the intersection of dietary supplements and sleep:
  • Novel approaches to address issues of insufficient sleep, including discovery of new targets
  • Prevalence of use in generally healthy people of different non-prescription approaches across the lifespan and in diverse population subgroups
  • Understanding the supplements and other ingested approaches used that have not been commonly described in the English language research literature
  • Research that supports obtaining data on safety and efficacy of non-prescription ingested approaches

SCIENTIFIC FOCUS PRESENTATION – Light, Circadian Rhythms, and Human Health
Helen Burgess, Ph.D., Professor, Department of Psychiatry
Co-Director, Sleep and Circadian Research Laboratory
University of Michigan, Ann Arbor

• Introduced circadian and non-circadian effects of light on human health. The circadian system has a profound effect on our physiology because nearly every cell in the body express a circadian rhythm. In humans the circadian period or the time it takes the circadian system to complete a cycle on average is slightly greater than 24hours
• The circadian system has 3 components:
  • The SCN acts as a central clock orchestrating daily cycles of sleep, hormone release, and other physiological processes.
  • Peripheral rhythms are controlled by the SCN but can also feedback to influence the timing of the central clock
  • Zeitgebers “time givers” are external stimuli, such as light, that can shift the timing of the SCN.
• Dr. Burgess then described work she is doing at the University of Michigan in bipolar disorder with a focus on circadian rhythms in the Prechter Longitudinal Study of Bipolar Disorder
• She is also collaborating to study the effects of morning light treatment on chronic pain, particularly fibromyalgia
• She ended her presentation with a discussion on morning light treatments resulting in a phase advance may be a potential pathway to reduce pain.

DIRECTOR’S REPORT - National Center On Sleep Disorders Research (NCSDR)
Marishka Brown, Ph.D., Director, NCSDR

• SDRAB is an NIH Program Advisory Committee that provides advise on specific research programs, future research needs, and opportunities
• Reviewed sleep and circadian research grants and funding levels across NIH, metrics that show robust support for sleep and circadian research
• All activities align with the NIH-Wide Sleep Research Plan through collaboration with the NIH Sleep Research Coordinating Committee
• Research promotion activities are also aligned with the NIH-Wide Strategic Plan and NHLBI Strategic Vision, which is currently undergoing a refresh.
• 2018 Conference: Sleep and the Health of Women hosted by NHLBI in collaboration with 11 other ICOs including the NIH Office of Research on Women’s Health (ORWH), and the HHS Office on Women’s Health identified unique challenges for women at different life stages
  • Extent to which sex impacts sleep and sleep pathophysiology across the lifespan
  • Contributions of sleep deficiency to health disparities
  • Under-recognition and misdiagnosis of sleep disorders in women and girls
• Additional NIH presentations, conferences, and workshops on sleep and the health of women, including most recently a 2-day workshop on Heterogeneity and Sex Differences in Obstructive Sleep Apnea (Day 1 video, Day 2 video) and Notice of Special Interest: Women’s Health Research (NOT-OD-24-079)
• Dr. Brown highlighted several other funding opportunities related to sleep but reminded the audience that all investigator-initiated mechanisms are open to sleep and circadian biology research projects.
• Reminder to contact the Program Official to discuss their application prior to submission.
• Major NIH initiatives involving NCSDR:
  • REsearching COVID to Enhance Recovery Initiative (RECOVER)
  • INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE) Project (INCLUDE)
  • Helping to End Addiction Long-term Initiative (HEAL)

CENTER FOR SCIENTIFIC REVIEW (CSR) PRESENTATION – Simplified Peer Review Process 
Valerie Durrant, Ph.D., Director, Division of AIDS, Behavioral and Population Science 
Brittany Mason-Mah, Ph.D., Scientific Review Officer, Mechanisms of Emotion, Stress and Health (MESH) program

• Center for Scientific Review (CSR) Role:
  • Manages peer review for all 27 NIH funding ICs and the Office of the Director
  • Two-stage review process
    • Stage 1: study section or Special Emphasis Panel (SEP) evaluate scientific and technical merit of grant applications
    • Stage 2: IC Advisory Council review outcomes, advise on programmatic priorities
• Snapshot of CSR FY24 numbers:
  • Reviewed 66,700 (77%) of all NIH applications
  • 255 Scientific Review Officers (SROs), 19,000 reviewers, 1,200 review meetings (550 standing study sections; 650 SEPs)
  • 164 special initiatives reviewed
• NEW Simplified Review Framework effective for most grant applications submitted on or after January 25, 2025 (does not apply to small business SBIR/STTR). The motivation for the SRF was:
  • The motivation for the new framework is to streamline overly complex review criteria and reduce undue influence of reputation
  • 3 Core Factors:
    • Factor 1: Importance of Research (Significance, Innovation), scored 1-9
    • Factor 2: Rigor and Feasibility (Approach), scored 1-9,
    • Factor 3: Expertise and Resources (Investigators, Environment), not scored
  • Overall Impact score remains; most “Additional Review Considerations” removed
  • NIH fellowship application and review process applies to all fellowship applications (F applications only) submitted for due dates after January 25, 2025. Applications shortened, structured, more focused on training quality (grades no longer required/allowed), and review is limited to 3 criteria:
  • Candidate’s Preparedness and Potential
  • Research and Training Plan
  • Commitment to the Candidate
• For more information about these changes, please see the following webpages
  • Simplifying Review of Research Project Grant Applications
  • Revisions to the NIH Fellowship Application and Review Process
• Applicants/reviewers can report concerns to reportbias@csr.nih.gov

STAKEHOLDER GROUP UPDATE – Society for Biological Rhythms (SRBR)  
John Hogenesch, Ph.D., Professor of Pediatrics, Cincinnati Children’s Hospital Medical Center
Current President, SRBR

• The Mission of the Society for Biological Rhythms (SRBR)  is to promote research and education in biological rhythms, raise awareness, and advocate for policies that improve health by integrating circadian principles. .
• SRBR Activities:
  • Biennial Conference – largest in the field; historically focused on basic mechanisms, now shifting toward clinical translation (4 members awarded Nobel Prizes).
  • Journal of Biological Rhythms – supported by SRBR.
  • Education & Training – programs for students and trainees.
  • Advocacy & Outreach – website, social media, white papers (light needs, eating timing, medicine timing, school start times), outreach fellowships, collaboration with the Sleep Research Society (SRS)
• SRBR alignment with the NIH Sleep Research Plan
  • Support mechanistic studies of circadian clocks.
  • Improve sleep/circadian rhythms and test links to disease.
  • Translate circadian biology into clinical practice.
  • Develop measures of sleep quality & circadian misalignment.
  • Promote multi-center trials, field-condition studies, and outreach on work/school schedules.
• Discussion of important next steps for the field
  • Standardizing methodology for circadian research across circadian/sleep societies worldwide – e.g. actigraphy, molecular diagnostics
  • NIH institute collaboration on support of circadian grants (including R13s)
  • Fundraising to support trainee programs
  • Education on circadian medicine as distinct from sleep medicine

FEDERAL STAKEHOLDER UPDATE – Department of Defense  
Michael Goodson, Ph.D., Research Biologist, U.S. Air Force Research Laboratory
Jason Soares, U.S. Army DEVCOM Soldier Center

• Presenter Disclaimer:

The views expressed in this presentation are those of the authors and do not reflect official policy of the Department of the Army, Department of the Air Force, Department of Defense, or the U.S. Government.

• Humans are ~40–50% human cells and ~50–60% microbial cells; microbes provide ~300x more genes than the human genome, with major influence on physiology (mood, behavior, pain tolerance). Deployment stressors (time zones, climates, food, physical demands, high-stakes environments) can disrupt the microbiome, leading to cognitive decline and health risks.
  • Interventions under study: prebiotics, probiotics, symbiotics, and smart biotics (engineered microbes).
  • Partnerships: Air Force Research Labs (AFRL), academia, and industry.
• Biotechnology Grand Challenge (AFRL, 2020)
  • Goal: Microbial intervention for sustaining performance during multi-day sub-optimal sleep.
  • Winning team (MIT, Tufts, Synlogic Therapeutics): engineered microbes to produce guanidine acetic acid (GAA) → precursor to creatine. Advantage over direct creatine ingestion: sustained tissue levels, lower weight burden in field, reduced dosing needs.
• Prototype & Human Studies
  • 2022: Engineered probiotic prototype completed in lab.
  • 2023–2026: Human intervention studies in simulated operational environments.
  • Post-2026: Transition to operational battlefield studies.
• Planned engineered probiotic aims to improve cognitive fatigue resiliency during sleep deprivation, with outcomes measured via performance on operationally relevant tasks

NIH-WIDE SLEEP RESEARCH COORDINATING COMMITTEE (SRCC) PRESENTATION – National Institute of General Medical Sciences (NIGMS)
Michael Sesma, Ph.D., Chief, Postdoctoral Training Branch, Division of Training, Workforce Development and Diversity (TWD)
Lameese Akacem, Ph.D., Program Director, TWD

• National Institute of General Medical Sciences (NIGMS) mission is to support basic research that increases our understanding of biological processes and lays the foundation for advances in disease diagnosis, treatment, and prevention
  • Research spans how living systems work at a range of levels—from molecules and cells to tissues and organs—in research organisms, humans, and population
  • Strong focus on training of the next generation of scientists, broadening participation in the scientific workforce, and developing research capacity throughout the country
• Maximizing Investigators’ Research Award (MIRA R35)
  • Goal:  Provides stable, flexible funding to increase productivity and support broad investigator-driven research.
  • Enables pursuit of new research directions as opportunities arise
• Training the next generation of scientists
  • Institutional programs and individual fellowships
  • Support at key transition points (e.g. undergraduate to graduate, graduate to post-doc, postdoc to faculty)
  • NIGMS support to broaden participation and strengthen the biomedical workforce
• Circadian Biology research priorities at NIGMS
  • Supports work on the genetic, molecular, and/or genomic characterization of circadian rhythms and regulatory processes associated with circadian clock elements, sleep, and related behavioral and physiological phenomena
  • Studies in this portfolio reveal different aspects of the clock functioning, including clock mechanism and regulatory processes that are associated with the clock
  • Questions to be explored are primary versus the research organism to be used to explore the questions because the basic regulatory and timekeeping mechanisms of the clock appear to be similar across different organisms
  • Emphasis in non-human systems including invertebrates, plants, fungi, and bacteria
• The bulk of the work done by the three scientists (Jeffrey Hall, Michale Rosbash, and Michael Young) awarded the 2017 Nobel Prize in Physiology or Medicine for their discoveries of molecular mechanisms controlling circadian rhythms was funded by NIGMS
• NIGMS circadian biology research highlights:
  • A Global Transcriptional Atlas of the Effect of Acute Sleep Deprivation in the Mouse Frontal Cortex – grantee Lucia Peixoto, Washington State University
  • A Novel Home-Based Study of Circadian Rhythms: Design, Rationale, and Methods for the Circadia Study – grantee Jacqueline Lane, Brigham and Women’s Hospital
  • Bacteria Can Anticipate the Seasons: Photoperiodism in Cyanobacteria – grantee Carl Johnson, Vanderbilt University
  • Chronic Sleep Loss Disrupts Rhythmic Gene Expression in Drosophila – grantee Michael Young, Rockefeller University
  • A Circadian Behavioral Analysis Suite for Real-Time Classification of Daily Rhythms in Complex Behaviors – grantee Jeff Jones, Texas A&M University
  • Clock-Dependent Chromatin Accessibility Rhythms Regulate Circadian Transcription – grantee Swathi Yadlapalli, University of Michigan

SDRAB MEMBER DISCUSSION – Part 1
Lead by Dr. Esra Tasali

• The Board raised concerns about the increase in melatonin use since 2013 and the variability in supplement content. They noted that researchers often do not know the actual composition of the supplements being tested, which complicates findings on efficacy and dosing. A best practice would be to analytically test supplements used in studies. Since ODS is not a funding agency, its influence comes from collaborations with NIH ICs that do fund sleep research.
• SDRAB acknowledged the access and financial barriers to high quality foods that underserved populations face, in addition to the financial burden of taking dietary supplements for sleep aids. They noted this is another reason the efficacy of these supplements needs to be accurately tested.
• SDRAB also noted the need to consider when dietary supplements are taken and their potential influence on the circadian system. Another best practice for researchers would be to consider time as a biological variable in much the same way the sex is considered as a biological variable when studying the impact of supplements on the body.
• The Board commented that reallocation modeling or compositional modeling where you consider the 24 hour period and how it is being spent within specific activities is also being utilized more in research.
• Since one of the aims of the Circadia Study is to create a toolkit for at-home circadian rhythm assessment through the use of surveys, tests, and collection kits, the Board wondered if there were an opportunity to include wearables in the toolkit, to enhance the data being collected by adding objectives measures of activity, heart rate, and temperature.
• Considering the Goodson/Soares talk, the Board wondered if it there might be value in examining how the microbes in the fecal samples being collected in Dr. Burgess’ study might be affected by the light treatments. Microbes in the human gut have circadian rhythms that are aligned with the host and while the microbial content might not change in response to treatment, their metabolic potential might.
• Dr. Burgess commented it would be interesting to study the effects of light treatments and sleep stabilization on systemic inflammation and local inflammation in the gut.
• The Board noted that prebiotics, probiotics, and symbiotics are widely available over the counter and increasingly used to enhance sleep and other health outcomes. They stressed the need for more mechanistic research to understand gut-brain and gut-sleep relationships, as well as the role of the microbiome in health more broadly.

NIH-WIDE PROGRAMMATIC UPDATES – RECOVER
Susan Redline, M.D., M.P.H., Professor of Sleep Medicine, Brigham and Women’s Hospital Professor of Epidemiology, Harvard University School of Public Health
Co-lead of the RECOVER-SLEEP clinical trials

• Dr. Redline, a member of the RECOVER Initiative Clinical Trial Steering Committee and Co-Chair of the Sleep Working Group, highlighted the importance of incorporating sleep into both RECOVER’s longitudinal cohort and clinical trials. She also directs the RECOVER Sleep Reading Centers.
• Relationship between sleep and COVID-19
  • Healthy sleep and circadian rhythms are critical for immunity, mental and physical health, longevity, and well-being—core outcomes for long-COVID patients.
  • Pre-existing sleep disorders (e.g., sleep apnea) are linked with higher COVID-19 mortality and hospitalization risk.
  • COVID-related systemic and neural inflammation may trigger or worsen long-term sleep disorders (insomnia, hypersomnia, apnea, restless leg syndrome, irregular patterns, narcolepsy, REM behavioral disorder).
  • These disorders can worsen long-COVID outcomes but may also represent intervention targets.
• RECOVER Adult Cohort Objectives
  • Define and measure long-COVID prevalence.
  • Characterize symptoms, organ dysfunction, and distinct phenotypes.
  • Identify demographic, social, and clinical risk factors.
  • Investigate biological mechanisms of PASC (post-acute sequelae of COVID-19).
• Sleep data collected across RECOVER Adult Cohort
  • ~1,800 home sleep apnea tests from 64 sites.
    • 20% prevalence of obstructive sleep apnea (OSA).
    • 14% of studies triggered urgent hypoxia alerts (<88% oxygen saturation overnight).
  • ~250 facility-based polysomnograms (PSGs) submitted from 24 sites.
    • 40% prevalence of moderate–severe OSA.
    • 24% prevalence of elevated periodic limb movements.

4% showed abnormal chin muscle tone.

• Much of the RECOVER analysis effort has been focused on trying to better understand clusters of symptoms, how they may respond to therapy, and on predicting persistence and mechanisms

PUBLIC QUESTIONS/COMMENTS

• There were no additional questions or comments from the public that had not already been addressed in earlier discussions.

SDRAB MEMBER DISCUSSION – Part 2
Lead by Dr. Esra Tasali

• Dr. Brown started the discussion by encouraging the Board to recognize the theme running through all the presentations and identify potential opportunities, suggestions, or recommendations for next steps.
  • What should be the priorities?
  • What are the pressing unanswered questions?
• The Board had the following suggestions:
  • SDRAB should be predicting the trends in supplement use/misuse by the public, not following them
  • Longevity is an increasingly popular topic in the public and longevity medicine should include a consideration of sleep and it currently does not do so broadly enough. This is an opportunity for education about sleep within the clinical community.
  • Chronomedicine and what time of day people should take supplements and medications to maximize therapeutic results is another important area
  • There is an opportunity to explore how GLP-1 agonists affect OSA and sleep in general

The meeting adjourned at 5:00 PM