Key Dates

Related Announcements

April 24, 2024 - NIH Pathway to Independence Award (Parent K99/R00 – Independent Clinical Trial Not Allowed). See NOFO PA-24-194. 
April 24, 2024 - NIH Pathway to Independence Award (Parent K99/R00 – Independent Clinical Trial Required). See NOFO PA-24-193.
April 24, 2024 - Mentored Clinical Scientist Research Career Development Award (Parent K08 – Independent Clinical Trial Not Allowed). See NOFO PA-24-182.
April 24, 2024 - Mentored Clinical Scientist Research Career Development Award (Parent K08 – Independent Clinical Trial Required). See NOFO PA-24-181.
April 24, 2024 - Mentored Research Scientist Development Award (Parent K01 - Independent Clinical Trial Not Allowed). See NOFO PA-24-176.
April 24, 2024 - Mentored Research Scientist Development Award (Parent K01 - Independent Clinical Trial Required). See NOFO PA-24-175.
April 23, 2024 - Mentored Quantitative Research Development Award (Parent K25 Independent Clinical Trial Not Allowed). See NOFO PA-24-191.
April 09, 2024 - Mentored Patient-Oriented Research Career Development Award (Parent K23 – Independent Clinical Trial Required). See NOFO PA-24-184.
April 18, 2022 - NINDS Exploratory Clinical Trials (UG3/UH3 Clinical Trial Required). See NOFO PAR-22-142.    
May 19, 2021 - NINDS Efficacy Clinical Trials (UG3/UH3 Clinical Trial Required). See NOFO PAR-21-237.
May 10, 2021 - Joint NINDS/NIMH Exploratory Neuroscience Research Grant (R21 Clinical Trial Optional). See NOFO PA-21-219.
May 07, 2020 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed). See NOFO PA-20-195.
May 05, 2020 - Research Project Grant (Parent R01 Clinical Trial Not Allowed). See NOFO PA-20-185.
May 05, 2020 - NIH Research Project Grant (Parent R01 Basic Experimental Studies with Humans Required). See NOFO PA-20-184. 
May 05, 2020 - NIH Research Project Grant (Parent R01 Clinical Trial Required). See NOFO PA-20-183. 

Issued by

National Heart, Lung, and Blood Institute (NHLBI)

National Institute of Neurological Disorders and Stroke (NINDS)

Office of The Director, National Institutes of Health (OD)

All applications to this funding opportunity announcement should fall within the mission of the Institutes/Centers. The following NIH Offices may co-fund applications assigned to those Institutes/Centers.

Office of Research on Women's Health (ORWH)

Purpose

Background and Purpose

Individuals with Postural Orthostatic Tachycardia Syndrome (POTS) suffer from an excessive increase in heart rate (tachycardia) and other symptoms of dysautonomia that worsen upon standing or sitting up, such as light-headedness, shortness of breath, chest pain, and palpitations. These symptoms are disabling for many individuals, with impairments seen in quality of life and multiple domains of physical and social functioning. While disordered autonomic responses (dysautonomia) in POTS are well recognized, the underlying mechanisms driving this response are complex, and there is a need to better characterize the different subtypes of POTS in order to accelerate new diagnostic and therapeutic modalities for this disorder. Many individuals experiencing POTS have reduced intravascular volume which contributes to orthostatic intolerance via mechanisms similar to those seen in deconditioning. Some individuals with POTS also demonstrate evidence of increased cardiovascular adrenergic function suggesting an underlying hyperadrenergic state, additionally small fiber neuropathy and autoimmune factors may also play a role in development of the syndrome.

Epidemiologic studies show that POTS affects women more commonly than men (5:1 predominance of females to males) but the exact prevalence of POTS is unknown. In addition to sex, age, genetic, environmental and other factors influence susceptibility to POTS. Many people with POTS report a preceding medical or life-changing event such as viral infection, concussion, surgery or pregnancy and up to half of individuals report symptoms beginning during adolescence. Recent reports of increased incidence of POTS-like symptoms during the COVID-19 pandemic have further highlighted the possibility of a connection of this syndrome with viral infections, and increases the urgency for robust research to better understand the etiology and mechanisms by which POTS develops.

POTS currently has no curative or standardized therapy and current interventions focus on addressing symptoms rather than underlying pathologic drivers. Some individuals with POTS benefit acutely from dietary salt and volume expansion, however there are limited data on the long-term effects of such therapy. Drug therapies focused on increasing blood pressure, expanding blood volume, and lowering heart rate can also be helpful. Exercise training, with a primary focus on aerobic reconditioning, has also been shown to benefit symptoms.

Research Objectives
POTS is a debilitating condition that affects between 0.2 and 1% of the US population and may be even more prevalent since the COVID-19 pandemic and is often co-morbid in individuals with myalgic encephalomyelitis/chronic fatigue syndrome. The condition impairs individuals' ability to participate in routine activities such as working, attending school, exercising and activities of daily life. POTS primarily affects women of child-bearing age, with most studies reporting 80-90% female predominance. While many individuals with POTS report symptoms beginning in adolescence, up to half of all individuals with POTS develop it in adulthood. The impact of POTS across the lifespan has until now not been well studied, and given the female preponderance of the condition there is an unmet need to study how the condition is impacted by events such as menarche, pregnancy and menopause. 

There is a compelling need to stimulate research focused on improving diagnosis and treatment of POTS. This may include development of biomarkers and diagnostic tools as well as translational studies and mechanistic clinical trials to guide the development of interventions aimed at preventing and curing POTS. This NOSI signals interest in this important area with the goal of stimulating research applications to address these critical needs.

Suggested research examples include, but are not limited to:

• Research to understand causes and mechanisms of POTS, e.g., neuropathology, cardiovascular structure and function, immunology, neurocognitive function
• Diagnostic, prognostic, and monitoring biomarker studies
  • Fluid biomarkers – e.g., blood tests to diagnose POTS or monitor the effect of a therapy
  • Imaging biomarkers – e.g., functional MRI of the brain, PET and SPECT studies of cardiac sympathetic neuronal function
    • Biomarker studies of relevance to NINDS are encouraged to review the NINDS Biomarker Program
  • Wearable and sensor technology that may accelerate diagnosis of POTS
• Studies focused on the longitudinal natural history of POTS, including epidemiologic studies, studies focused on disease presentation and management across the lifespan and throughout different life events such as menarche, pregnancy, and menopause, as well as the association with concurrent conditions and medications
• Studies investigating the influence of sex and/or gender on the development, progression, and outcomes of POTS
• Studies that include representation of patients from populations that experience health disparities
• Genetic and epigenetic studies to understand clustering in families
• Studies investigating the influence of sex and/or gender on the development, progression, and outcomes of POTS Studies that include representation of patients from populations that experience health disparities

NIH strives for rigor and transparency in all research it funds. NINDS explicitly emphasizes the NIH application instructions related to rigor and transparency (https://grants.nih.gov/policy/reproducibility/guidance.htm) and provides additional guidance to the scientific community (https://www.ninds.nih.gov/funding/preparing-your-application/preparingresearch-plan/rigorous-study-design-and-transparent-reporting). For example, the biological rationale for the proposed experiments should be based on rigorous and robust supporting data, which means that data should be collected via methods that minimize the risk of bias and be reported in a transparent manner. If previously published or preliminary studies do not meet these standards, applicants should address how the current study design addresses the deficiencies in rigor and transparency. Proposed experiments should likewise be designed in a manner that minimizes the risk of bias and ensures validity of experimental results.  The proposed clinical trial must be based on robust and rigorous supporting data (e.g., from non-clinical in vivo and/or in vitro studies or preliminary clinical studies) that demonstrate that there is an adequate scientific foundation to justify the proposed trial. The proposed trial design must also use rigorous and transparent approaches.

Application and Submission Information

Applicants must select the IC and associated NOFO to use for submission of an application in response to the NOSI. The selection must align with the IC requirements listed in order to be considered responsive to that NOFO. Non-responsive applications will be withdrawn from consideration for this initiative.

In addition, applicants using NIH Parent announcements (listed below) will be assigned to those ICs on this NOSI that have indicated those NOFOs are acceptable and based on usual application-IC assignment practices.

This notice applies to due dates on or after October 05, 2024, and subsequent receipt dates through January 7, 2028. This NOSI expires on January 8, 2028; thus no applications will be accepted on or after January 8, 2028.

Submit applications for this initiative using one of the following Notices of Funding Opportunity (NOFOs) or any reissues of these announcements through the expiration date of this Notice. 

All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:

• For funding consideration, applicants must include NOT-HL-24-018 in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative. NINDS and NHLBI will accept applications that are within the mission of the respective Institute.

Applications nonresponsive to terms of this NOSI will not be considered for the NOSI initiative.

Inquiries

Please direct all inquiries to the contacts in Section VII of the listed notice of funding opportunity with the following additions/substitutions:

Scientific/Research Contact(s) 
Marc Charette, PhD
National Heart, Lung and Blood Institute (NHLBI)
Telephone: 301-435-0560
Email: [email protected]

Vicky Whittemore, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 240-274-6696
Email: [email protected]


Financial/Grants Management Contact(s) 
Lynn Rundhaugen
National Heart, Lung and Blood Institute (NHLBI)
Telephone: 301-480-4546
Email: [email protected]

Chief Grants Management Officer
National Institute of Neurological Disorders and Stroke (NINDS)
Email: [email protected]