Request for Applications

Issued: November 12, 2021
Request for Applications

SmartTots is accepting research grant applications aimed at continuing the ongoing work to advance the knowledge and understanding of the effects of anesthetics on the developing brain and address current unknowns. Both clinical and preclinical projects are welcome. New projects building on the work of an earlier study are encouraged. Pilot projects will be considered. Apply now!

Request for Applications

Deadline: February 28, 2022

SmartTots, a Public-Private Partnership between the International Anesthesia Research Society (IARS) and the U.S. Food and Drug Administration (FDA), is a multi‐year collaborative effort to increase the safety of anesthetic drugs for the millions of infants and children who undergo anesthesia each year.

Background

Laboratory animals exposed to most anesthetic and sedative drugs early in life show changes to the brain and nervous system that can interfere with memory, learning, and behavior.  Accumulating clinical data in young children suggest alterations in behavior but not cognition in single and multiple exposures.  All of the human studies to date have had significant limitations that make it impossible to conclusively determine whether anesthesia, surgery, hospitalization, or pre-existing conditions caused the observed effects. Additional research is needed to assess the effects of anesthetics and sedatives on the developing human brain.

Request for Applications

SmartTots is accepting applications aimed at continuing the ongoing work to advance the knowledge and understanding of the effects of anesthetics on the developing brain and address current unknowns. Both clinical and preclinical projects are welcome. New projects continuing the work of an earlier study are encouraged. Pilot projects will be considered.

Specific questions of interest include:

  • What additional nonclinical data are necessary to more clearly define the potential window of vulnerability in humans given the diversity of possible endpoints and models available (e.g., significance of alterations in neuronal architecture vs apoptosis, additional functional behavioral endpoints such as social interaction data that may be more predictive of human outcome measures).
  • What are the histological and functional endpoints and outcome measures to determine drug dose-duration relationships in rats and non-human primates?
  • What is the impact of anesthetic and sedative agents on brain development in animal models of long-term sedation in the ICU, or repeated subanesthetic exposures for procedural sedation or pain control?
  • What additional nonclinical data can more fully inform what durations of exposure to these agents may not result in adverse effects beyond neuroapoptosis?
  • What is the threshold dose-duration for a single exposure and for multiple exposures needed to cause: (a) abnormal cell death; (b) changes in synaptic connectivity/spine formation; (c) functional deficits?
  • Are these effects variable by brain region?
  • What is the exact period of sensitivity to these effects?
  • How does this period of sensitivity relate to human development?
  • Are there differences among anesthetic agents?
  • Are there differences when agents are combined?
  • Are there differences between males and females?
  • What are the effects on brain development of opioids and other drug combination regimens commonly used in pediatric clinical practice?
  • Are there “safe” anesthetic agents?
  • Are there agents that prevent or mitigate the adverse effects associated with general anesthesia? At what dose and under what conditions?
  • Can the adverse effects of anesthesia be mitigated by behavioral means, such as environmental enrichment? Which human populations are at greatest risk?
  • Are the effects greater in more vulnerable subgroups (e.g. in utero, premature infants and those with serious comorbidities)?
  • Can the effects of anesthesia be separated from the effects of surgery or the underlying condition?
  • Are there biomarkers of exposure to anesthetic agents, e.g. imaging studies, that can serve as intermediate outcomes that could be associated with longer term neurobehavioral outcomes?

Applicant Eligibility Criteria

  • Applicants must hold an MD or PhD degree from an accredited institution.
  • The official online application at ProposalCentral must be used.
  • All information and attachments requested in the application must be supplied. Failure to do so will disqualify the application
  • A maximum of $250,000 will be awarded. SmartTots may select a single application or multiple applications to be funded.
  • Matching support from the applicant’s institution is encouraged.
  • Applications will be reviewed by a multidisciplinary team of experts assigned by the SmartTots Steering Committee to maintain the scientific merit of all SmartTots-funded research projects.
  • Grants will be awarded at the sole discretion of the SmartTots Steering Committee based on their relevance and probability of success.

Inquiries

Inquiries about the program guidelines, eligibility and application materials can be directed to IARS.  Please contact the IARS Research Programs Director at (415) 296-6905, or by email at [email protected]

Request for Applications

SmartTots is accepting research grant applications aimed at continuing the ongoing work to advance the knowledge and understanding of the effects of anesthetics on the developing brain and address current unknowns. Both clinical and preclinical projects are welcome. New projects building on the work of an earlier study are encouraged. Pilot projects will be considered.

Full Application Guidelines

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