Funded Projects

NOFO Title: Development of a Device to Objectively Measure Pain (R43/R44)
NOFO Number: RFA-DA-18-012
Summary:

While patient self-report of pain is the gold standard of pain measurement, this may not be feasible in critically ill patients who are sedated and intubated, unconscious, or unable to verbally communicate. Pupillary dilation (PD) is a reliable indicator of acute pain, and measurement of pupil size changes may be useful in determining the intensity of pain experienced as well as the efficacy of an analgesia. Research also demonstrates that pupillary unrest under ambient light (PUAL) is an objective marker of sensitivity to opioids, and facial expression analysis can help detect pain. Benten Technologies, Inc. aims to develop and validate IMPACT, a device that uses pupillometry with a proprietary algorithm to measure both PD and PUAL and conduct facial expression analysis using computer vision. The project team will then demonstrate the feasibility of IMPACT in helping clinicians objectively determine pain and assess opioid efficacy and compare results obtained to pain scores reported by patients.

NOFO Title: PHS 2018-02 Omnibus Solicitation of the NIH, CDC, and FDA for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44] Clinical Trial Not Allowed)
NOFO Number: PA-18-574
Summary:

This project seeks to develop a first-in-class (FIC), peripherally restricted and long-acting drug with potential to reduce or replace opioid for moderate to severe pain, and that will be non-addictive, safe, and convenient to use. The program is based on strong scientific evidence showing that activation of a receptor called MAS1 produces opioid-independent and peripheral pain relieving activity in a wide range of animal models of chronic pain, including inflammatory, neuropathic, and bone cancer pain. This project focuses on the development of potent, stable, and specific molecules that stimulate MAS1. Researchers will then attach peptides that stimulate MAS to antibody carriers that make them last longer and selectively affect only the peripheral nervous system, which could allow for once a week or twice a month dosing while maintaining the drug’s efficacy and reducing potential side effects, and test the resulting molecule in animal models.

NOFO Title: PHS 2018-02 Omnibus Solicitation of the NIH, CDC, and FDA for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44] Clinical Trial Not Allowed)
NOFO Number: PA-18-574
Summary:

Maternal use and addiction to opioids or other drugs has resulted in an unprecedented rise in drug withdrawal complications in newborns known as neonatal abstinence syndrome (NAS). While there is no accepted standard for treating NAS, non-pharmacological bundles are recommended as an initial course of treatment. Unfortunately, non-pharmacological care (swaddling, rocking, frequent feedings, and skin contact) require significant use of human resources. This project studies the technical feasibility of a stochastic vibrotactile stimulation (SVS) technology incorporated into the hospital bassinet pad, which provides gentle vibrating sensory stimulation to soothe infants with NAS. Building on preliminary evidence that this type of stimulation calms NAS infants without altering their sleep, this study aims to develop a commercially viable bassinet pad that could be used in a hospital setting.

NOFO Title: HEAL Initiative: America’s Startups and Small Businesses Build Technologies to Stop the Opioid Crisis (R43/R44 - Clinical Trial Optional)
NOFO Number: RFA-DA-19-019
Summary:

The orbitofrontal cortex (OFC) plays an important role in regulation of addiction, and OFC impairment from cocaine and opioids use leads to repetitive drug use. Brief optogenetic activation of the OFC reduces self-administration of drugs in neurobiology studies. However, the OFC is less accessible for noninvasive stimulation using direct transcutaneous current stimulation or transcranial magnetic stimulation. The small business EvON Medics LLC and Howard University have created a home-based olfactory pulsing prototype, called computerized chemosensory-based orbitofrontal cortex training (CBOT), using a high-fidelity chemosensory and computerized olfactory training approach to enable home-based neuromodulation of the OFC for treatment of opioid use disorder (OUD). A pilot feasibility study in OUD samples suggests that CBOT can minimize withdrawal symptoms, reduce drug cravings, enhance positive affect, and reduce rate of positive urine drug tests. The project seeks to establish CBOT stimulation parameters needed to maximally improve outcome inference and emotion regulation in OUD.

NOFO Title: HEAL Initiative: America’s Startups and Small Businesses Build Technologies to Stop the Opioid Crisis (R43/R44 - Clinical Trial Optional)
NOFO Number: RFA-DA-19-019
Summary:

Neonatal Opioid Withdrawal Syndrome (NOWS) affects a growing number of neonates each year due to the ongoing opioid epidemic ravaging the United States. Complex neurobehavioral observation of newborns is the primary modality used. It is subjective and time-consuming by nature, requires significant expertise, and can lead to delays in treatment. The goal of this project is to develop an innovative, low-cost, non-invasive, and easy-to-use brain monitor to objectively assess the severity of withdrawal symptoms in newborns exposed to opioids and provide evidence-based decision support to care providers to improve both short- and long-term developmental outcomes. This device, referred to as NeoGUARD, is based on the continuous, automated, and real-time monitoring of brain function to detect EEG abnormalities shown to be related to NOWS and determine severity to guide pharmacological intervention. This study will focus on the initial prototyping and refinement of the hardware and software, as well as initial evaluations of its use.

NOFO Title: PHS 2018-02 Omnibus Solicitation of the NIH, CDC, and FDA for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44] Clinical Trial Not Allowed)
NOFO Number: PA-18-574
Summary:

This project, a partnership with Principled Strategies, will develop innovative, patient-level models for opioid risk identification and integrate them into the SafeUseNow managed care system—an actionable solution for combating prescription drug abuse that currently operates at the prescriber level only. Incorporating patient-level risk identifier models will strengthen an already powerful and demonstrably effective program and constitutes a critical step in generating a first-in-class, multifactor risk assessment strategy that is truly holistic. Using a variety of data sources, advanced analytics, and multiple empirically validated risk identification models, the groundbreaking advancement in SafeUseNow technology will enable health care stakeholders to identify combinations of prescribers, patients, and pharmacies whose behaviors may contribute to prescription drug abuse. This project will work to obtain new datasets for analysis, assess them, and use them to build national patient-level risk models for relevant outcomes, which will enable the development and evaluation of a next-generation prototype for a patient-level version of SafeUseNow.

NOFO Title: HEAL Initiative: America’s Startups and Small Businesses Build Technologies to Stop the Opioid Crisis (R43/R44 - Clinical Trial Optional)
NOFO Number: RFA-DA-19-019

NOFO Title: HEAL Initiative: America’s Startups and Small Businesses Build Technologies to Stop the Opioid Crisis (R43/R44 - Clinical Trial Optional)
NOFO Number: RFA-DA-19-019
Summary:

This project aims to demonstrate the safety and effectiveness of a novel treatment for opiate addiction using a technique called photobiomodulation, application of light to the forehead. The treatment consists of using a 4-minute application of transcranial photobiomodulation, near-infrared mode, through a supra-luminous LED, to one side of the forehead over the brain hemisphere that has been determined to have a more positive emotional valence. The study will examine differences in opioid cravings, anxiety, depression, and opioid use between participants receiving the treatment and those receiving a sham treatment. We will evaluate patients weekly for safety and efficacy for 3 weeks post-treatment. In Aim II, a highly-regarded product engineer will work with the company to design a marketable product that may have patentable elements.

NOFO Title: HEAL Initiative: America’s Startups and Small Businesses Build Technologies to Stop the Opioid Crisis (R43/R44 - Clinical Trial Optional)
NOFO Number: RFA-DA-19-019
Summary:

Pain is one of the most common and debilitating symptoms of a wide range of injuries and diseases. Safe and effective alternatives for treating pain that reduce dependence on opioids are, therefore, a primary goal of the NIH. This project proposes a non-invasive, non-pharmacological alternative to treat pain by combining an innovative electroencephalography (EEG)-based Neurofeedback (NF) solution in an immersive virtual reality (VR) environment. NF and VR have been shown to independently produce ameliorative effects on pain, and it is hypothesized that an NF training in VR would have synergistic effects, as VR would distract from pain perception to improve patient compliance in more engaging NF protocols that improve their ability to control pain perception. In the scope of this project, we will initially focus our work on chronic low back pain (cLBP), as this is a growing segment of chronic pain sufferers with a 39 percent worldwide lifetime prevalence, and whose sufferers have historically been heavy users of opiates; later stages of this project will expand this application to address other forms of pain.

NOFO Title: HEAL Initiative: America’s Startups and Small Businesses Build Technologies to Stop the Opioid Crisis (R43/R44 - Clinical Trial Optional)
NOFO Number: RFA-DA-19-019
Summary:

With nearly 116 million people suffering from chronic pain in the United States, there is a need for new analgesics without the risks posed by opioids. Antagonists acting at TRPV1 receptor have long been recognized as one of the most promising novel classes of non-opioid analgesics. Initial tests in humans have confirmed that this class of drugs produces analgesia and is safe and well-tolerated, but side effects include hyperthermia and partial loss of heat sensitivity, leading to most research being halted. This project will conduct a set of preclinical proof-of-concept studies in rats to support the claims that, at doses that have minimal, clinically acceptable, or negligible impact on cardiovascular function, a2 adrenoceptor agonists can diminish thermoregulatory effects of TRPV1 receptor antagonists.

NOFO Title: HEAL Initiative: America?s Startups and Small Businesses Build Technologies to Stop the Opioid Crisis (R43/R44 - Clinical Trial Optional)
NOFO Number: RFA-DA-19-019
Summary:

One novel approach to address the opioid crisis is predicting the likelihood of retention in treatment for opioid use disorder (OUD) by assessing someone?s risk of early departure from treatment. Current methods rely on providers intuition to identify when an individual is at risk of leaving treatment early in order to intervene. This intervention, when it happens, often comes too late. Mobile health (mHealth) and Machine Learning (ML) predictive analytics offer a new opportunity to personalize OUD treatment, improve retention in OUD care, and mitigate the risk of relapse and overdose episodes. Project Motivate will combine physiological and behavioral data from disparate sources in order to predict when an individual is at risk of early departure from OUD treatment. If successful, results of the study will save lives, and lower medical costs, municipal emergency response costs, recidivism, workplace accidents, lost workplace productivity and costs to families.

NOFO Title: PHS 2017-02 Omnibus Solicitation of the NIH, CDC, and FDA for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44])
NOFO Number: PA-17-302
Summary:

From 2009 to 2013, the utilization of the Schedule II opioids codeine, OxyContin, and fentanyl declined significantly, down about 14 percent for all three drugs. In sharp contrast, the use of tramadol, a Schedule IV controlled substance, increased by 32.5 percent. Schedule IV substances have lower potential for abuse and harm than Schedule II substances, and the fortuitous trend to tramadol has reduced the use of the relatively unsafe Schedule II opioids dramatically. However, tramadol is less effective in some individuals with a particular gene variant that makes them unable to metabolize it well. A new analgesic, omnitram, uses similar mechanisms to tramadol but is not as dependent on this gene. This SBIR Fast-Track project will conduct a Phase 1 clinical trial of Omnitram in normal human subjects. Success in this in-patient Phase 1 clinical trial will provide direct support for Omnitram’s continued clinical development toward FDA approval.

NOFO Title: Loyalty and Reward-Based Technologies to Increase Adherence to Substance Use Disorder Pharmacotherapies (R43/R44 - Clinical Trial Optional)
NOFO Number: RFA-DA-19-014
Summary:

Opioid use disorder (OUD) is a key driver of the current opioid epidemic in the United States, but nearly 80% of individuals with OUD do not receive treatment. Buprenorphine medication-assisted treatment (MAT) is an effective form of care for OUD. This project will develop a state-of-the-art, digital therapeutic tool that effectively promotes buprenorphine adherence by providing contingency management rewards and educational content and enables home induction using a new self-monitoring support tool. This tool, named reSET-O+, will be integrated with Pear Therapeutics’ reSET-O, an FDA market-authorized mobile application delivering validated behavioral therapy and intended for use in conjunction with buprenorphine and standard outpatient treatment for OUD.