Funded Projects

NOFO Title: HEAL Initiative: Harm Reduction Policies, Practices, and Modes of Delivery for Persons with Substance Use Disorders (R01 Clinical Trial Optional)
NOFO Number: RFA-DA-22-046
Summary:

Access to harm reduction services are often limited in rural areas. Secondary distribution is a potentially promising strategy for rural areas that involves people sharing harm reduction supplies such as naloxone or fentanyl test strips with other people who use drugs that do not come into contact with harm reduction service providers. This project aims to examine drug use and use of harm reduction services among people in rural communities, as well as highlight factors that make people more or less likely to use secondary distribution approaches.

NOFO Title: HEAL Initiative: HEALthy Brain and Child Development Study (HEALthy BCD) (Collaborative R34 Clinical Trial Not Allowed)
NOFO Number: RFA-DA-19-029
Summary:

The Planning for the HEALthy Early Development Study will contribute to the design and recommended protocol for a future large-scale, multi-site research study to prospectively examine human brain, cognitive, behavioral, social, and emotional development of children beginning prenatally through ages 9–10 and to determine the impact of maternal pre- and postnatal substance use on short- and long-term development of children. The planning study will link investigators across 6 research sites who have complementary experience and expertise in the areas that are essential to designing the study. Planning activities will be accomplished using a coordinated set of 10 working groups. By the end of the planning phase, the 6 consortium sites will have produced and tested a recommended protocol for the future multi-site study and will have established feasibility of carrying out the study protocol at each of the 6 linked sites.

NOFO Title: Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)
NOFO Number: PA-18-591
Summary:

The growing opioid use epidemic in the U.S. has been associated with a significant increase in the prevalence of pregnant opioid-dependent women and neonatal abstinence syndrome, which is associated with adverse health effects for the infant and with costly hospitalizations. Maintenance with sublingual (SL) buprenorphine (BUP) is efficacious for opioid use disorder but has disadvantages that may be heightened in pregnant women, including the potential for poor adherence, treatment dropout, and negative maternal/fetal effects associated with daily BUP peak-trough cycles. Extended release (XR) formulations may address some of these disadvantages. The primary objective of CTN-0080 is to evaluate the impact of treating opioid use disorder in pregnant women (n = 300) with BUP-XR, compared to BUP-SL, on maternal-infant outcomes. Other objectives include testing a conceptual model of the mechanisms by which BUP-XR may improve maternal-infant outcomes, relative to BUP-SL; determining the economic value of BUP-XR, compared with BUP-SL, to treat OUD in pregnant women; and evaluating the impact of BUP-XR, relative to BUP-SL, on neurodevelopment when the infant/child is approximately 12 and 24 months of age. Ultimately, this study will help in increasing access to treatment as well as provide quality care for pregnant/postpartum women.

NOFO Title: PHS 2022-2 Omnibus Solicitation of the NIH and CDC for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44] Clinical Trial Required)
NOFO Number: PA-22-177
Summary:

Reversing an opioid overdose requires a rapid response not available through standard emergency procedures. The Opioid Rapid Response System recruits and trains citizen responders to reverse overdoses with naloxone. It uses widely disseminated smart phone apps linking responders to an overdose through the 911 system. This project will complete the development of this system, test how well it works to reverse an opioid overdose, and prepare to share it widely. 

NOFO Title: Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)
NOFO Number: PA-18-591
Summary:

New medication treatment approaches are needed to help address the severe epidemic of opioid use disorder (OUD) and opioid overdose deaths in the U.S. Currently available medications, such as methadone, buprenorphine, and extended release injection naltrexone (XR-NTX; trade name: Vivitrol), are highly efficacious, but their effectiveness in practice is limited by poor adherence, with many patients stopping treatment prematurely and relapsing. The goal of this proposal is to develop an innovative long-acting subcutaneous implanted formulation of naltrexone, the O’Neil Long-Acting Naltrexone Implant (OLANI), toward FDA approval. Expected to produce naltrexone blood levels sufficient to block the effects of opioids for 6 months after implant, OLANI circumvents the need for adherence to monthly injections with XR-NTX and could represent an important new addition to the medical armamentarium for treatment of OUD.

NOFO Title: Prescription Drug Abuse (R01 Clinical Trial Optional)
NOFO Number: PA-18-058
Summary:

The ongoing opioid crisis has led to renewed concerns about the clinical prescription of addictive opioid analgesics. However, there are currently no suitable alternatives for treating severe or malignant pain. Studies of opioid signaling mechanisms in mice deficient in ?-arrestin have suggested that biased agonists displaying preferential activation of G-protein signaling over ?-arrestin signaling could offer a promising avenue for the development of opioid analgesics with a reduced adverse effects profile. However, there is no concluding evidence showing that such biased signaling can indeed be associated with reduced opioid side effects and, consequently, an improved safety profile. This research will address the need for preclinical data to rigorously evaluate this hypothesis with a program of in vivo studies to compare the effects of “balanced” opioids (morphine, oxycodone, and fentanyl) with that of the “biased” agonists PZM21 and two novel ligands provided by colleagues at the NIDA IRP in nonhuman primates. The results of these studies will provide critical information regarding the dependence liability of “biased” agonists that, in clinical practice, might be given on a repeated, or chronic, basis, potentially adding a powerful new tool for the safer management of severe or malignant pain.

NOFO Title: HEAL Initiative: HEALthy Brain and Child Development Study (Collaborative U01- Clinical Trial Not Allowed)
NOFO Number: RFA-DA-21-020
Summary:

This study aims to determine how exposure to opioids and other substances affects the developing fetal brain and shapes later child cognitive outcomes. Researchers will collect neuroimaging and behavioral data, as well as measures of environmental exposures related to social equity, COVID-19, and socioeconomic factors. The project will reduce traditional barriers to participation by using innovative data collection methods and mobile labs to bring the research to underrepresented and marginalized communities. This approach aims to clarify the impact of substance exposure on child development through an equitable approach to research, with generalizable findings. The study will take place at Rhode Island Hospital, where participants will be drawn from a largely rural population.

NOFO Title: HEAL Initiative: Understanding Polysubstance Use and Improving Service Delivery to Address Polysubstance Use (R01 Clinical Trial Optional)
NOFO Number: DA22-047
Summary:

Compared to people with stable housing, individuals experiencing homelessness are more likely to use both fentanyl and stimulants and experience drug-related harms. This project will examine fentanyl-stimulant polysubstance use patterns and how they evolve over time in response to changes to housing status. It will also assess use of overdose prevention and substance use disorder treatment interventions in homeless individuals who use both fentanyl and stimulants, including how polysubstance use patterns shape their risk of overdose over time. This research will also interact with community stakeholders toward translating the findings into future research, policy, and program recommendations.

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: 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 Number:
Summary:

Emergency department (ED)-initiated buprenorphine/naloxone (BUP) with referral for ongoing BUP is superior to referral alone in engaging patients with untreated opioid use disorder (OUD) in treatment at 30 days and is cost-effective. However, logistical barriers exist in translating research into practice. New BUP formulations such as the extended-release injectable BUP (CAM2038, XR-BUP) hold promise in addressing many of the barriers more effectively than sublingual buprenorphine (SL-BUP) by treating the patients’ symptoms for up to seven days. This study will recruit, train and provide resources to 30 ED sites throughout the U.S. using implementation facilitation strategies to address stigma and provide ED-initiated BUP for patients presenting with OUD who are not receiving medications for OUD. Once implementation is adequately achieved, the sites will conduct a randomized controlled trial (RCT) to compare the effectiveness of SL-BUP versus XR-BUP on ED patients’ engagement in formal addiction treatment seven days after their ED visit. In addition, in an ancillary component of the study, the use of XR-BUP will be assessed in ED patients with Clinical Opioid Withdrawal Scale (COWS) scores of

NOFO Title: Notice of Special Interest to Encourage Eligible NIH HEAL Initiative Awardees to Apply for PA-20-222: Research Supplements to Promote Diversity in Health-Related Research (Admin Supp - Clinical Trial Not Allowed)
NOFO Number: NOT-NS-20-107
Summary:

This research will expand the understanding of the effects of non-invasive vagal nerve stimulation on patients with opioid use disorder by examining the relationship between nerve stimulation and treatment, respiratory physiology, withdrawal symptoms, and relapse. Additionally, these relationships will be added to existing algorithms and equipment being developed by the Inan Research Lab at the Georgia Institute of Technology. Collecting and determining the quality of conventional respiration signals, as well as collecting high-resolution impedance based respiratory measurements, will help to determine the impact of non-invasive vagal nerve stimulation on breathing and lung function in people with opioid use disorder, toward development of a profile of physiological effects of non-invasive vagal nerve stimulation during opioid withdrawal.

NOFO Title: HEAL Initiative: HEAL Data2Action Innovation Projects (R61/R33 Clinical Trial Optional)
NOFO Number: RFA-DA-22-051
Summary:

This project will use a data-to-action framework to guide implementation of opioid use disorder treatment and harm reduction interventions based on rapid data analysis. It will leverage existing data systems such as Emergency Medical Services (EMS) reports, mobile integrated health case management data, and medical examiner data for near real-time data analyses, visualization, and action planning. This research will collect a range of data (opioid treatment, use of acute care services, morbidity, mortality, incarceration, housing support, and cost benefits) from a sub-acute stabilization center for people at high risk for opioid overdose, including those who have recently overdosed and are referred and transported by EMS teams.