Funded Projects

NOFO Title: HEAL Initiative: Translating Research to Practice to End the Overdose Crisis (R33 Clinical Trial Optional)
NOFO Number: RFA-DA-23-054
Summary:

Computerized clinical decision support tools offer a promising strategy to standardize and scale evidence-based practices to keep pace with the dynamic nature of the opioid crisis and overcome barriers to substance use disorder treatment. To change practice, such tools must be useful, usable, able to be integrated into routine care delivery, and supported by a multicomponent implementation strategy. This project will refine and evaluate the uptake, usability, and equity of a nationally disseminated multicomponent clinical decision support intervention to increase initiation of medication treatment for opioid use disorder in the emergency department.

NOFO Title: Career Development Awards in Implementation Science for Substance Use Prevention and Treatment (K01 - Clinical Trial Required) 
NOFO Number: PAS-22-206
Summary:

Many people with opioid use disorder (OUD) also have a serious mental illness and other chronic conditions, which can be difficult for individuals and primary care providers to manage. A chronic disease self-management program is an established health care model in which peers help to educate patients about their condition(s) and build problem-solving skills to manage their health. Such programs have been effective in other populations and settings, but they have not been adapted for primary care patients who have OUD and SMI. This project will adapt and test a chronic disease self-management program for this population to understand its feasibility, acceptability, impact, and how best to put such programs into place widely in primary care settings.

NOFO Title: HEAL Initiative: Notice of Special Interest (NOSI) regarding the Availability of Administrative Supplements to Support Strategies to Increase Participant Diversity, Inclusion and Engagement in Clinical Studies
NOFO Number: NOT-NS-21-025
Summary:

Effective medications for opioid use disorder (MOUD) are approved by the Food and Drug Administration for the treatment of people with opioid use disorder; however, only a small fraction of patients who would benefit from these medications actually use them. Several reasons contribute to low MOUD use, including lack of insurance; lack of knowledge about the medications, both among patients and providers; stigma associated with MOUD; and social norms. Innovative methods are needed to help increase MOUD use. One such option is peer-led interventions that might increase patients’ interest in MOUD. One existing peer-led intervention is the Harnessing Online Peer Education (HOPE) online community intervention that has been designed to reduce stigma and increase health behavior change among stigmatized populations, such as people living with HIV. This project will investigate whether and how HOPE can be adapted for people with opioid use disorder. It will assess whether HOPE can effectively increase MOUD requests, MOUD uptake, and sustained adherence to MOUD as well as reduce overdose rates.  

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:

Acute and chronic low back pain are among the most common sources of short- and long-term disability. Fear of pain and disability, or “catastrophizing,” increases opioid use, but is reduced when patients have effective options and feel control over pain. The goal of this project is to develop an opioid-sparing therapeutic consumer device for low back pain, with multiple patient-controlled effective neuromodulatory pain relief options, including vibration, pressure, cold, and heat. After proving that providing a multimodal device is effective for pain, the project will determine whether the availability of an effective home therapy device reduces opioid use for patients with acute and chronic low back pain.

NOFO Title: HEAL Initiative: Advancing Health Equity in Pain Management (R61/R33 Clinical Trial Required)
NOFO Number: NS22-002
Summary:

This research project will include focus group interviews with clinicians, patients, medical interpreters, and healthcare administrators to identify barriers and facilitators to administering the GetActive+ intervention in a group visit at a clinic for older adults with chronic pain, to inform development of a therapy manual. The project will then test the GetActive+ intervention for changes in physical function immediately post-intervention and after 6 months, as well as for changes in pain, sleep, depression, and anxiety at both time points. This research will also assess feasibility, acceptability, fidelity, and adoption of the intervention with patients, providers, and healthcare staff. 

NOFO Title: Development of Vaccines for the Treatment of Opioid Use Disorder
NOFO Number: BAA-DAIT-75N93019R00009
Summary:

High rates of relapse and overdose deaths pose significant challenges to the treatment of Opioid Use Disorder (OUD). Anti-opioid immunotherapies (i.e., vaccines and monoclonal antibodies) have great potential to reduce long-term opioid use and overdose, with minimal risk of side effects, when used in conjunction with pharmacological treatments and/or behavioral therapies. The ability of an anti-opioid vaccine to induce antibodies that render an opioid less effective, or less rewarding, and protect from accidental overdose could provide an important therapeutic option for patients undergoing treatment for OUD. The goal of this collaborative study is to design, develop, and evaluate vaccines for use in the treatment of opioid use disorder

NOFO Title: HEAL Initiative: Notice of Special Interest (NOSI) regarding the Availability of Administrative Supplements to Support Strategies to Increase Participant Diversity, Inclusion and Engagement in Clinical Studies
NOFO Number: NOT-NS-21-025
Summary:

The ACT NOW Outcomes of Babies with Opioid Exposure (OBOE) Study – also called the ACT NOW Longitudinal Study – is a longitudinal cohort study to prospectively examine longitudinal outcomes from birth to 2 years of age among infants who were exposed to opioids in utero as compared to matched controls. The objectives of this study are to i) determine the impact of pre-birth opioid exposure on brain structure and connectivity over the first 2 years of life, ii) define medical, developmental, and behavioral outcomes over the first 2 years of life in infants exposed to opioids, and iii) Explore whether and how the home environment, maternal mental health, and parenting affect brain connectivity and neurodevelopment trajectories over the first 2 years of life. This research will use an innovative approach to engage a more diverse study population and thereby improve the generalizability of the research findings.

NOFO Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
NOFO Number: RFA-DA-19-002
Summary:

Kinoxis has developed a novel small-molecule lead, KNX100, that reduces the severity of opioid withdrawal symptoms in preclinical animal models of opioid use disorder (OUD). KNX100 was discovered from a phenotypic screen of compounds derived from a fragment-based drug discovery program targeting the brain oxytocin system. KNX100 has a favorable pharmacokinetic and safety profile and has undergone testing for efficacy signals in two rodents and two non-human primate species. The proposed activity is to progress the development of KNX100 to treat opioid withdrawal in OUD. The overall objective of the project is to establish the safety and tolerability of KNX100 to enable human efficacy testing to commence in patients requiring treatment for opioid withdrawal. The long-term objective for this development program is to generate human efficacy data to support KNX100 as a potential treatment for opioid withdrawal symptoms and ultimately enable a New Drug Application to the FDA.

NOFO Title: Research Networks for the Study of Recovery Support Services for Persons Treated with Medications for Opioid Use Disorder (R24 Clinical Trial Optional)
NOFO Number: RFA-DA-20-014
Summary:

Individuals with opioid use disorder tend to be more in need of additional services; feel more isolated and marginalized; have less available resources such as education, training, employment, and housing opportunities (collectively known as “recovery capital”); and report lower quality of life than those with other substance use disorders. Recovery Community Centers (RCCs) are designed specifically to help grow recovery capital and enhance remission and quality of life. Preliminary evidence suggests RCCs are particularly valuable for people with opioid use disorder, but little is known about their clinical and public health benefits and cost-effectiveness. This project will organize activities on a national level to enhance research on RCCs. It builds on existing professional and academic resources, including an established recovery dissemination platform (i.e., the Recovery Research Institute).

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

Persistent pain states arising from inflammatory conditions, such as in arthritis, diabetes, HIV, and chemotherapy, exhibit a common feature in the release of damage-associated molecular pattern molecules, which can activate toll-like receptor-4 (TLR4). Previous studies suggest that TLR4 is critical in mediating the transition from acute to persistent pain. TLR4 as well as other inflammatory receptors localize to lipid raft microdomains on the plasma membrane. We have found that the secreted apoA-I binding protein (AIBP) accelerates cholesterol removal, disrupts lipid rafts, prevents TLR4 dimerization, and inhibits microglia inflammatory responses. We propose that AIBP targets cholesterol removal to lipid rafts harboring activated TLR4. The aims of this proposal are to: 1) determine whether AIBP targets lipid rafts harboring activated TLR4; 2) test whether AIBP reduces glial activation and neuroinflammation in mouse models of neuropathic pain; and 3) identify the origin and function of endogenous AIBP in the spinal cord.

NOFO Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
NOFO Number: RFA-DA-19-002
Summary:

The excruciating multiday experience of opioid withdrawal syndrome (OWS), is exacerbated by the opioid antagonist drugs naloxone and naltrexone. This industry-academia collaboration will explore the potential of the glutamate AMPA receptor antagonist Tezampanel (TZP). Animal studies have shown reduced hyperactivity in brain circuits involved in OWS, without relying on direct stimulation or antagonism of the opioid system ,and has already been delivered to over 500 human subjects and found to be safe for a potential migraine indication. This proposal will build up the evidence needed to apply for and conduct open label and blinded placebo-controlled human trials of TZP safety and efficacy for OWS. If successful, this project will allow planning for a pivotal registration trial for TZP for OWS, and as a transitional treatment to long-term recovery on naltrexone and help us stem the tide of the opioid crisis.

NOFO Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
NOFO Number: PAR-20-092
Summary:

There are currently no effective non-opioid-based pharmacotherapies for treatment of opioid use disorder (OUD). Glial cell line-derived neurotrophic factor (GDNF) is a beneficial protein normally present in low levels in the adult brain, and there is strong evidence that it has clinical potential as a therapy for OUD and relapse reduction. Researchers have developed a non-invasive approach that bypasses the blood-brain barrier to increase levels of GDNF using intranasal administration of gene nanoparticles that make GDNF protein within the brain. This project will test whether this intranasal GDNF gene therapy can suppress drug craving and reduce the tendency to start using a drug again after a period of abstinence in experimental models, thus providing a long-term therapeutic strategy for reducing opioid craving and preventing relapse.

NOFO Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
NOFO Number: RFA-DA-19-002
Summary:

Buprenorphine (BUP) is an FDA-approved medication-assisted therapy (MAT) that improves outcomes and saves lives in patients with opioid use disorder (OUD). It is available in multiple dosage forms and routes of administration, including daily sublingual (SL) and buccal tablets and films, a monthly subcutaneous (SC) injectable, and a 6-month SC implant; however, these forms leave many patients untreated or undertreated. This product, in a partnership with Lyndra Therapeutics, aims to develop a once-weekly oral BUP dosage form for maintenance therapy for OUD, using a new oral dosage formulation developed by Lyndra. A long-acting oral BUP may address important limitations of current MATs by providing improved PK with less euphoria than SL, a patient- and provider-preferred route of administration, and an optimal dosing interval for improved patient adherence with the potential for cost-effective direct observed therapy.