Funded Projects

NOFO Title: HEAL Initiative: Pharmacotherapies to Reverse Opioid Overdose Induced Respiratory Depression without Central Opioid Withdrawal (Target Validation and Candidate Therapeutic Development (R61/R33 - Clinical Trial Not Allowed)
NOFO Number: RFA-HL-20-031

NOFO Title: Discovery and Validation of Novel Targets for Safe and Effective Pain Treatment (R01 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-18-043
Summary:

Chemotherapy-induced painful peripheral neuropathy (CIPN) is the most common toxicity associated with widely used chemotherapeutics. CIPN accounts for significant dose reductions and/or discontinuation of these life-saving treatments. Unfortunately CIPN can also persist in cancer-survivors, adversely affecting their quality of life. CIPN is not well-managed with existing pain therapeutics. Recent preliminary findings suggest that the transcription factor hypoxia-inducible factor alpha (HIF1A) is the target for the chemotherapeutic bortezomib, a proteasome inhibitor. This project will test the hypothesis that bortezomib chemotherapy-induced expression of HIF1A, PDHK1 and LDHA constitute an altered metabolic state known as aerobic glycolysis (AG) that leads to the initiation and maintenance of peripheral neuropathy and pain using a novel tumor-bearing animal model of CIPN. This project aims to validate HIF1A as a therapeutic target for the prevention of CIPN, as well as validate PDHK1 and LDHA as non-opioid therapeutic targets for chronic or established CIPN in animal models.

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

Use of both opioids and stimulants is increasing, but little is known about how polysubstance use evolves over time and how it influences overdose risk. This project will use data from two groups at high risk for overdose: i) participants in the AIDS Linked to the IntraVenous Experience (ALIVE) study who inject drugs and ii)  participants in the new Stimulant Opioid Non-Injection Cohort (SONIC) study. This research will identify drug use patterns and their association with treatment and overdose over time – toward informing overdose prevention efforts and interventions to improve the U.S. opioid crisis.

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

Although methadone is an effective treatment for opioid use disorder, many individuals drop out of treatment, putting them at risk of relapse and overdose. One of the factors associated with poor retention in methadone treatment is concurrent cocaine use. There is currently no effective medical treatment for cocaine use disorder. However, contingency management, in which individuals receive tangible rewards for desired behaviors such as abstinence, has been shown to be effective for cocaine use. This project will test the value of a digital therapy app, DynamiCare Health Contingency Management, in methadone treatment programs to promote treatment for polysubstance use.

NOFO Title: Midcareer Investigator Award in Patient-Oriented Research (Parent K24 Independent Clinical Trial Required)
NOFO Number: PA-20-193
Summary:

The HEAL-funded Sequenced-strategy for Improving Outcomes in People with Knee Osteoarthritis Pain (SKOAP) clinical trial evaluates behavioral, pharmacologic, and procedural interventions for patients with knee osteoarthritis pain. It is designed to mimic clinical care for these patients by first testing the effectiveness of conservative and nonsurgical interventions before considering surgical interventions. It is a large-scale clinical trial with a novel design that evaluates multidisciplinary treatments. Therefore, it offers a unique training opportunity for junior investigators from various disciplines who are interested in pain research and management. This mentoring award will allow a selected investigator to train junior investigators by providing protected, mentorship-focused time.

NOFO Title: Discovery and Validation of Novel Targets for Safe and Effective Pain Treatment (R01 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-18-043
Summary:

Pain associated with surgery is experienced by millions of patients every year. Although post-surgical pain usually resolves as the surgical site heals, up to half of the patients develop chronic pain after surgery. Opioids remain the mainstay treatment for post-surgical pain which are fraught with serious side-effects and abuse liabilities. The endogenous mechanism that leads to the resolution of post-surgical pain remain unclear, specifically the effects of surgery on the metabolism of sensory neurons and how those changes influence the resolution of post-surgical pain are not known. Preliminary findings suggest that surgical trauma suppresses pyruvate oxidation while increased glutamine catabolism was associated with the resolution of post-surgical pain. This project will test the hypothesis that tissue incision and surgery disrupt the expression of the glutamine transporter ASCT2, which then prevents the resolution of post-incisional pain and aims to validate ASCT2 as a therapeutic target. This project will also employ pharmacological, genetic and animal pain model studies test a novel RNA expression-based strategy to enhance ASCT2 expression in DRG sensory neurons and alleviate postoperative pain in animal model systems. Successful completion of this project would validate ASCT2 as a novel endogenous non-opioid and non-addictive mechanism-based target for the resolution of postoperative pain.

NOFO Title: CTSA Network - Trial Innovation Centers (TICs) (U24)
NOFO Number: RFA-TR-15-002

NOFO Title: HEAL Initiative: HEAL Data2Action Data Infrastructure Support Center
NOFO Number: RFA-DA-22-046
Summary:

This project will evaluate a previously developed harm reduction intervention that addresses the needs of women who use drugs in an urban environment. The approach uses a mobile van to offer naloxone, fentanyl test strips, and other harm reduction supplies – along with necessities such as food and clothing, brief trauma-informed counseling, and referrals to drug treatment, medical care, and social services. This research aims to test the impact of an intervention that may increase access to harm reduction services for women, as well as assess how to put it into place.

NOFO Title: HEAL Initiative: Behavioral Research to Improve MAT: Behavioral and Social Interventions to Improve Adherence to Medication Assisted Treatment for Opioid Use Disorders (R61/R33 Clinical Trial Optional)
NOFO Number: RFA-AT-19-006
Summary:

Young people are disproportionately affected by the opioid crisis due to lack of access to medications for opioid use disorder (OUD) and poor adherence to these treatments. The Youth Opioid Recovery Support (YORS) model is an innovative wraparound approach that attempts to address barriers to treatment engagement in the young adult population, especially difficulties with medication adherence. The YORS model components include home delivery of extended-release naltrexone for OUD, engagement of families in collaborative treatment planning and monitoring focusing on medication adherence, assertive outreach from the treatment team by text messaging and social media to promote engagement and adherence, and contingency management to provide incentives for medication adherence. If the refining and testing demonstrates the efficacy of the YORS intervention, future work could include an economic analysis, a larger multisite study, longer intervention duration, study of extended-release buprenorphine, and study of step-down to less intensive interventions.

NOFO Title: Discovery and Validation of Novel Targets for Safe and Effective Pain Treatment (R01 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-18-043
Summary:

As many as 64% of patients with Temporomandibular Joint Disorders (TMJDs) report symptoms consistent with Irritable Bowel Syndrome (IBS). However the underlying connection between these comorbid conditions is unclear and treatment options are poor. As such, pain management for these Chronic Overlapping Pain Conditions (COPCs) is a challenge for physicians and patients. This project will determine whether the convergence of pain from different peripheral tissues and perceived stress occurs in the brain and elicits a change in central neural processing of painful stimuli. This project will identify and validate specific lipids, enzymes and metabolic pathways that change expression in the brain during the transition from acute to chronic overlapping pain that can be therapeutically targeted to treat COPCs. Multi-disciplinary approaches will be used to combine brain imaging, visualization of spatial distribution of molecules, genetics, pharmacological and behavioral research techniques.

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

The parent U19, “Southwest Hub for American Indian Youth Suicide Prevention,” builds capacity among local tribal governments, investigators, interventionists, and service providers across three Southwestern states to: 1) identify at-risk youth and gather robust local data through surveillance; 2) provide regular monitoring and brief interventions to close gaps in continuity of care; and 3) convene regularly for shared learning, policy development, and dissemination of best practices. The parent U19 includes an innovative SMART trial study design. The purpose of this supplement is to gather data on opioid use. Our supplement aims are to: 1) expand suicide surveillance in the Southwest Hub to include opioid use as a potential precipitant, facilitator, and risk factor for subsequent suicidal behavior; 2) explore community beliefs about correlates of risk, protective factors, and behavior functions of opioid abuse in Native American youth; and 3) examine opioid use among SMART trial participants.

NOFO Title: HEAL Initiative: Translational Devices to Treat Pain (UG3/UH3 Clinical Trial Optional)
NOFO Number: RFA-NS-19-016
Summary:

Currently, there are no adequate therapies for abdominal pain in patients with Irritable Bowel Syndrome (IBS), a gastrointestinal disorder affecting 14-20% of the US population. More than 40% of IBS patients regularly use opioid narcotics. An alternative treatment for IBS that has been shown to be an effective pain management strategy is electroacupuncture. However its drawbacks include infrequent administration, unclear mechanistic understanding, and lack of methodology optimization. This study will use a noninvasive method of transcutaneous electrical acustimulation (TEA) by replacing needles with surface electrodes and testing acupoints that target peripheral nerves. Based on prior mechanistic and clinical studies, two stimulation parameters and effective acupoints will be tested. In the UG3 phase, the TEA device and a cell phone app will be optimized for use in IBS abdominal pain, and an acute clinical study will determine the best stimulation locations and parameters. During the UH3 phase, an early feasibility clinical study will be performed in 160 IBS patients in treating abdominal pain. Participants will self-administer the therapy at home/work and will be randomized across four treatment groups to determine the therapeutic potential of the TEA system.

NOFO Title: HEAL Initiative: Translating Research to Practice to End the Overdose Crisis (R61/R33 Clinical Trial Optional)
NOFO Number: RFA-DA-23-053
Summary:

Significant racial, ethnic, socioeconomic, and geographic disparities affect access to opioid use disorder (OUD) treatment and have thus contributed to the opioid overdose crisis. Patient navigator interventions after hospitalization can improve access to treatment, but challenges prevent full adoption of these strategies. These include lack of coordination across institutions, inadequate data sharing, workforce shortages, and lack of awareness, especially in resource-limited communities. This project aims to develop a hospital system-wide patient navigation protocol that can be scaled up to address OUD treatment linkage and continuity after hospitalization.