Funded Projects

NOFO Title: HEAL Initiative: Pragmatic and Implementation Studies for the Management of Pain to Reduce Opioid Prescribing (PRISM) (UG3/UH3, Clinical Trials Optional)
NOFO Number: RFA-AT-20-004
Summary:

In the US, approximately 100,000 people, mainly of African and Hispanic background have Sickle Cell Disease (SCD). Pain is a constant companion and chronic disabling symptom for those with SCD. It is increasingly clear that adults with chronic SCD pain also experience periods of acute worsening of their pain. The evaluation of nonpharmacological therapies that reduce chronic pain and the need for opioid medication among individuals with SCD is critically needed to address lack of adequate pain control to prevent periods of acute deterioration and high opioid use with negative sequelae. The investigators will conduct a hybrid type 1 effectiveness-implementation trial to assess the effectiveness of acupuncture and guided relaxation in patients with SCD while observing and gathering information on implementation in three health systems. The study will utilize a 3-arm, 3-site pragmatic randomized controlled SMART trial design that evaluates adaptive interventions, in which selection of interventions responds to patients? characteristics and evolving clinical status. The investigators will use the Consolidated Framework for Implementation Research to plan, execute, and evaluate implementation processes.

NOFO Title: Notice of Special Interest for HEAL Initiative: Request for Administrative Supplements to Existing Grants for Identification and Validation of New Pain and Opioid Use Disorder Targets within the Understudied Druggable Genome
NOFO Number: NOT-TR-20-008
Summary:

Opioids and other addictive substances have powerful rewarding properties that drive the development of addiction. They also have aversive properties that motivate their avoidance and protect against addiction. This project will explore the role of Type 2 Taste Receptor proteins (Tas2Rs or T2Rs) in regulating the aversive properties of opioids, potentially establishing an entirely new class of receptors that can be targeted for the development of novel addiction therapeutics.

NOFO Title: HEAL Initiative: Notice of Special Interest (NOSI) regarding the Availability of Administrative Supplements to Support Strategies to Reduce Stigma in Pain Management and Opioid Use Disorder (OUD) and Treatment
NOFO Number: NOT-OD-20-101
Summary:

Patients with chronic low back pain, often have depressive and anxiety symptoms and use opioids all of which are associated with stigma. In turn stigma leads to decreased treatment seeking and adherence, increased depression and pain, and poor treatment outcomes. Intersection of these health-related stigmas may have synergistic effects. This study aims to enhance the findings of a clinical trial to test antidepressant medication and Enhanced Fear Avoidance Rehabilitation in patients with chronic low back pain and high levels of depression and anxiety. The effects of these intersecting types of stigma on the efficacy of the interventions will be evaluated to better understand the needs of the patient population and to inform development of a stigma reducing intervention that can be implemented care providers.

NOFO Title: Notice of Special Interest: HEAL Supplements to Improve the Treatment and Management of Common Co-occurring Conditions and Suicide Risk in People Affected by the Opioid Crisis
NOFO Number: NOT-MH-20-025
Summary:

People with opioid use disorder (OUD) are at increased risk of depression and other mental health conditions, and a significant proportion of opioid-related deaths are likely suicides. Nearly 50% of patients who die by suicide make a healthcare visit in the month prior, most often to primary care. Yet systematic screening of patients with OUD for suicide risk is rarely done. Clinical decision support tools within the electronic health record can improve healthcare prevention measures and important clinical outcomes. This primary care-based clinic-randomized trial will integrate a clinical decision support tool for suicide risk prediction with a clinical decision support tool for the identification, diagnosis, and treatment of opioid use disorder. By integrating these two tools, the study will identify patients with opioid use disorder who have increased risk for suicide, ultimately increasing engagement in both OUD treatment and outpatient mental health care

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:

Osteoarthritis (OA) is the most common form of arthritis and a leading cause of pain and disability. Current challenges of managing OA are that there is no OA disease-modifying drug available, there are few effective treatment strategies, and there is an over-reliance on the use of opioids to manage OA-related joint pain. This project aims to validate vascular endothelial growth factor receptors 1 and 2 (VEGFR 1 receptor = Flt1) and (VEGFR 2 receptor = Flk1) as novel therapeutic targets for OA. This is based on a hypothesis that blocking these two specific receptors of VEGF will inhibit cartilage tissue degeneration and alleviate pain symptoms. This study will test the role of VEGFR-1 and -2 in multiple OA animal models using multiple available VEGF inhibitor molecules. The findings from these studies will develop a rationale for future clinical trials to target VEGFR-1 and -2 for OA patients and develop a novel non-addictive treatment for both joint pain and OA pathology.

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:

Over 2 million Americans have an Opioid Use Disorder (OUD) and the risks associated with misuse of opioids have prompted a public health crisis. There are three effective FDA-approved drugs for medication assisted treatment (MAT) of OUD. However, while MAT can reduce overall OUD related mortality by as much as fifty percent, relapse and treatment discontinuation are common within the first 5 to 12 weeks of MAT. As longer treatment retention is correlated with better long-term outcomes, the development of an adjunctive medication to alleviate key psychiatric symptoms associated with treatment failure would address an important unmet need. This study seeks to evaluate the safety and efficacy of brexpiprazole as adjunctive treatment to buprenorphine/naloxone in OUD. If successful, this study could enhance the effectiveness of OUD treatments by extending the duration of treatment, thereby reducing the likelihood for relapse and overdose.

NOFO Title: Notice of Special Interest for HEAL Initiative: Request for Administrative Supplements to Existing Grants for Identification and Validation of New Pain and Opioid Use Disorder Targets within the Understudied Druggable Genome
NOFO Number: NOT-TR-20-008
Summary:

Neuropathic pain conditions are difficult to treat, and novel non-narcotic analgesics are desperately needed. The G protein-coupled receptor 160 (GPR160) has emerged as a novel target for analgesic development, as GPR160 in the spinal cord may play a role in the transition from acute to chronic pain. Cocaine- and Amphetamine-Regulated transcript peptide (CARTp) was identified as a ligand for GPR160. Blocking endogenous CARTp signaling in the spinal cord attenuates neuropathic pain, whereas intrathecal injection of CARTp evokes painful hypersensitivity in rodents through GPR160-dependent extracellular signal-regulated kinase (ERK) and cyclic AMP response element-binding pathways (CREB). This project will isolate and biochemically characterize GPR160 and establish methods for biochemical characterization of GPR160 interaction with CARTp activator. Researchers will miniaturize and optimize biochemical assay and scale up protein production for future high throughput biochemical screening to identify potent inhibitors of GPR160 activation. These studies are critical for defining the molecular mechanism of CARTp/GPR160 interactions and initiating large-scale screens for new inhibitors to develop novel therapeutics.

NOFO Title: Notice of Special Interest to Encourage Eligible NIH HEAL Initiative Awardees to Apply for Administrative Supplements to Promote Training in Clinical Research on Pain (Admin Supp ? Clinical Trial Not Allowed)
NOFO Number: NOT-NS-20-044
Summary:

There are numerous non-pharmacological interventions for chronic low back pain, yet no treatment is invariably effective for all. Understanding patient characteristics that predict differential responses to these non-pharmacological interventions will allow for tailored treatments to maximize positive patient impact. This supplement supports a training experience for an individual in clinical pain research, including exploring differential response to psychotherapeutic interventions. The aim of the project is to provide an extensive systematic literature review examining baseline phenotypic factors that predict differential responsiveness to the some of the most commonly used psychotherapeutic interventions for chronic low back pain.

NOFO Title: Notice of Special Interest: HEAL Supplements to Improve the Treatment and Management of Common Co-occurring Conditions and Suicide Risk in People Affected by the Opioid Crisis
NOFO Number: NOT-MH-20-025
Summary:

Paralleling overall population trends, opioid use has escalated among pregnant and postpartum women, particularly among those with co-occurring perinatal mood and anxiety disorders, yet treatment remains underutilized. Since 2008, health insurance coverage changes led to a dramatic expansion of behavioral health coverage by increasing coverage and extending federal parity protections to more than 60 million Americans. Characterizing the clinical and economic impacts of these unprecedented extensions of behavioral coverage on maternal and infant outcomes among women with perinatal opioid use, chronic pain, and suicidality with and without co-occurring perinatal mood and anxiety disorders will inform future policy and targeted 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:

Many non-opioid drugs target G Protein-Coupled Receptors (GPCRs), a family of proteins involved in many pathophysiological processes including pain, fail during clinical trials for unknown reasons. A recent study found GPCRs not only function at the surface of nerve cells but also within a cell compartment called the endosome, where their sustained activity drives pain. This study will build upon this finding and test whether the clinical failure of drugs targeting plasma membrane GPCRs is related to their inability to target and engage endomsomal GPCRs (eGPCRs). This study will use stimulus-responsive nanoparticles (NP) to encapsulate non-opioid drugs and selectively target eGPCR dyads to investigate how eGCPRs generate and regulate sustained pain signals in neuronal subcellular compartments. This study will also validate eGCPRs as therapeutic targets for treatment of chronic inflammatory, neuropathic and cancer pain. Using NPs to deliver non-opioid drugs, individually or in combinations, directly into specific compartments in nerve cells could be a potential strategy for new pain therapies.

NOFO Title: HEAL Initiative: Pain Management Effectiveness Research Network: Clinical Trial Planning and Implementation Cooperative Agreement (UG3/UH3 Clinical Trial Required)
NOFO Number: RFA-NS-19-021
Summary:

Chronic musculoskeletal pain is common and often severe enough to be disabling. Some treatments such as cognitive behavioral therapies or analgesics may relieve pain for some, but not all patients. Combining effective therapies and providing support to ensure that patients are motivated to adhere to their treatment may prove to be more beneficial to patients than prescribing a drug or recommending a single non-pharmacological treatment. This study aims to evaluate a combination of complementary treatments and Registered Nurse (RN) support to motivate patients to use and maintain combined therapies. Some patients will receive phone-based motivational interviews with an RN to enhance their adherence to pain coping skills learned through web-based cognitive behavioral therapy in combination with duloxetine, a pain-relieving drug. Others will receive both treatments but will not receive support from an RN. The study aims to determine whether motivational nursing support enhances adherence to newly learned pain coping skills, and results in improved pain relief and physical function.

NOFO Title: Notice of Special Interest for HEAL Initiative: Request for Administrative Supplements to Existing Grants for Identification and Validation of New Pain and Opioid Use Disorder Targets within the Understudied Druggable Genome
NOFO Number: NOT-TR-20-008
Summary:

This project will establish a rapid research pipeline for linking plant-derived compounds to nociception (pain) and to G Protein-Coupled Receptors (GPCRs) and ion channels in the druggable human genome. As more than 80% of these membrane proteins are conserved in the C. elegans nematodes, the study will screen for compounds and genes affecting nociception as well as to identify novel ligand-receptor pairs using this model organism. The study will test which understudied GPCRs and ion channels are involved in nociception as well as attraction or repulsion behaviors. This research has the potential to reveal novel ligand-receptor pairs that could serve as new entry points for improved or alternative pain treatments.

NOFO Title: HEAL Initiative: Notice of Special Interest (NOSI) regarding the Availability of Administrative Supplements to Support Strategies to Reduce Stigma in Pain Management and Opioid Use Disorder (OUD) and Treatment
NOFO Number: NOT-OD-20-101
Summary:

Increasing primary care clinician intention and behavior to obtain waivers to prescribe buprenorphine for treatment of opioid use disorder and increase use of the Opioid Wizard, a clinical decision support tool, has potential for patient benefit. This supplement will provide support to evaluate a training tool as an intervention to reduce stigma in primary care clinics by integrating a stigma reduction training component into the Opioid Wizard training at multiple sites of the NIDA Clinical Trial Network. Primary care providers will be randomized to novel stigma reduction training, grounded in stigma science, or an attention-control training to determine whether stigma reduction training reduces provider stigma, increases intention to apply for a waiver to prescribe buprenorphine, and ultimately increase the likelihood that providers use Opioid Wizard. The proposed supplement will utilize the randomized controlled trial design embedded in the larger multisite trial to evaluate the Opioid Wizard tool to help primary care clinicians identify, diagnose, and treat patients with opioid use disorder while evaluating the effect of the stigma reduction training.