Funded Projects

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:

Social determinants of heath may affect breast cancer diagnosis and disease staging at time of mastectomy. It is unclear if socioeconomic factors such as annual income, marital status/single parent household, number of children, distance from the hospital, and other life stressors facing individuals from under-resourced populations affect development of postmastectomy pain syndrome or response to the drug ketamine. This research will analyze these factors toward mitigating post-mastectomy pain. This analysis will also serve as the basis for further research to define pathways that minimize health disparities plays in the development of chronic, post-surgical pain. The ultimate goal of this research is to normalize risk for chronic pain after breast surgery.

 

NOFO Title: HEAL Initiative: Integrated Approach to Pain and Opioid Use in Hemodialysis Patients: The Hemodialysis Opioid Prescription Effort (HOPE) Consortium - Clinical Centers (U01 Clinical Trial Required)
NOFO Number: RFA-DK-18-030
Summary:

In this study, 600 to 700 hemodialysis patients receiving chronic opioids will be randomized across the Hemodialysis Opioid Prescription Effort (HOPE) Consortium to enhanced treatment as usual, buprenorphine therapy, or buprenorphine plus mindfulness-based cognitive therapy intervention delivered by telephone and adapted for pain (MBCT-TP). The following specific aims will be assessed: Aim 1—to assess the effectiveness of buprenorphine in reducing chronic opioid use and prescriptions in hemodialysis patients on opioids at baseline, compared with an enhanced treatment as usual intervention and to assess the effectiveness of buprenorphine in improving pain intensity, quality of life measures, and hospitalizations; Aim 2—to assess the incremental effectiveness of MBCT-TP added to buprenorphine compared with buprenorphine alone on pain interference with physical, social, and mental functioning, opioid use, pain intensity, other quality of life measures, hospitalizations, and mortality.

NOFO Title: HEAL Initiative: Discovery and Validation of Novel Targets for Safe and Effective Pain Treatment (R01 Clinical Trial Not Allowed)
NOFO Number: NS22-034
Summary:

Oral cancers are painful and often require use of opioid medications to manage pain. However, the effectiveness of opioids often wanes quickly, and many patients require higher doses because they develop tolerance to these medications. This project will study the potential value of blocking epidermal growth-factor receptors interacting with peripheral nerves to treat oral cancer pain. The findings will advance understanding of the molecular mechanisms underlying oral cancer pain and provide a rationale for repurposing epidermal growth-factor receptor blockers, which is already approved for head and neck cancer treatment for treating oral cancer and associated pain.

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:

Voltage-gated sodium channels are responsible for the transmission of pain signals. Nine genes have been identified, each having unique properties and tissue distribution patterns. Genetic studies have correlated a hereditary loss-of-function mutation in one human Na+ channel isoform – ?Na?V?1.7 – with a rare genetic disorder known as Congenital Insensitivity to Pain (CIP). Individuals with CIP are not able to feel pain without any significant secondary alteration. Thus, selective inhibition of ?Na?V?1.7 in normal humans could recapitulate the phenotype of CIP. This research team developed a non-permanent gene therapy to target pain that is non-addictive (because it targets a non-opioid pathway), highly specific (only targeting the gene of interest), and long-term lasting (around 3 weeks in preliminary assays in mice). During this Phase I , the team will 1) test additional pain targets ?in vitro?, and 2) evaluate the new targets ?in vivo ?in mice models of inflammatory and neuropathic pain. 

NOFO Title: HEAL Initiative: Translational Devices to Treat Pain (U44 Clinical Trial Optional)
NOFO Number: RFA-NS-19-017
Summary:

The research team will develop HD64—a high-resolution, 64-channel spinal cord stimulation therapy to provide more pain relief for those suffering from chronic neuropathic pain and opioid dependence. HD64 provides an ultra-thin conformal blanket of stimulation contacts across the width of the spinal cord and enables more precise targeting of the lateral structures of the spinal cord to enhance pain relief. A cadaveric pilot run followed by a non-significant risk intraoperative study will be performed to inform the design parameters of HD64 arrays. The study will evaluate activation of medial and lateral spinal targets. At the end of Phase 1, the clinical feasibility of HD64 surgical leads will be established. In Phase 2, researchers will develop an external active lead pulse generator and charger. They will perform an early feasibility study human trial using active HD64 and mechanical and electrical design verification testing and chronic safety studies in large animals.

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 seeks to develop a high-resolution spinal cord stimulation therapy for treating chronic neuropathic pain of the lower extremities, groin, and lower back. Systems that use wireless communication methods require robust strategies to prevent various forms of cyberattacks on implantable devices. The focus of this project's research will be to develop a new cybersecurity risk-reduced architecture for Bluetooth low-energy implant communication.

NOFO Title: Discovery of Biomarkers, Biomarker Signatures, and Endpoints for Pain (R61/R33 Clinical Trial Optional)
NOFO Number: RFA-NS-18-041
Summary:

Debilitating pain is the most common complication of sickle cell disease (SCD), but there is significant variability in pain expression in these patients. Currently, there is no plasma biomarker that can prognosticate which patients are likely to experience pain. The overall goal of this proposed research is to develop a biomarker that prognosticates the clinical expression of pain in SCD. Project aims are to (1) derive the inflammatory index for pain by identifying inflammatory and immune regulatory gene probe sets that will distinguish healthy controls, patients with SCD in baseline health, and patients with SCD in acute pain and (2) determine whether co-expressed genes from patients with SCD correlate with clinical pain data. Subsequent aims are to (1) determine the clinically meaningful changes of the index in patients with SCD and (2) investigate the preliminary clinical validity of the index as a prognostic biomarker for pain in patients with SCD.

NOFO Title: HEAL Initiative: Pragmatic and Implementation Studies for the Management of Pain to Reduce Opioid Prescribing (PRISM)(UG3/UH3 Clinical Trial Optional)
NOFO Number: RFA-AT-19-004
Summary:

Prescriptions for narcotic pain relief after surgery result in unintended prolonged opioid use for hundreds of thousands of Americans. Nonpharmacological pain care is effective and recommended by guidelines for perioperative pain while offering a more favorable risk-benefit ratio. However, nonpharmacological pain care is rarely used as first or second-line therapy after surgery. Patient and clinician decision support interventions are effective in encouraging patient-centered and guideline-concordant care, but these strategies have not been tested pragmatically as a bundle in everyday postoperative pain care. The NOHARM trial will first confirm the feasibility of patient-facing and clinician-facing decision support components of an EHR-embedded evidence-based bundle. The investigators will test the bundle in a stepped-wedge cluster randomized trial. They will test a sustainable system strategy that could change the paradigm of perioperative pain management toward nonpharmacological options in a manner that preserves patient function, honors patient values, and maintains availability of opioids as a last resort.

NOFO Title: Discovery of Biomarkers, Biomarker Signatures, and Endpoints for Pain (R61/R33 Clinical Trial Optional)
NOFO Number: RFA-NS-18-041
Summary:

There is currently no recognized way of accurately predicting who will recover from post-traumatic headache (PTH) during the acute phase following concussion and who will go on to develop persistent post-traumatic headache (PPTH), a condition that is difficult to treat effectively. Clinical experience suggests that early treatment is most effective, before headache patterns become persistent, but treating all patients with PTH would expose some patients to unnecessary treatment. Clinicians lack the information needed to make informed treatment decisions. Therefore, the study goals are to develop a prognostic biomarker signature for PPTH using clinical data and structural and functional brain neuroimaging and to assess the predictive accuracy of an ensemble biomarker signature for the early identification of patients at high risk for PPTH. This study can be translated into clinical practice and integrated into PTH clinical trials for early identification of those individuals who are at high risk for PPTH.

NOFO Title: HEAL Initiative: EPPIC-Net Pain Research Asset Application (OT2)
NOFO Number: OTA-20-008
Summary:

This award funds EPPIC-NET’s first phase 2 clinical trial, testing the novel oral drug CNTX-6970 in patients with moderate to severe knee osteoarthritis pain. It will include 150 participants at EPPIC-Net sites across the United States. Preclinical studies of CNTX-6970, which binds effectively and dose-proportionally to C-C chemokine type 2 (CCR2) receptors, have demonstrated potent analgesia in multiple pain models, with no emergent safety issues. CNTX-6970 has effects both at an affected joint, as well as on neural signaling. Participants will be randomized to receive CNTX-6970, placebo, or a third pain medication and will be followed for 24 weeks.

NOFO Title: HEAL Initiative: Early Phase Pain Investigation Clinical Network - Specialized Clinical Centers (U24 Clinical Trial Not Allowed)
NOFO Number: NS115689-01
Summary:

The MGH EPPIC-Net hub will utilize two well-established collaborative entities in both patient care and clinical research at the Massachusetts General Hospital (MGH): 1) MGH Division of Pain Medicine and 2) MGH Center for Translational Pain Research. This hub-spoke network at MGH will include four core spokes consisting of both academic centers and community health care organizations, as well as over a dozen spokes that can be recruited as needed based on special requirements of phase II trials and research studies. The responsibilities of this hub-spoke network at MGH include a) coordinating phase II trials/clinical biomarker validation studies; b) recruiting well-phenotyped subjects in a timely manner; c) collecting clinical data and targeted outcome data tailored to meet the needs of each clinical trial/study; and d) maintaining communications within and outside the hub, including the NIH EPPIC-Net.

NOFO Title: HEAL Initiative: Integrated Approach to Pain and Opioid Use in Hemodialysis Patients: The Hemodialysis Opioid Prescription Effort (HOPE) Consortium - Clinical Centers (U01 Clinical Trial Required)
NOFO Number: RFA-DK-18-030
Summary:

Because pain is a multidimensional phenomenon with physical and psychosocial components, a pain management approach relying solely on analgesics is unlikely to be efficacious. Nonpharmacologic therapies for co-occurring chronic pain and opioid use in hemodialysis patients should target and alter cognitive-affective circuits that govern responses elicited by pain, stress, mood disorders, and opioid-related cues. These domains are directly addressed through the behavioral therapy program known as MORE (Mindfulness-Oriented Recovery Enhancement)—a multipronged mindfulness-oriented individualized group therapy that integrates mindfulness training, cognitive reappraisal, and enhancement of natural reward processing. The specific aims are 1) to determine the impact of MORE on chronic pain and opioid use in hemodialysis patients and 2) to determine predictors of chronic pain, opioid use, and response to MORE.

NOFO Title: HEAL Initiative: Early Phase Pain Investigation Clinical Network - Clinical Coordinating Center (U24 Clinical Trials Not Allowed)
NOFO Number: RFA-NS-19-023
Summary:

The objective of the Early Phase Pain Investigation Clinical Network (EPPIC-Net) and EPPIC- Net initiatives is to rapidly and efficiently translate advances in the neurobiology of pain into treatments for people with chronic and acute pain, conditions associated with a significant burden to both patients and society. The Clinical Coordinating Center (CCC) for EPPIC-Net will promote and facilitate, from initial conception through final analysis, clinical trials in adult and pediatric populations with acute or chronic pain by providing efficient methodological, organizational, and logistical support. The EPPIC-Net-CCC will adopt and establish processes aimed at dramatically increasing the efficiency of multicenter clinical trials, improving the overall quality of clinical trials, promoting patient recruitment and retention as well as increasing the number of clinical investigators and research staff well trained and passionate about leading and conducting multicenter clinical trials.