Early Phase Pain Investigation Clinical Network (EPPIC-Net)


The Research Need

The Early Phase Pain Investigation Clinical Network (EPPIC-Net) seeks to enhance the treatment of acute and chronic pain and reduce reliance on opioids by accelerating early-phase clinical trials of non-addictive treatments for pain.

About the Program

EPPIC-Net has the capacity to quickly and efficiently conduct many simultaneous multisite studies. The network will conduct studies on a variety of treatments, including drugs and devices, as well as studies to better understand pain.

EPPIC-Net will:

  • Test new pain treatments (e.g., small molecules, biologics, devices) with go/no-go criteria in early-stage trials to move toward efficacy trials for regulatory approval.
  • Provide proof-of-concept clinical testing of potential biomarkers and new treatments to help identify specific pathways or mechanisms that hold promise for future therapeutic development.
  • Validate biomarkers for utility in assessing target engagement or pain outcomes that could be used to accelerate development of new, non-addictive pain therapies.
  • Develop and test innovative clinical trial paradigms to evaluate pain therapies.
  • Establish well-characterized patient cohorts with specific pain conditions and clearly defined outcome measures for early-stage trials.
  • Continuously learn from experience to engineer adaptive, ever-improving early-phase testing of new pain therapies.

EPPIC-Net supports clinical trials focused on:

  • Investigational drugs and biologics, investigational devices, natural products, and surgical procedures for the treatment of pain.
  • Deeply phenotyped patients with pain conditions of high unmet need.
  • Drugs or devices with strong potential to move to industry-funded Phase 3 efficacy trials, should the early-phase study achieve the prespecified endpoints.

EPPIC-Net interfaces with the National Institute of Arthritis and Musculoskeletal and Skin Diseases’ Back Pain Consortium (BACPAC) Research Program to study how people with different types of back pain respond to specific interventions.

Learn more about how the Helping to End Addiction Long-term® Initiative, or NIH HEAL Initiative® is involved in BACPAC.

Open Funding Opportunities

There are no Open Funding Opportunities at this time.

Program Details

To date, through the NIH HEAL Initiative, NIH has funded two trials and 14 grants to support the infrastructure network for this program, totaling $52.3 million.

The network includes 12 Specialized Clinical Centers, each with multiple sites. It also includes two centers that will provide supportive infrastructure.

  • The Specialized Clinical Centers (hubs) are connected with a large number of pain patients who can be recruited for participation in trials, including children, people over age 65, veterans, patients involved with different subspecialties (e.g., dentistry, gynecology, oncology, urology), and people of various races and ethnicities. The hubs conduct the research procedures.
  • The Clinical Coordinating Center (CCC) will provide scientific leadership for the design and conduct of clinical studies. The CCC will also provide support on methods, organization, and logistics for the multicenter trials conducted within EPPIC-Net.
  • The Data Coordinating Center (DCC) will manage data and biospecimens from the trials conducted in EPPIC-Net and other parts of the NIH HEAL Initiative’s pain research program. The DCC will make these data and biospecimens available to pain researchers. It will also provide expertise and leadership on statistical design and analysis of studies conducted within EPPIC-Net.

Research Examples

The awards support a network to advance new treatments for pain by conducting early-phase clinical trials with adults and children. Currently funded trials include:

  • In EPPIC-Net’s first Phase 2 clinical trial, researchers will test the novel oral drug CNTX-6970 in patients who experience moderate to severe knee osteoarthritis pain. Preclinical studies of CNTX-6970 have demonstrated potent analgesia in multiple pain models.
  • Currently one EPPIC-Net clinical trial is underway to address diabetic neuropathy. Many patients with diabetic peripheral neuropathy find the sensory loss itself uncomfortable; however, some patients report pain due to their diabetic peripheral neuropathy, referred to as painful diabetic peripheral neuropathy. Despite the availability of off-label treatment options, many patients with diabetic peripheral neuropathy still experience significant pain, and thus more effective, non-addictive options are needed.
    • One EPPIC-Net trial will further development of NRD135S.E1, an oral analgesic therapeutic candidate which has been well tolerated and shown clinically relevant benefit in early clinical studies.

Specialized Clinical Centers

  • Duke University – North Carolina
  • Icahn School of Medicine at Mount Sinai – New York
  • Massachusetts General Hospital – Massachusetts
  • Medical College of Wisconsin – Wisconsin
  • Medical University of South Carolina – South Carolina
  • New York University School of Medicine – New York
  • University of California, San Diego – California
  • University of Florida – Florida
  • University of Pennsylvania – Pennsylvania
  • University of Pittsburgh at Pittsburgh – Pennsylvania
  • University of Rochester – New York
  • University of Washington – Washington

Clinical Coordinating Center

  • Massachusetts General Hospital – Massachusetts

Data Coordinating Center

  • New York University School of Medicine – New York

Funded Projects

Oct 11, 2021
A 24-week Week Study to Evaluate the Safety and Efficacy of CNTX-6970 in Subjects with Moderate to Severe Knee Osteoarthritis Pain.
Oct 08, 2021
Sep 25, 2021
University of Rochester Hub and Spokes for the EPPIC Network - Specialized Clinical Center
Sep 25, 2021
Administrative Supplement to Support Strategies to Increase Participant Diversity, Inclusion and Engagement in EPPIC NET
Sep 25, 2021

Closed Funding Opportunities

HEAL Initiative: Early Phase Pain Investigation Clinical Network - Specialized Clinical Centers (U24 Clinical Trial Not Allowed)
Sep 25, 2019
HEAL Initiative: EPPIC-Net Pain Research - Application for Clinical Trial and Related Activities (OT2) [ROLLING SUBMISSION ACCEPTED: BY INVITATION ONLY]
Jun 03, 2022
HEAL Initiative: EPPIC-Net Pain Research Asset Application – Dossier (OT1) [ROLLING SUBMISSION ACCEPTED: BY INVITATION ONLY]
Jun 03, 2022


EPPIC-Net is NOT currently accepting new applications. Announcements regarding updates to the EPPIC-Net application process and any other relevant HEAL funding opportunities will be posted here as they become available.