EPPIC-Net: Platform Protocol to Assess Treatments for Painful Diabetic Peripheral Neuropathy

NCT05476276 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: 2022P002381 (EN21-PP)5U24NS113850-03
• Study Type: interventional
• Target: 127
• Locations: 1 country
• Sites: 23

Brief Summary

This is a Platform Protocol to perform Phase II clinical trials in The Early Phase Pain Investigation Clinical Network (EPPIC-Net), under The Helping to End Addiction Long-termSM Initiative, or NIH HEAL InitiativeSM, related to the treatment of Painful Diabetic Peripheral Neuropathy (PDPN) in a platform setting to test multiple assets under a single protocol.

Conditions

Painful Diabetic Neuropathy

Outcome Measures

Primary Outcomes (1)

• Daily 0-10 pain NRS

  Typically, the primary efficacy endpoint for this Platform Protocol will be based on the daily 0-10 pain NRS. Participants will respond to the following every evening before going to bed: * "Select the number that best describes your average neuropathy pain during the past 24 hours." * "Select the number that best describes your worst neuropathy pain during the past 24 hours." Typically, the primary efficacy endpoint for this Platform Protocol will be based on the daily 0-10 pain NRS. Participants will respond to the following every evening before going to bed: * "Select the number that best describes your average neuropathy pain during the past 24 hours." * "Select the number that best describes your worst neuropathy pain during the past 24 hours."

  Past 24 hours

Secondary Outcomes (10)

• Pain, Enjoyment, and General activity scale (PEG)

  Past 24 hours

• Pain Catastrophizing Scale - Short Form 6 (PCS-SF6)

  Past 24 hours

• PROMIS Physical Functioning Short-Form 6b

  Past 24 hours

• Pain Health Questionnaire (PHQ-2)

  Past 24 hours

• Generalized Anxiety Disorder - 2 item scale (GAD-2)

  Past 24 hours

Other Outcomes (2)

• Norfolk Quality of Life - Diabetic Neuropathy (Norfolk QOL-DN)

  Past 24 hours

• Neuropathy Examination

  Past 24 hours

Study Arms (2)

EN21-01 ISA

EXPERIMENTAL

The EN21-01 Intervention Specific Analysis is detailed in the protocol (NCT#)

Drug: ISA specific

Placebo Comparator

PLACEBO COMPARATOR

Each ISA will detail the use of the Placebo Comparator.

Drug: ISA specific

Interventions

ISA specific DRUG

ISA specific interventions will be listed in their protocols.

EN21-01 ISA; Placebo Comparator

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to provide informed consent. Legally Authorized Representatives (LARs) are not allowed, but impartial witnesses may be utilized as needed for visually impaired participants.
• years of age and older
• Diagnosis of diabetes mellitus
• Meets the Toronto Criteria for probable clinical sensorimotor polyneuropathy, with PDPN symptoms present for at least six months. This is defined as a combination of symptoms and signs with any two or more of the following (must be present bilaterally in the distal lower extremities): neuropathic symptoms, decreased distal sensation, or unequivocally decreased (or absent) ankle reflexes. Specifically:
• The presence of any neuropathic symptoms on either the "Douleur Neuropathique en 4 Questions" (DN4) or the EPPIC-Net Neuropathy Exam will suffice to demonstrate "neuropathic symptoms."
• Decreased distal sensation is satisfied by any of the following:
• i. "Yes" is checked at least once under Question 3 of the DN4 which queries hypoesthesia to touch and pinprick.
• ii. At least one score of "reduced" or "absent" on the right AND at least one score of "reduced" or "absent" on the left in any of the following items from the EPPIC-Net Neuropathy Exam:
• Pin sensation in segments 1 or 2 (i.e. the toes and feet)
• Vibration at the great toe
• Joint position at the great toe
• Light touch/touch pressure at the great toe
• Temperature at the great toe
• Monofilament at the great toe c. Decreased or absent ankle reflexes is satisfied by a score of "reduced" or "absent" on the right AND left in the "Ankle reflex" item in the EPPIC-Net Neuropathy Exam.
• A score of at least 4 on the "Douleur Neuropathique en 4 Questions" (DN4).

You may not qualify if:

• Peripheral neuropathy that is known to have been caused by a condition other than diabetes (e.g. HIV, cancer/chemotherapy-induced, other medication-induced, alcohol-induced, hereditary, autoimmune neuropathies, uncontrolled or untreated hypothyroidism). Note that participants will not be tested for HIV, this will be established by patient report or review of the medical record.
• Other significant pain conditions involving the same area as the neuropathy (e.g. physical deformity of the feet, plantar fasciitis, lumbosacral radiculopathy with distal lower extremity pain, fibromyalgia involving the lower limbs, Morton's neuroma), that in the opinion of the investigator would interfere with the participant's ability to rate the neuropathy pain.
• Other pain conditions not involving the same area as the neuropathy which (in the opinion of the investigator) interfere with the participant's ability to rate the neuropathy pain.
• Any amputation of the lower limb which interferes with the participant's ability to rate the neuropathy pain. If there is any amputation please contact the MM to confirm eligibility prior to randomization to an ISA.
• The presence of any current foot ulcer.
• Significant peripheral vascular disease defined as symptoms consistent with intermittent claudication.
• Use of other investigational drugs within 3 months before screening and throughout the study.
• Known or suspected hypersensitivity to all of the assets (active component and excipients) currently being tested in the Platform Protocol.
• Undergone neurolytic or neurosurgical therapy or used an implanted neurostimulating device for neuropathic pain in the distal lower limbs within 3 months of screening.
• Use of the high dose capsaicin patch (8%) in the 6 months before screening and throughout the study (for the treatment of PDPN). Use of the capsaicin patch in a manner that is not expected to interfere with the measurement of PDPN severity is allowed.
• Participants who meet any of the following regarding concomitant treatments:
• Unwilling or unable to discontinue episodic or periodic treatments for pain in the distal legs and/or feet (e.g., injections of local anesthetics).
• Starting a new non-pharmacological pain treatment (e.g. relaxation/hypnosis, physical or occupational therapy, any exercise-based therapy, any talk-based therapy, acupuncture, TENS) for the treatment of PDPN within 4 weeks prior to screening OR planning on starting a new non-pharmacologic treatment for PDPN OR planned changes to a stable non-pharmacologic treatment for PDPN during the study.
• i. Non-pharmacological treatment for conditions other than PDPN is allowed without restriction.
• Active use of opioids or marijuana for any reason at screening and unwilling or unable to discontinue use.

Sponsors & Collaborators

• James P. Rathmell, MD: lead
• New York University: collaborator
• Icahn School of Medicine at Mount Sinai: collaborator
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (23)

University of California, San Diego

San Diego, California, 92037, United States

Location

South Lake Pain Institute

Clermont, Florida, 34711, United States

Location

SIMEDHealth LLC

Gainesville, Florida, 32607, United States

Location

University of Florida

Gainesville, Florida, 32611, United States

Location

Northwestern Department of Neurology

Chicago, Illinois, 60611, United States

Location

Healthcare Research Network (Flossmoor)

Flossmoor, Illinois, 60422, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

University of Maryland - Baltimore

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21205, United States

Location

MGH Department of Anesthesia, Critical Care, and Pain

Boston, Massachusetts, 02114, United States

Location

Healthcare Research Network (Hazelwood)

Hazelwood, Missouri, 63042, United States

Location

Columbia University Medical Center/Neurological Institute

New York, New York, 10032, United States

Location

Mount Sinai School of Medicine

New York, New York, 10451, United States

Location

University of Rochester

Rochester, New York, 14627, United States

Location

Clinical Inquest Center

Beavercreek, Ohio, 45431, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15206, United States

Location

Low Country Pain Center

Orangeburg, South Carolina, 29118, United States

Location

Nerve and Muscle Center of Texas

Houston, Texas, 77030, United States

Location

University of Utah School of Medicine

Salt Lake City, Utah, 84132, United States

Location

Eastern Virginia Medical School

Norfolk, Virginia, 23510, United States

Location

VCU Department of Neurology

Richmond, Virginia, 23298, United States

Location

University of Washington

Seattle, Washington, 32611, United States

Location

University of Wisconsin

Madison, Wisconsin, 53706, United States

Location

MeSH Terms

Conditions

Diabetic Neuropathies

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases

Study Officials

• Jessica Robinson-Papp, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Randomization assignment within an ISA will be blinded from study participants, staff from clinical sites, investigators, asset owners, IND sponsors, and/or designees. This blinding will be accomplished by providing identical investigational product and packaging for each asset and its corresponding control treatment. The use of IXRS will ensure the blinding is accomplished.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chair, Department of Anesthesiology, Perioperative and Pain Medicine

Model Details: The Platform Protocol is intended to potentially accommodate different design plans for different assets. In addition, it is anticipated that the protocol may evolve over time, as lessons learned from earlier assets are used to fine tune the study design for later assets in an adaptive approach. For reasons of generalizability (including consideration of minimizing participant burden and being attractive to asset holders), a parallel-group design will typically be employed, and it is the current intention that designs should provide 80% power to detect an effect size of 0.35 on the primary efficacy outcome

Study Record Dates

• First Submitted: July 25, 2022
• First Posted: July 27, 2022
• Study Start: September 21, 2022
• Primary Completion: August 28, 2025
• Study Completion: August 28, 2025
• Last Updated: March 19, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (23)