RECRUITING

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2022-09-21

Study Completion:2025-01-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05476276

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Able to provide informed consent. Legally Authorized Representatives (LARs) are not allowed, but impartial witnesses may be utilized as needed for visually impaired participants. 2. 18 years of age and older 3. Diagnosis of diabetes mellitus 4. 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: 1. 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." 2. Decreased distal sensation is satisfied by any of the following: * 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. 5. A score of at least 4 on the "Douleur Neuropathique en 4 Questions" (DN4). 6. Pain reporting during a pre-defined 7-day screening period meets study criteria (to be established using a centrally-administered screening algorithm) which may account for mean pain intensity reported, variability in reported values, and adherence in reporting. 7. Patient reported daily 11-point NRS (for average and worst pain over the last 24 hours) is completed on at least 5 out of the 7 days in the screening and baseline periods. 8. Participants must be willing and able to comply with scheduled visits, the treatment schedule, laboratory testing, and other requirements of the study (e.g., completion of app-based daily reporting). 9. Females may be included if they meet at least one of the following criteria (note that individual ISAs may specify more stringent measures to prevent pregnancy): 10. Specific requirements of male participants (regarding contraception) will be defined in the ISAs based on the potential toxicity profile of the asset. 3.2. Platform Protocol Exclusion Criteria (To be used in conjunction with ISA-specific criteria; note, some ISA criteria may be more stringent than Platform criteria; always follow the more stringent criteria when determining eligibility) 3.2.1. Neuropathy Confound Exclusion Criteria 1. 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. 2. 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. 3. 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. 4. 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. 5. The presence of any current foot ulcer. 6. Significant peripheral vascular disease defined as symptoms consistent with intermittent claudication. 3.2.2. Medication/Treatment Exclusion Criteria 7. Use of other investigational drugs within 3 months before screening and throughout the study. 8. Known or suspected hypersensitivity to all of the assets (active component and excipients) currently being tested in the Platform Protocol. 9. Undergone neurolytic or neurosurgical therapy or used an implanted neurostimulating device for neuropathic pain in the distal lower limbs within 3 months of screening. 10. 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. 11. Participants who meet any of the following regarding concomitant treatments: 1. Unwilling or unable to discontinue episodic or periodic treatments for pain in the distal legs and/or feet (e.g., injections of local anesthetics). 2. 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. 12. Active use of opioids or marijuana for any reason at screening and unwilling or unable to discontinue use. 3.2.3. Medical Exclusion Criteria 13. Clinically significant ECG or laboratory abnormalities at the Screening Visit that would put the participant at undue risk or affect the ability of the participant to participate in the trial (in the opinion of the investigator). Screening ECG and lab results may be repeated without requiring a rescreen, as long as the participant is still within the screening window. 14. Participants whose glycemic control has been unstable within 3 months before screening (e.g. ketoacidosis requiring hospitalization). 15. Proliferative retinopathy or maculopathy requiring acute treatment. 16. Requiring dialysis. 17. Myocardial infarction or stroke in the past 6 months. 18. Known diagnosis of moderate to severe hepatic impairment (equivalent to Child-Pugh class B or C) OR aspartate aminotransferase or alanine aminotransferase ≥ 3 times the upper limit of normal during the screening process. 19. A clinically significant illness or operative procedure within 4 weeks of screening. 20. Clinically significant surgery planned during the study period. If a surgery is planned, please contact the MM for approval before randomization. 21. History of malignancy or other medical condition that would put the participant at undue risk or affect the ability of the participant to participate in the trial (in the opinion of the investigator). 22. Pregnant or nursing. 3.2.4. Psychosocial and Substance Use Disorders Exclusion Criteria 23. A clinically significant psychiatric disease that would put the participant at undue risk or affect the ability of the participant to participate in the trial (in the opinion of the investigator). 24. Alcohol use disorder or other substance use disorders (other than nicotine or caffeine) in accordance with DSM-5 criteria within 12 months of screening. 25. Positive urine drug tests defined as one or more of the following (see Urine Drug Testing Section 6.2.13.5.1): 1. Two positive urine drug tests for a prescribed opioid (buprenorphine, opiates, methadone and/or oxycodone), prior to the initiation of investigational product (IP); 2. Two positive urine drug tests for marijuana (prescribed or recreational), prior to the initiation of investigational product (IP); 3. One positive urine drug test for cocaine, ecstasy, methamphetamines, or phencyclidine (PCP); 4. One positive urine drug test for non-prescribed amphetamines, barbiturates, benzodiazepines, or opioids (buprenorphine, opiates, methadone and/or oxycodone). 26. Vulnerable persons defined as either of the following: 1. Individuals whose willingness to volunteer in a clinical study may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation or of a retaliatory response from senior members of a hierarchy in case of refusal to participate.	Pregnancy or breastfeeding Severe psychiatric disorders Active substance abuse Unstable medical conditions Inability to comply with study requirements

Inclusion Criteria

Exclusion Criteria

1. Able to provide informed consent. Legally Authorized Representatives (LARs) are not allowed, but impartial witnesses may be utilized as needed for visually impaired participants.
2. 18 years of age and older
3. Diagnosis of diabetes mellitus
4. 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:
1. 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."
2. Decreased distal sensation is satisfied by any of the following:
* 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.
5. A score of at least 4 on the "Douleur Neuropathique en 4 Questions" (DN4).
6. Pain reporting during a pre-defined 7-day screening period meets study criteria (to be established using a centrally-administered screening algorithm) which may account for mean pain intensity reported, variability in reported values, and adherence in reporting.
7. Patient reported daily 11-point NRS (for average and worst pain over the last 24 hours) is completed on at least 5 out of the 7 days in the screening and baseline periods.
8. Participants must be willing and able to comply with scheduled visits, the treatment schedule, laboratory testing, and other requirements of the study (e.g., completion of app-based daily reporting).
9. Females may be included if they meet at least one of the following criteria (note that individual ISAs may specify more stringent measures to prevent pregnancy):
10. Specific requirements of male participants (regarding contraception) will be defined in the ISAs based on the potential toxicity profile of the asset.
3.2. Platform Protocol Exclusion Criteria (To be used in conjunction with ISA-specific criteria; note, some ISA criteria may be more stringent than Platform criteria; always follow the more stringent criteria when determining eligibility)
3.2.1. Neuropathy Confound Exclusion Criteria
1. 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.
2. 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.
3. 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.
4. 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.
5. The presence of any current foot ulcer.
6. Significant peripheral vascular disease defined as symptoms consistent with intermittent claudication.
3.2.2. Medication/Treatment Exclusion Criteria
7. Use of other investigational drugs within 3 months before screening and throughout the study.
8. Known or suspected hypersensitivity to all of the assets (active component and excipients) currently being tested in the Platform Protocol.
9. Undergone neurolytic or neurosurgical therapy or used an implanted neurostimulating device for neuropathic pain in the distal lower limbs within 3 months of screening.
10. 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.
11. Participants who meet any of the following regarding concomitant treatments:
1. Unwilling or unable to discontinue episodic or periodic treatments for pain in the distal legs and/or feet (e.g., injections of local anesthetics).
2. 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.
12. Active use of opioids or marijuana for any reason at screening and unwilling or unable to discontinue use.
3.2.3. Medical Exclusion Criteria
13. Clinically significant ECG or laboratory abnormalities at the Screening Visit that would put the participant at undue risk or affect the ability of the participant to participate in the trial (in the opinion of the investigator). Screening ECG and lab results may be repeated without requiring a rescreen, as long as the participant is still within the screening window.
14. Participants whose glycemic control has been unstable within 3 months before screening (e.g. ketoacidosis requiring hospitalization).
15. Proliferative retinopathy or maculopathy requiring acute treatment.
16. Requiring dialysis.
17. Myocardial infarction or stroke in the past 6 months.
18. Known diagnosis of moderate to severe hepatic impairment (equivalent to Child-Pugh class B or C) OR aspartate aminotransferase or alanine aminotransferase ≥ 3 times the upper limit of normal during the screening process.
19. A clinically significant illness or operative procedure within 4 weeks of screening.
20. Clinically significant surgery planned during the study period. If a surgery is planned, please contact the MM for approval before randomization.
21. History of malignancy or other medical condition that would put the participant at undue risk or affect the ability of the participant to participate in the trial (in the opinion of the investigator).
22. Pregnant or nursing. 3.2.4. Psychosocial and Substance Use Disorders Exclusion Criteria
23. A clinically significant psychiatric disease that would put the participant at undue risk or affect the ability of the participant to participate in the trial (in the opinion of the investigator).
24. Alcohol use disorder or other substance use disorders (other than nicotine or caffeine) in accordance with DSM-5 criteria within 12 months of screening.
25. Positive urine drug tests defined as one or more of the following (see Urine Drug Testing Section 6.2.13.5.1):
1. Two positive urine drug tests for a prescribed opioid (buprenorphine, opiates, methadone and/or oxycodone), prior to the initiation of investigational product (IP);
2. Two positive urine drug tests for marijuana (prescribed or recreational), prior to the initiation of investigational product (IP);
3. One positive urine drug test for cocaine, ecstasy, methamphetamines, or phencyclidine (PCP);
4. One positive urine drug test for non-prescribed amphetamines, barbiturates, benzodiazepines, or opioids (buprenorphine, opiates, methadone and/or oxycodone).
26. Vulnerable persons defined as either of the following:
1. Individuals whose willingness to volunteer in a clinical study may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation or of a retaliatory response from senior members of a hierarchy in case of refusal to participate.

Pregnancy or breastfeeding
Severe psychiatric disorders
Active substance abuse
Unstable medical conditions
Inability to comply with study requirements

Contacts and Locations

Study Contact

Neha Rupeja

CONTACT

617-991-6755

nrupeja@mgh.harvard.edu

Megan Bubello

CONTACT

617-455-8729

mbubello@mgh.harvard.edu

Principal Investigator

Jessica Robinson-Papp, MD

PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Study Locations (Sites)

University of California, San Diego

San Diego, California, 92037

United States

South Lake Pain Institute

Clermont, Florida, 34711

United States

SIMEDHealth LLC

Gainesville, Florida, 32607

United States

University of Florida

Gainesville, Florida, 32611

United States

Northwestern Department of Neurology

Chicago, Illinois, 60611

United States

Healthcare Research Network (Flossmoor)

Flossmoor, Illinois, 60422

United States

University of Kansas Medical Center

Kansas City, Kansas, 66160

United States

University of Maryland - Baltimore

Baltimore, Maryland, 21201

United States

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21205

United States

MGH Department of Anesthesia, Critical Care, and Pain

Boston, Massachusetts, 02114

United States

Healthcare Research Network (Hazelwood)

Hazelwood, Missouri, 63042

United States

Columbia University Medical Center/Neurological Institute

New York, New York, 10032

United States

Mount Sinai School of Medicine

New York, New York, 10451

United States

University of Rochester

Rochester, New York, 14627

United States

Clinical Inquest Center

Beavercreek, Ohio, 45431

United States

University of Pittsburgh

Pittsburgh, Pennsylvania, 15206

United States

Low Country Pain Center

Orangeburg, South Carolina, 29118

United States

Nerve and Muscle Center of Texas

Houston, Texas, 77030

United States

University of Utah School of Medicine

Salt Lake City, Utah, 84132

United States

Eastern Virginia Medical School

Norfolk, Virginia, 23510

United States

VCU Department of Neurology

Richmond, Virginia, 23298

United States

University of Washington

Seattle, Washington, 32611

United States

University of Wisconsin

Madison, Wisconsin, 53706

United States

Collaborators and Investigators

Sponsor: James P. Rathmell, MD

Jessica Robinson-Papp, MD, PRINCIPAL_INVESTIGATOR, Icahn School of Medicine at Mount Sinai

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-09-21

Study Completion Date2025-01-01

Study Record Updates

Study Start Date2022-09-21

Study Completion Date2025-01-01

Terms related to this study

Additional Relevant MeSH Terms

Painful Diabetic Neuropathy