Modality Choice Before and After Failure for the Treatment of Painful Diabetic Neuropathy
MCPAIN
2 other identifiers
interventional
600
1 country
23
Brief Summary
The research team will perform a comparative-effectiveness sequential, multiple assignment, randomized trial in painful diabetic neuropathy (PDN) patients for 8 total months, divided into two 4-month stages. 600 participants 18+ with PDN will be enrolled in this study. The main goal is to compare the utility of three modalities (oral, topical, and behavioral) for initial PDN treatment, and to compare the utility of switching modalities versus continuing with the same modality for non-responders. Pain and discontinuation will be assessed weekly, whereas other outcomes will be assessed monthly for 8 months.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4
Started Oct 2026
Longer than P75 for phase_4
23 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 25, 2026
CompletedFirst Posted
Study publicly available on registry
August 31, 2026
CompletedStudy Start
First participant enrolled
October 1, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2031
ExpectedStudy Completion
Last participant's last visit for all outcomes
October 1, 2031
September 28, 2026
September 1, 2026
4.6 years
August 25, 2026
September 25, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Patient-centered utility function as a measure for efficacy and tolerability
Efficacy and tolerability will be assessed and measured as utility function. Utility function ranges from 0-1.75, 0 being the lowest utility function and 1.75 being the highest utility function. Utility function that is a composite of efficacy (0-1) and discontinuation (0-1).
Up to 8 months.
Secondary Outcomes (12)
Pain intensity
Up to 8 months.
Pain interference
Up to 8 months.
Discontinuation
Up to 8 months
Related adverse events
Up to 8 months.
Physical functioning/Quality of Life (QOL)
Up to 8 months.
- +7 more secondary outcomes
Study Arms (12)
Oral Medication then New Oral Medication
EXPERIMENTALParticipants randomized to oral medications, and are considered non-responders at 4 months will be rerandomized to a new treatment modality (oral, topical, behavioral). Those re-randomized to oral medications will select a new oral medication for the next 4 months.
Oral Medication then Same Oral Medication
EXPERIMENTALParticipants randomized to oral medications, and are considered responders at 4 months will continue with the same oral medication for the next 4 months.
Oral Medication then Topical Medication
EXPERIMENTALParticipants randomized to oral medications, and are considered non-responders at 4 months will be rerandomized to a new treatment modality (oral, topical, behavioral). Those re-randomized to topical medications will select a topical medication for the next 4 months.
Oral Medication then Cognitive Behavioral Therapy
EXPERIMENTALParticipants randomized to oral medications, and are considered non-responders at 4 months will be re-randomized to a new treatment modality (oral, topical, behavioral). Those re-randomized to a behavioral intervention will begin self-guided CBT for the next 4 months.
Topical Medication then New Topical Medication
EXPERIMENTALParticipants randomized to topical medications, and are considered non-responders at 4 months will be rerandomized to a new treatment modality (oral, topical, behavioral). Those re-randomized to topical medications will select a new topical medication for the next 4 months.
Topical Medication then Same Topical Medication
EXPERIMENTALParticipants randomized to topical medications, and are considered responders at 4 months will continue with the same topical medication for the next 4 months.
Topical Medication then Oral Medication
EXPERIMENTALParticipants randomized to topical medications, and are considered non-responders at 4 months will be re-randomized to a new treatment modality (oral, topical, behavioral). Those re-randomized to oral medications will select an oral medication for the next 4 months.
Topical Medication then Cognitive Behavioral Therapy
EXPERIMENTALParticipants randomized to topical medications, and are considered non-responders at 4 months will be re-randomized to a new treatment modality (oral, topical, behavioral). Those re-randomized to a behavioral intervention will begin self-guided CBT for the next 4 months.
Cognitive Behavioral Therapy then Same Cognitive Behavioral Therapy
EXPERIMENTALParticipants randomized to behavioral interventions will all begin with self-guided CBT. If considered responders at 4 months they will continue with self-guided CBT for the next 4 months.
Cognitive Behavioral Therapy then New Cognitive Behavioral Therapy
EXPERIMENTALParticipants randomized to behavioral interventions will all begin with self-guided CBT. If considered non-responders at 4 months, they will be rerandomized to a new treatment modality (oral, topical, behavioral). Those re-randomized to a behavioral intervention will begin traditional CBT for the next 4 months.
Cognitive Behavioral Therapy then Oral Medication
EXPERIMENTALParticipants randomized to behavioral interventions will all begin with self-guided CBT. Non-responders at 4 months will be re-randomized to a new treatment modality (oral, topical, behavioral). Those re-randomized to oral medications will select an oral medication for the next 4 months.
Cognitive Behavioral Therapy then Topical Medication
EXPERIMENTALParticipants randomized to behavioral interventions will all begin with self-guided CBT. Non-responders at 4 months will be re-randomized to a new treatment modality (oral, topical, behavioral). Those re-randomized to topical medications will select a topical medication for the next 4 months.
Interventions
Participants will work with study team to begin web-based, self-guided CBT (non-significant risk device) or traditional (one on one) CBT with a therapist (behavioral, not a device).
Participants will work with their physician to select an oral medication from a list commonly used to treat PDN. Patients will follow standard of care dosing and tapering of the assigned drug. Serotonin-Norepinephrine Reuptake Inhibitors (SNRI's): Duloxetine, Venlafaxine, Desvenlafaxine Tricyclic Antidepressants (TCAs): Amitriptyline, Nortriptyline Gabapentinoids: Gabapentin, Pregabalin Sodium Channel Blockers: Oxcarbazepine, Lamotrigine, Lacosamide
Participants will work with their physician to select a topical medication from a list commonly used to treat PDN. 0.075% capsaicin cream (4 times daily) 4-5% lidocaine patches (1-4 patches every 24 hours)
Eligibility Criteria
You may qualify if:
- Diabetes
- Painful Diabetic Neuropathy (confirmed at screening visit)
- Willing to accept random treatment assignment to any of the proposed interventions
You may not qualify if:
- Pregnancy or plans to become pregnant during the study
- History of neuropathy from causes other than diabetes as determined through medical and family history, physical and neurologic examinations
- HbA1c \>10%
- Participation in an experimental medication trial within 3 months of starting the study
- Undergoing therapy for malignant disease other than basal-cell or squamous-cell skin cancer
- Medical or psychiatric reason for not being a study candidate according to the site PI's discretion
- Contraindications preventing trialing two interventions within any of the 3 modalities
- Cirrhosis of the liver
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (23)
Stanford University
Stanford, California, 94305, United States
University of Florida-Jacksonville
Jacksonville, Florida, 32209, United States
Rush University Medical Center
Chicago, Illinois, 60612, United States
University of Iowa
Iowa City, Iowa, 52242, United States
Tulane University
New Orleans, Louisiana, 70118, United States
Johns Hopskins University
Baltimore, Maryland, 21224, United States
University of Michigan
Ann Arbor, Michigan, 48104, United States
Allina Health-Neurosciences Research
Minneapolis, Minnesota, 55407, United States
University of Minnesota
Minneapolis, Minnesota, 55455, United States
Mayo Clinic Rochester
Rochester, Minnesota, 55902, United States
University of Missouri
Columbia, Missouri, 65201, United States
University of Nebraska
Omaha, Nebraska, 68198, United States
Columbia University
New York, New York, 10027, United States
Will Cornell Medicine
New York, New York, 10065, United States
University of North Carolina
Chapel Hill, North Carolina, 27599, United States
Duke University
Durham, North Carolina, 27708, United States
Oregon Health & Science University
Portland, Oregon, 97239, United States
University of Pittsburgh
Titusville, Pennsylvania, 16354, United States
Meharry Medical College
Nashville, Tennessee, 37208, United States
University of Vanderbilt
Nashville, Tennessee, 37235, United States
DHR Health Institute for Research and Development
Edinburg, Texas, 78539, United States
BaylorScott & White University Medical Center
McKinney, Texas, 75071, United States
Essentia Health
Spooner, Wisconsin, 54801, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Brian Callaghan, MD
University of Michigan
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- CROSSOVER
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Professor of Neurology
Study Record Dates
First Submitted
August 25, 2026
First Posted
August 31, 2026
Study Start
October 1, 2026
Primary Completion (Estimated)
May 1, 2031
Study Completion (Estimated)
October 1, 2031
Last Updated
September 28, 2026
Record last verified: 2026-09
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, ICF, CSR
- Time Frame
- At the time of publication of the research project's primary results in a peer-reviewed journal - for at least 7 years
- Access Criteria
- A data requestor that submits a data request will be evaluated for its overall qualifications and experience (e.g., across a proposed team of specified individuals) to achieve the stated research purpose underlying the data request. Neither PCORI nor the Awardee investigators will provide technical assistance directly to data requestors. However, either party may provide input to the repository upon request.
Full, de-identified datasets will be deposited in a PCORI-designated repository at study completion. Study team will follow all rules and regulations of the funding agency, which can be found here: https://www.pcori.org/about/governance/pcoris-policy-data-management-and-data-sharing