Modality Choice Before and After Failure for the Treatment of Painful Diabetic Neuropathy

• Cognitive Behavioral Therapy (CBT) (Device): 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).
• Oral Medication (Drug): 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
• Topical Medication (Drug): 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)

Primary outcomes

• Patient-centered utility function as a measure for efficacy and tolerability [Up to 8 months.]: 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).

Secondary outcomes

• Pain intensity [Up to 8 months.]: Pain intensity as measured by first question of the "Pain, Enjoyment, General Activity" (PEG) numeric rating scale, where a score of 0 is no pain and 10 is the worst pain imaginable.
• Pain interference [Up to 8 months.]: Pain interference as measured by the sum of the second two questions of the "Pain, Enjoyment, General Activity" (PEG) numeric rating scale, where a score of 0 is no interference with daily life and 20 is the complete interference with daily life.
• Discontinuation [Up to 8 months]: Rate of treatment discontinuation for any reason, including withdrawal From enrollment to end of treatment at 8 months.
• Related adverse events [Up to 8 months.]: Adverse events reported by local sites and determined to be related to the treatment.
• Physical functioning/Quality of Life (QOL) [Up to 8 months.]: Physical function/QOL as measured by the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical functioning Short Form 6b, a 5 question questionnaire. Each question is measured with a likert scale, where 5 is "without any difficulty" and 1 is "unable to do"
• Neuropathy specific QOL [Up to 8 months]: Neuropathy Quality of Life (NeuroQOL) evaluates symptoms and function in regard to quality of life over the past four weeks. Range 1-15, higher score indicates neuropathy having a greater impact on quality of life.
• Depression [Up to 8 months]: As measured by the Patient Health Questionnaire (PHQ-2), a two-question questionnaire where each depression symptom is scored on a scale of 0-3, where 0 is "not at all" and 3 is "nearly every day". The total score range is 0-6 where the higher score indicates more depression symptoms.
• Anxiety [Up to 8 months]: As measured by the General Anxiety Disorder (GAD-2), a two-question questionnaire where each anxiety symptom is scored on a scale of 0-3, where 0 is "not at all" and 3 is "nearly every day". The total score range is 0-6 where the higher score indicates more anxiety symptoms.
• Sleep [Up to 8 months]: Sleep Quality represented by the sum of scores on the PROMIS Sleep Disturbance 6a and an additional question regarding sleep duration.
• Pain Catastrophizing [Up to 8 months]: As measured by the Pain Catastrophizing Scale Short Form 6, where a score of 0 is catastrophizing "not at all" and 52 is catastrophizing "all the time"
• Global treatment satisfaction [Up to 8 months]: As measured by Patient Global Impression of Change (PGIC), a single question on a scale of 0-6, where 0 is "very much improved" and 6 is "very much worse".
• Substance use screener [Up to 8 months]: As measured by the Tobacco, Alcohol, Prescription Medications, and other Substance (TAPS 1) questionnaire, which is five questions on a scale of 0-4, where 0 is "daily or almost daily use" and 4 is "never use".

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Diabetes
* Painful Diabetic Neuropathy (confirmed at screening visit)
* Willing to accept random treatment assignment to any of the proposed interventions

Exclusion Criteria:

* 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

• Brian Callaghan, MD, Principal investigator, University of Michigan