Using Low-Dose Naltrexone to Treat Painful Diabetic Neuropathy

Low-Dose Naltrexone for the Treatment of Painful Diabetic Neuropathy, a Small, Randomized, Double-blind, Placebo-controlled Crossover Trial

PHASE2 · Dartmouth-Hitchcock Medical Center · NCT04678895

This study is testing if low-dose naltrexone can help people with painful diabetic neuropathy feel less pain after other treatments haven't worked.

Quick facts

PhasePHASE2
Study typeInterventional
Enrollment35 (estimated)
Ages18 Years and up
SexAll
SponsorDartmouth-Hitchcock Medical Center (other)
Locations1 site (Lebanon, New Hampshire)
Trial IDNCT04678895 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of low-dose naltrexone in treating painful diabetic neuropathy, a common complication of diabetes that causes severe pain in the lower legs and feet. The study employs a randomized, double-blind, placebo-controlled, crossover design, where participants will receive both the investigational drug and a placebo in alternating phases. Participants must have a diagnosis of painful diabetic neuropathy for over six months and have failed at least one standard treatment. The goal is to assess whether low-dose naltrexone can provide relief from pain while minimizing the risks associated with opioid medications.

Who should consider this trial

Good fit: Ideal candidates are adults over 18 with a diagnosis of painful diabetic neuropathy for more than six months who have not responded to standard treatments.

Not a fit: Patients currently using opioids or those with other known causes of neuropathic pain may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer a safer, non-opioid alternative for managing pain in diabetic neuropathy patients.

How similar studies have performed: While low-dose naltrexone has shown promise in treating other painful conditions, its use for diabetic neuropathy is novel and has not been extensively tested.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

1. Diagnosis of Painful Diabetic Neuropathy (PDN) for \>6 months
2. Has failed at least one prior standard treatment for PDN (Gabapentin, duloxetine, etc)
3. No other known causes of lower extremity neuropathic pain
4. Subjects capable of giving informed consent
5. Greater than 18 years of age
6. Stable on all current non-opioid pain medication for at least 1 month
7. English as primary language

Exclusion Criteria:

1. Known allergy to naltrexone or naloxone
2. Presence of known causes of lower extremity neuropathic pain not attributed to PDN
3. Active substance use disorder or alcohol use disorder as defined by DSM-V (The Diagnostic and Statistical Manual of Mental Disorders)
4. Current treatment for substance use disorder or alcohol use disorder
5. Current opioid therapy or on opioid therapy within the past 1 month

Where this trial is running

Lebanon, New Hampshire

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Painful Diabetic Neuropathy, Low-Dose Naltrexone

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.