Recruiting
Phase 2

Naltrexone

Sponsor:

Dartmouth-Hitchcock Medical Center

Code:

NCT04678895

Conditions

Painful Diabetic Neuropathy

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Naltrexone

Placebo

Study Details

Brief summary:

Diabetes affects more than 30 million people in the United States and is a leading cause of morbidity. Over 25% diabetics also suffer from debilitating painful diabetic neuropathy in the lower legs and feet. This pain can be severe, difficult to control, and have a significant negative impact on quality of life. Opioid medications have historically been a mainstay of treatment for this pain, despite the risks. As the death toll from the U.S. opioid epidemic continues to rise, the need for quality alternative non-opioid medications to treat pain becomes more urgent. One of these potential medications is Low-Dose Naltrexone (LDN). This drug is reported to work by enhancing the body's natural pain relieving mechanisms and decreases inflammation by targeting specific cells called microglia which have been shown to influence chronic pain. LDN has been shown to be a safe medication with minimal side effects. Its efficacy has been demonstrated in other painful conditions but has never been fully studied for treating painful diabetic neuropathy. The goal of this randomized, placebo-controlled trial is to determine if LDN is effective for treating the pain caused by diabetic neuropathy. LDN's mechanism of action is well suited to treating painful diabetic neuropathy, and LDN shows significant promise as a safe, non-opioid alternative that can decrease pain and improve quality of life for those suffering from this painful condition.

Conditions

Painful Diabetic Neuropathy

Study ID

NCT04678895

Start date

Dec 22, 2020

Status verified date

May, 2026

Completion date

Dec, 2026

Anticipated

Primary completion date

Dec, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

35 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Group A, Low-Dose Naltrexone, Then Placebo

Group A will receive active drug (Naltrexone 1 capsule by mouth daily, 1.5mg x1 week, 3mg x1 week, and 4.5 mg x6 weeks) for the first 8 weeks. Capsules of different dosages will be indistinguishable. Then followed by 4 weeks of placebo (placebo capsule will be matched with LDN capsule, microcrystalline cellulose filler, 1 capsule daily).

experimental: Group B, Placebo, Then Low-Dose Naltrexone

Group B will receive 4 weeks of placebo (placebo capsule will be matched with LDN capsule, microcrystalline cellulose filler, 1 capsule daily). Then followed by active drug (Naltrexone 1 capsule by mouth daily, 1.5mg x1 week, 3mg x1 week, and 4.5 mg x6 weeks) for the last 8 weeks. Capsules of different dosages will be indistinguishable.

Interventions

Naltrexone

Capsule with doses of 1.5mg, 3mg, and 4.5 mg to allow for drug titration. Capsules of different dosages will be indistinguishable to allow for maintenance of blinding.

Placebo

Naltrexone matched placebo capsule.

Primary outcome measure

  • Change in Pain Disability Index [ Time Frame: Enrollment through week 12 ]
  • Change in Numeric Rating Scale for Pain [ Time Frame: Enrollment through week 12 ]

Central Contacts and Locations

Central contacts

Bruce Vrooman

603-650-5000bruce.m.vrooman@hitchcock.org

Locations

Dartmouth-Hitchcock Medical Center

Recruiting

Lebanon, New Hampshire, United States, 03766

Contacts

Bruce M Vrooman, MD

603-650-2225bruce.m.vrooman@hitchcock.org

More Information

Sponsor

Dartmouth-Hitchcock Medical Center

Last update posted

May 6, 2026

Last verified

May, 2026

Keywords

  • Low-Dose Naltrexone
  • Painful Diabetic Neuropathy

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Dartmouth-Hitchcock Medical Center on 2026-05-06.