Low-Dose Naltrexone for the Treatment of Painful Diabetic Neuropathy

NCT04678895 | Recruiting Phase 2 FDA Drug

• 1 other identifier: D20145
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

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

Keywords

Low-Dose Naltrexone; Painful Diabetic Neuropathy

Outcome Measures

Primary Outcomes (2)

• Change in Pain Disability Index

  Pain Disability index (PDI) Score measures the degree to which pain interferes with activities. Every item ranges from 0 (no interference) to 10 (total interference). The total PDI score can range from 0 to 70, a higher score indicating more interference with functioning across a range of activities.

  Enrollment through week 12

• Change in Numeric Rating Scale for Pain

  Percent Change in Numerical Rating Scale (NRS) Scores Between Baseline to End of Placebo Treatment and Between Baseline to End of LDN Treatment. NRS is scored between 1-10 with 1 being no pain and 10 being the worst pain one can experience.

  Enrollment through week 12

Secondary Outcomes (4)

• Ratio of Pain Catastrophizing Scores Compared to Change in Pain Disability Index

  Questionnaire will be administered on enrollment and compared to final pain score data, approximately 12 weeks.

• Ratio of Pain Catastrophizing Scores Compared to Change in Numeric Rating Scale

  Questionnaire will be administered on enrollment and compared to final pain score data, approximately 12 weeks.

• Ratio of Pre-treatment Expectations Score Compared to Change in Pain Disability Index

  Questionnaire will be administered on enrollment and compared to final pain score data, approximately 12 weeks.

• Ratio of Pre-treatment Expectations Compared to Change in Numeric Rating Scale

  Questionnaire will be administered on enrollment and compared to final pain score data, approximately 12 weeks.

Study Arms (2)

Group A, Low-Dose Naltrexone, Then Placebo

EXPERIMENTAL

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).

Drug: Naltrexone; Drug: Placebo

Group B, Placebo, Then Low-Dose Naltrexone

EXPERIMENTAL

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.

Drug: Naltrexone; Drug: Placebo

Interventions

Naltrexone DRUG

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.

Also known as: LDN

Group A, Low-Dose Naltrexone, Then Placebo; Group B, Placebo, Then Low-Dose Naltrexone

Placebo DRUG

Naltrexone matched placebo capsule.

Group A, Low-Dose Naltrexone, Then Placebo; Group B, Placebo, Then Low-Dose Naltrexone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Dartmouth-Hitchcock Medical Center: lead

Study Sites (1)

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03766, United States

RECRUITING

MeSH Terms

Conditions

Diabetic Neuropathies

Interventions

Naltrexone

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Naloxone; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Bruce M Vrooman, MD

  Dartmouth-Hitchcock Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bruce Vrooman

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Investigational Pharmacy will perform the randomization process and remain unblinded throughout the study.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Section Chief, Center for Pain and Spine

Model Details: Randomized, double-blind, placebo-controlled, crossover trial.

Study Record Dates

• First Submitted: December 7, 2020
• First Posted: December 22, 2020
• Study Start: December 22, 2020
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: May 6, 2026

Record last verified: 2026-05

Locations

US (1)