What side effects are associated with this type of intervention?

Common treatments for diabetic neuropathy, such as anticonvulsants (gabapentin, pregabalin), antidepressants (duloxetine, amitriptyline), and topical agents (capsaicin, lidocaine), have various side effects. Gabapentin and pregabalin can cause dizziness, drowsiness, and peripheral edema. Duloxetine and amitriptyline may lead to dry mouth, constipation, and increased risk of cardiovascular issues. Topical agents like capsaicin can cause local skin irritation and burning sensations, while lidocaine patches may result in localized skin reactions. These side effects should be considered when choosing a treatment plan.

What prior FDA approvals exist?

The FDA has approved several medications for the treatment of diabetic neuropathy, primarily focusing on pain relief and inflammation reduction. These include anticonvulsants like pregabalin (Lyrica) and gabapentin (Neurontin), which modulate pain by affecting neurotransmitter release. Additionally, serotonin-norepinephrine reuptake inhibitors (SNRIs) such as duloxetine (Cymbalta) are approved for their dual action on pain relief and mood improvement. While Low-Dose Naltrexone (LDN) is being studied for its potential to enhance natural pain relief and decrease inflammation by targeting microglia, it has not yet been approved by the FDA for diabetic neuropathy.

What other types of research exist?

Promising alternatives to Low-Dose Naltrexone for diabetic neuropathy include: 1) AMD3100, which alleviates neuropathic pain by augmenting leukocyte-derived endogenous opioid secretion; 2) Capsaicin 8% dermal patch, which has shown efficacy in reducing peripheral neuropathic pain; and 3) Gabapentin, which is commonly used for neuropathic pain management. These alternatives target different mechanisms of pain relief and inflammation reduction.

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Opioid Antagonist

Low-Dose Naltrexone for Diabetic Neuropathy

Phase 2

Recruiting

Led By Bruce M Vrooman, MD

Research Sponsored by Dartmouth-Hitchcock Medical Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Diagnosis of Painful Diabetic Neuropathy (PDN) for >6 months

Greater than 18 years of age

Must not have

Presence of known causes of lower extremity neuropathic pain not attributed to PDN

Current opioid therapy or on opioid therapy within the past 1 month

Timeline

Screening 3 weeks

Treatment Varies

Follow Up enrollment through week 12

Summary

This trial is testing Low-Dose Naltrexone (LDN) to see if it can help people with diabetes who have painful neuropathy in their legs and feet. LDN aims to reduce pain by enhancing the body's natural pain relief and decreasing inflammation. The study hopes to find a safer, non-opioid alternative for managing this difficult-to-treat pain.

Who is the study for?

Adults over 18 with painful diabetic neuropathy for more than 6 months, who've tried and failed at least one standard treatment like Gabapentin or duloxetine. Participants must be stable on current non-opioid pain meds for a month, speak English, and can't have other causes of lower leg pain or any substance use disorders.

What is being tested?

The trial is testing Low-Dose Naltrexone (LDN) against a placebo to see if it helps with the pain from diabetic neuropathy without using opioids. LDN works by boosting natural pain relief in the body and reducing inflammation.

What are the potential side effects?

Low-Dose Naltrexone is generally safe with minimal side effects reported. However, some may experience mild issues such as nausea, headache, sleep disturbances or vivid dreams.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have been diagnosed with painful diabetic neuropathy for over 6 months.

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I am older than 18 years.

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My leg pain is not caused by any known condition.

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I have tried at least one standard treatment for nerve pain without success.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I have nerve pain in my legs not caused by diabetic nerve damage.

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I am currently using opioids or have used them in the last month.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ enrollment through week 12

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~enrollment through week 12

This trial's timeline: 3 weeks for screening, Varies for treatment, and enrollment through week 12 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Pain

Change in Pain Disability Index

Secondary study objectives

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

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

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

+1 more

Side effects data

From 2011 Phase 4 trial • 165 Patients • NCT00006489

24%

Nausea

12%

Headache

12%

Cold

10%

Dry Mouth

10%

Fatigue

Gastrointestinal Issues

Muscle Aches

Vomiting

Serious Suicidal Ideation

Stomach Virus

Diarrhea

Constipation

Changes to Vision

Loose Stool

Increased Irritability

Sedation

Stomach Pain

Increased Bowel Movements

Toothache

100%

80%

60%

40%

20%

Study treatment Arm

Naltrexone + Supportive Counseling

Naltrexone + CBT (Prolonged Exposure Therapy)

Placebo + CBT (Prolonged Exposure Therapy)

Placebo + Supportive Counseling

Trial Design

2Treatment groups

Experimental Treatment

Group I: Group B, Placebo, Then Low-Dose NaltrexoneExperimental Treatment2 Interventions

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.

Group II: Group A, Low-Dose Naltrexone, Then PlaceboExperimental Treatment2 Interventions

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).

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Naltrexone

2005

Completed Phase 4

~2420

Placebo

1995

Completed Phase 3

~2670

0 / 6Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for diabetic neuropathy include gabapentinoids (e.g., gabapentin, pregabalin), which modulate calcium channels to reduce nerve excitability, and antidepressants (e.g., amitriptyline, duloxetine), which inhibit the reuptake of serotonin and norepinephrine to enhance pain inhibition pathways. Low-Dose Naltrexone (LDN) works by enhancing the body's natural pain relief mechanisms and reducing inflammation through microglia modulation. These mechanisms are crucial for diabetic neuropathy patients as they address both the pain and the underlying inflammatory processes, potentially improving pain management and quality of life.