Low Dose Naltrexone for Central Neuropathic Pain

Overseen By Sarah Golus, BS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Medical College of Wisconsin

Must not be taking: Opioids, Naltrexone

Disqualifiers: Severe depression, Brain injury, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of a low dose of naltrexone in reducing pain and improving the quality of life for individuals with pain from a spinal cord injury. Participants will take a daily dose of 4.5mg of naltrexone for 12 weeks. The trial targets those who have had a spinal cord injury for more than six months and experience central neuropathic pain related to that injury. The researchers aim to gather early data to help plan a larger study in the future. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important early findings.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot have adjusted your pain medications in the past month or be on chronic opioid treatment. You also cannot be currently taking naltrexone or other similar drugs.

Is there any evidence suggesting that low dose naltrexone is likely to be safe for humans?

Research has shown that low-dose naltrexone (LDN) is generally safe for treating certain types of pain, such as nerve pain. Studies have found that LDN does not cause any serious side effects. For instance, a study on its use for fibromyalgia found no major negative effects in participants taking LDN.

LDN works on the nervous system to ease pain and is considered a safer option compared to other non-opioid pain medications. While more research is needed, current evidence supports LDN's safety for managing pain. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for central neuropathic pain?

Low Dose Naltrexone is unique because it offers a different approach to treating central neuropathic pain compared to standard options like anticonvulsants and antidepressants. Unlike these treatments, which often target nerve signals or neurotransmitter levels, Low Dose Naltrexone works by modulating the immune system and reducing inflammation, which may contribute to pain relief. Researchers are excited about this treatment because it uses a much lower dose than typically prescribed for other conditions, potentially minimizing side effects while effectively managing pain.

What evidence suggests that low dose naltrexone might be an effective treatment for central neuropathic pain?

Research has shown that low dose naltrexone (LDN), which participants in this trial will receive, can help reduce various types of nerve pain. Studies have found that LDN lowers inflammation and pain by targeting specific areas in the body. In one study, patients using LDN experienced a 49% drop in their pain levels. Additionally, those taking LDN reported a better quality of life, including improved physical abilities and less severe pain. This suggests that LDN could be a promising treatment for nerve pain in individuals with spinal cord injuries. ^{1 5 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults with spinal cord injury who experience central neuropathic pain. Participants should be willing to take a daily oral dose of medication and commit to the study for 12 weeks.

Inclusion Criteria

English speaking

I have nerve pain due to spinal cord injury, confirmed by a specialist.

I have a spinal cord injury in my neck or upper back.

Exclusion Criteria

Chronic opioid treatment

Allergy to naltrexone

I have a planned surgery during the study period.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants take a daily oral dose of 4.5mg of naltrexone for 12 weeks

12 weeks

Regular virtual visits for check-ins and questionnaires

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Naltrexone

Trial Overview

The trial tests if a low dose (4.5mg) of naltrexone taken daily can reduce pain severity and improve quality of life in individuals with neuropathic pain due to spinal cord injury, using specific scales and clinical tools.

How Is the Trial Designed?

Group I: Low Dose Naltrexone Experimental Treatment 1 Intervention

Daily dose of 4.5mg of naltrexone

Naltrexone is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Vivitrol for:

• Alcohol dependence
• Opioid use disorder

Approved in European Union as Naltrexone for:

• Opioid dependence
• Alcohol dependence

Approved in Canada as Vivitrol for:

• Opioid use disorder
• Alcohol dependence

Who Is Running the Clinical Trial?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

Published Research Related to This Trial

Low-dose naltrexone, at doses one-tenth of those used for treating alcohol and opioid dependency, has shown potential in alleviating pain, as demonstrated in a case study.

Although there are no randomized clinical trials yet, the case study indicates that low-dose naltrexone can significantly improve pain symptoms that have not responded to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-Dose Naltrexone: A New Therapy Option for Complex Regional Pain Syndrome Type I Patients. Sturn, KM., Collin, M.[2017]

In a 1-year open-label extension study involving 114 patients, injectable extended-release naltrexone (XR-NTX) demonstrated long-term efficacy, with 50.9% of participants remaining abstinent from opioids throughout the study.

The treatment was generally safe, with only 21.1% of patients reporting adverse events and no severe adverse events noted, although 16.7% experienced elevated liver function tests.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Injectable extended-release naltrexone for opioid dependence: an open label study of long-term safety and efficacy]. Krupitsky, EM., Nunes, EV., Ling, W., et al.[2016]

Low-dose naltrexone is as effective as amitriptyline for treating painful diabetic neuropathy, while also having a better safety profile, based on a single randomized controlled trial.

In patients with fibromyalgia, doses as low as 5.4 mg of low-dose naltrexone reduced pain in 95% of cases, indicating its strong efficacy in managing pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is low-dose naltrexone effective in chronic pain management? Radi, R., Huang, H., Rivera, J., et al.[2023]

Low-dose naltrexone, ranging from 1 mg to 4.5 mg, is a promising nonopioid alternative for managing chronic pain, autoimmune disorders, and dermatologic conditions, despite being used off-label.

It offers a safer profile compared to traditional pain medications, as it has minimal adverse effects, no significant drug-drug interactions, and is more cost-effective, reducing risks associated with other pain management options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Use of Low-Dose Naltrexone for Chronic Pain. Bostick, KM., McCarter, AG., Nykamp, D.[2019]

In a study involving 67 participants with painful diabetic neuropathy, low-dose naltrexone (2 mg) showed similar efficacy to amitriptyline (10 mg) in reducing pain over 6 weeks, indicating it could be a viable alternative treatment.

Naltrexone had a significantly better safety profile, with only 8 adverse events reported compared to 52 for amitriptyline, suggesting it may be a safer option for patients suffering from this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of low-dose naltrexone in painful diabetic neuropathy: A randomized, double-blind, active-control, crossover clinical trial. Srinivasan, A., Dutta, P., Bansal, D., et al.[2022]

A review of 263 cases related to Vivitrol (extended-release naltrexone) found that 84.6% of fatal overdoses occurred within two months after the last injection, highlighting a critical period for overdose risk.

The study suggests that there may be a link between Vivitrol discontinuation and increased overdose risk, indicating the need for further investigation and monitoring during this time frame.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of Case Narratives from Fatal Overdoses Associated with Injectable Naltrexone for Opioid Dependence. Saucier, R., Wolfe, D., Dasgupta, N.[2019]

A study involving 250 opioid-dependent patients, many of whom had chronic hepatitis C virus (HCV) and HIV, found that intramuscular extended-release naltrexone (XR-NTX) did not significantly increase liver enzyme levels compared to a placebo, indicating its safety in this population.

Even though some patients experienced elevated liver enzymes, these levels improved over time, and no specific symptoms were linked to these elevations, suggesting that XR-NTX can be safely administered to patients with mild to moderate chronic HCV and/or HIV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatic safety of injectable extended-release naltrexone in patients with chronic hepatitis C and HIV infection. Mitchell, MC., Memisoglu, A., Silverman, BL.[2019]

A case study of a patient suffering from 2 years of phantom limb pain (PLP) showed significant improvement with sublingual buprenorphine/naloxone, highlighting its effectiveness in treating this challenging condition.

Buprenorphine/naloxone works through multiple mechanisms, including acting as a long-acting mu-opioid agonist and antagonizing other opioid receptors, suggesting it could be a promising early treatment option for PLP compared to traditional opioid therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Haunting of the phantom limb pain abolished by buprenorphine/naloxone. Srejic, U., Banimahd, F.[2023]

In a study of 36 patients using low-dose naltrexone (LDN) for at least 2 months, significant pain reduction was observed, with a 37.8% decrease in pain scores compared to only 4.3% in the control group, indicating LDN's efficacy as an analgesic.

LDN appears particularly beneficial for patients with neuropathic pain, and the study suggests that its pain-relieving effects may be mediated through TLR-4 antagonism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose naltrexone, an opioid-receptor antagonist, is a broad-spectrum analgesic: a retrospective cohort study. Martin, SJ., McAnally, HB., Okediji, P., et al.[2022]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10276990/

Low-Dose Naltrexone (LDN) for Chronic Pain at a Single ...

Conclusion. Patients with all types of neuropathic pain, including CRPS, were significantly more likely to have pain relief from LDN than ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06306157

Low Dose Naltrexone Therapy for Complex Regional Pain ...

In much lower doses (1.5 - 4.5mg per day), naltrexone has been seen to reduce inflammation and nerve pain by instead blocking a different set of receptors ...

3.

academic.oup.com

academic.oup.com/painmedicine/article/24/11/1270/7193901

Low-dose naltrexone's utility for non-cancer centralized pain ...

Overall, the body of evidence revealed improvement in patient-reported pain severity and in outcomes related to hyperalgesia, physical function, quality of life ...

4.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S1542012420301890

Low-dose naltrexone is effective and well-tolerated for ...

LDN resulted in a 49.22% decrease in mean pain score from 6.13 ± 1.93 to 3.23 ± 2.60 (p < 0.001). Mean QoL scores by the OPAS were 5.84 ± 2.57 at the first ...

5.

neurology.org

neurology.org/doi/10.1212/WNL.0000000000206418

Use of Low Dose Naltrexone in a Cohort of Patients with ...

To explore the efficacy of low dose naltrexone (LDN) in a group of patients with biopsy-confirmed cryptogenic small fiber neuropathy (SFN).

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06723561?term=low%20dose%20naltrexone&aggFilters=status:not%20rec%20enr%20act&viewType=Table&rank=10

Treating Central Neuropathic Pain With Low Dose ...

This study is being completed to provide the first evidence that low dose naltrexone may be able to lower pain and improve quality of life for people with pain ...

7.

asra.com

asra.com/news-publications/asra-newsletter/newsletter-item/asra-news/2023/11/06/low-dose-naltrexone-is-it-really-worth-the-hype

Low Dose Naltrexone: Is it Really Worth the Hype?

This review will discuss the pharmacology and current evidence for use of Low Dose Naltrexone (LDN) for treating chronic pain. Pharmacology: ...

8.

journals.lww.com

journals.lww.com/annals-of-medicine-and-surgery/fulltext/2025/05000/efficacy_and_safety_of_low_dose_naltrexone__ldn_.47.aspx

Efficacy and safety of low-dose naltrexone (LDN) in...

LDN is considered to be effective in the treatment of fibromyalgia. No serious adverse effects were reported in treatment group.