Low Dose Naltrexone for Central Neuropathic Pain

Overseen By Meghann Sytsma, 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

Trial Summary

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.

What data supports the effectiveness of the drug low-dose naltrexone for central neuropathic pain?

A study found that low-dose naltrexone (LDN) significantly reduced pain scores in patients, with a 37.8% reduction compared to a 4.3% reduction in controls. This suggests that LDN can be effective in reducing chronic pain, including neuropathic pain. ^{1 2 3 4 5}

Is low-dose naltrexone safe for humans?

Low-dose naltrexone has been shown to be generally safe in humans for various conditions, including chronic pain and opioid dependence, though it may have potential liver-related side effects. Studies have evaluated its safety in different forms and doses, with no major safety concerns reported for low doses. ^{6 7 8 9 10}

How is the drug low-dose naltrexone unique for treating central neuropathic pain?

Low-dose naltrexone is unique because it is a nonopioid alternative that works at much lower doses than those used for alcohol and opioid dependency, offering pain relief with minimal side effects and no drug interactions, unlike many other pain medications. ^{10 11 12 13 14}

What is the purpose of this trial?

The goal of this pilot clinical trial is to find out how well low dose naltrexone works for people with pain due to spinal cord injury. The main questions it aims to answer are: will low dose naltrexone reduce pain, and increase the quality of life for people with central neuropathic pain due to spinal cord injury. Hypothesis 1: LDN will decrease the severity of CNP in adult patients with SCI as measured by the Neuropathic Pain Scale (NPS) Hypothesis 2: LDN will improve quality of life of patients with SCI as measured by various validated clinical tools There is no comparison group. This study is being completed to give investigators more information for how to best run a larger clinical trial. Participants will be asked to take an oral dose of 4.5mg of naltrexone, daily, for 12 weeks.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Combination treatment of neuropathic pain: Danish expert recommendations based on a Delphi process. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Pharmacologic management of neuropathic pain: evidence-based recommendations. [2022]

3. Canada pubmed.ncbi.nlm.nih.gov

PEER systematic review of randomized controlled trials: Management of chronic neuropathic pain in primary care. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Haunting of the phantom limb pain abolished by buprenorphine/naloxone. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Low-dose naltrexone, an opioid-receptor antagonist, is a broad-spectrum analgesic: a retrospective cohort study. [2022]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Review of Case Narratives from Fatal Overdoses Associated with Injectable Naltrexone for Opioid Dependence. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Hepatic safety of injectable extended-release naltrexone in patients with chronic hepatitis C and HIV infection. [2019]

8. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Injectable extended-release naltrexone for opioid dependence: an open label study of long-term safety and efficacy]. [2016]

9. England pubmed.ncbi.nlm.nih.gov

Serious adverse events reported in placebo randomised controlled trials of oral naltrexone: a systematic review and meta-analysis. [2023]

10. Australia 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. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

The Use of Low-Dose Naltrexone for Chronic Pain. [2019]

12. United States pubmed.ncbi.nlm.nih.gov

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

13. United States pubmed.ncbi.nlm.nih.gov

Is low-dose naltrexone effective in chronic pain management? [2023]

14. United States pubmed.ncbi.nlm.nih.gov

Low-Dose Naltrexone for Chronic Pain: Update and Systemic Review. [2021]