Low Dose Naltrexone for Complex Regional Pain Syndrome

(LDN-CRPS Trial)

Overseen By Alexandra Sideris, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Hospital for Special Surgery, New York

Must not be taking: Opioids, Alcohol

Disqualifiers: Disc herniation, Infection, Malignancy, Pregnancy, others

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

Compensation: Varies

Number of Visits: 3

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether low-dose naltrexone can help manage pain in individuals with Complex Regional Pain Syndrome (CRPS), a condition causing severe, ongoing pain and swelling. Participants will take either the medication or a placebo (a sugar pill resembling the real medication) daily for six months, with four visits to the trial site. The trial aims to determine if naltrexone can reduce pain and symptoms and to monitor any side effects. Individuals who have experienced CRPS symptoms for more than three months and suffer from severe pain affecting daily life might be suitable for this study. As a Phase 4 trial, this research focuses on understanding how this already FDA-approved and effective treatment can benefit more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently using opioid drugs or alcohol.

What is the safety track record for low dose naltrexone?

Research has shown that low-dose naltrexone is generally safe for use. Studies have found that this treatment can significantly relieve pain, especially for individuals with long-term pain conditions like Complex Regional Pain Syndrome (CRPS). In past research, low-dose naltrexone reduced pain and improved daily activities.

Most reported side effects have been mild. Some individuals experienced trouble sleeping, vivid dreams, or mild stomach issues, but these were uncommon. Notably, the FDA has already approved naltrexone for other uses, which supports its safety.

Overall, current evidence suggests that low-dose naltrexone is safe for most people, with usually manageable side effects. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Low dose naltrexone is unique because it leverages the body's endorphin system to potentially reduce pain and inflammation in Complex Regional Pain Syndrome (CRPS). Unlike standard treatments like physical therapy, nerve blocks, or medications like corticosteroids and opioids, low dose naltrexone acts as an opioid receptor antagonist in a low dose, which may help in modulating the immune response and pain without the risks associated with high-dose opioids. Researchers are excited because this approach could offer a novel, less risky way to manage CRPS symptoms, providing relief with fewer side effects.

What evidence suggests that low dose naltrexone might be an effective treatment for Complex Regional Pain Syndrome?

Research has shown that low dose naltrexone (LDN) might alleviate symptoms of Complex Regional Pain Syndrome (CRPS). In some studies, patients reported significant pain reduction and improved mobility after starting LDN. Others found that LDN eased ongoing pain and enhanced sleep quality. Some cases even showed symptoms nearly disappearing. Overall, these findings suggest that LDN could be a promising option for people with CRPS. In this trial, participants will receive either LDN or placebo sugar capsules, alongside standard care for CRPS. ^{1 4 6 7 8}

Who Is on the Research Team?

Alexandra Sideris, PhD

Principal Investigator

Hospital for Special Surgery, New York

Semih Gungor, M.D.

Principal Investigator

Hospital for Special Surgery, New York

Are You a Good Fit for This Trial?

This trial is for individuals with Complex Regional Pain Syndrome (CRPS), a rare chronic pain condition. Participants should be willing to take medication daily and attend three in-person follow-up visits over six months. Specific inclusion and exclusion criteria details are not provided.

Inclusion Criteria

I have CRPS with severe pain that disrupts my daily activities.

Meeting CRPS diagnostic criteria using the Budapest Clinical Diagnostic Criteria

I have had CRPS pain and symptoms for over 3 months.

Exclusion Criteria

Uncontrolled medical and psychiatric condition

I currently have an infection.

Current or planned pregnancy within the study period

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive low dose naltrexone or placebo capsules daily for 6 months, with titration of dosage over the first 3 months

6 months

3 visits (in-person) at 1, 3, and 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Low dose naltrexone

Trial Overview The study is testing the effectiveness of low dose naltrexone, an opiate blocker, compared to placebo sugar capsules in managing CRPS pain. Patients will be randomly assigned to either treatment without knowing which one they receive.

How Is the Trial Designed?

Group I: Low dose naltrexone Experimental Treatment 1 Intervention

Half of all enrolled patients will be randomized to receive capsules with the active low dose naltrexone (LDN) ingredient. LDN will be titrated over time to minimize potential side effects, with the initial dose starting at 1.5mg and eventually increasing up to 4.5mg. Neither the patient nor treating physician will be aware of the group in which the patient was randomized into until after study conclusion. All patients will be requested to take the respective daily dose and follow the titration schedule as instructed. All patients enrolled in the study, regardless of their randomization, will have standard of care treatment for CRPS according to their symptoms and the clinical judgment of the treating clinician.

Group II: Placebo sugar capsules Placebo Group 1 Intervention

Half of all enrolled patients will be randomized to receive placebo sugar capsules. Neither the patient nor treating physician will be aware of the group in which the patient was randomized into until after study conclusion. All patients will be requested to take the respective daily dose and follow the titration schedule as instructed. All patients enrolled in the study, regardless of their randomization, will have standard of care treatment for CRPS according to their symptoms and the clinical judgment of the treating clinician.

Who Is Running the Clinical Trial?

Hospital for Special Surgery, New York

Lead Sponsor

Trials

257

Recruited

61,800+

Published Research Related to This Trial

Transdermal buprenorphine was effective in reducing pain intensity by approximately 50% in two patients with refractory complex regional pain syndrome (CRPS).

The treatment was generally safe, with manageable side effects such as application site rash, which was treated with a topical steroid spray.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Use of Transdermal Buprenorphine in Complex Regional Pain Syndrome: A Report of Two Cases. Onofrio, S., Vartan, CM., Nazario, M., et al.[2018]

Two patients with Complex Regional Pain Syndrome (CRPS) experienced significant symptom relief, including dystonic spasms and fixed dystonia, after being treated with low-dose naltrexone (LDN) alongside other therapies.

LDN works by antagonizing the Toll-like Receptor 4 pathway and reducing activated microglia, suggesting it may be an effective option for patients who do not respond to conventional CRPS treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Complex Regional Pain Syndrome (CRPS) using low dose naltrexone (LDN). Chopra, P., Cooper, MS.[2021]

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]

In a study of 50 patients with complex regional pain syndrome type I (CRPS-I), prednisolone 20 mg was found to be as effective as 40 mg in reducing pain, with all patients achieving over 50% reduction in pain scores after one month.

The lower dose of prednisolone (20 mg) was safer for diabetic patients, requiring fewer adjustments to their antidiabetic medications compared to the higher dose (40 mg).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prednisolone 20 mg vs 40 mg in complex regional pain syndrome type I: A randomized controlled trial. Kalita, J., Pandey, PC., Shukla, R., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06306157

Low Dose Naltrexone Therapy for Complex Regional Pain ... This study aims to collect preliminary data on pain scores, symptom severity, and side-effects in patients with Complex Regional Pain Syndrome randomized to ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3661907/

Treatment of Complex Regional Pain Syndrome (CRPS ... We describe positive outcomes of two CRPS patients, after they were treated with low-dose naltrexone (a glial attenuator), in combination with other CRPS ...

3. painphysicianjournal.com painphysicianjournal.com/current/pdf?article=NzI1OQ%3D%3D&journal=136

Low-Dose Naltrexone Use for Patients with Chronic ... We found that low-dose naltrexone treatment was positively associated with symptom relief in patients experiencing chronic pain, dystonia, and sleep ...

4. painri.com painri.com/post/management-of-complex-regional-pain-syndrome-crps-with-ldn-low-dose-naltrexone

Management of Complex Regional Pain Syndrome (CRPS ... Within six weeks of initiating LDN, the patient reported a marked reduction in pain intensity, improved mobility, and diminished sensory ...

5. cureus.com cureus.com/articles/350289-therapeutic-uses-and-efficacy-of-low-dose-naltrexone-a-scoping-review

Therapeutic Uses and Efficacy of Low-Dose Naltrexone Treatment efficacy ranged from mild symptom or pain relief to complete symptom clearance or disease remission. For example, Bolton et al.

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

Low-Dose Naltrexone (LDN) for Chronic Pain at a Single ... Patients who experienced greater than 50% pain relief from LDN were more likely to have the diagnosis of neuropathic pain or complex regional ...

7. researchgate.net researchgate.net/profile/Daniel-Berland/publication/377894571_Efficacy_and_Safety_of_Low_Dose_Naltrexone_for_Chronic_Pain/links/66844366f3b61c4e2ca90795/Efficacy-and-Safety-of-Low-Dose-Naltrexone-for-Chronic-Pain.pdf

Efficacy and Safety of Low Dose Naltrexone for Chronic Pain The primary outcome was change in the Pain, Enjoyment of Life, and General Activity (PEG) score after. LDN. Thirty-one patients were included.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02502162

NCT02502162 | Low-Dose Naltrexone for the Treatment of ... The investigators are testing treatment with low-dose naltrexone (LDN) for symptom relief of complex regional pain syndrome (CRPS). Study participants will be ...