Low Dose Naltrexone for Pain in HIV/AIDS

Recruiting in Palo Alto (17 mi)

+2 other locations

Overseen by Anne M McKenzie-Brown, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: Emory University

Must not be taking: Opioids

Disqualifiers: Pregnancy, Bipolar, Liver disease, others

No Placebo Group

Prior Safety Data

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

The increased life expectancy of Patients Living With HIV/AIDS (PLWHA) has increased the need for therapies for chronic conditions, such as chronic pain. Pain in the HIV population is often refractory and ends up being treated with chronic opioids, which are associated with adverse effects, including hyperalgesia, constipation, and risk of overdose. Naltrexone is an opioid antagonist used in the treatment of alcohol and opioid use disorders. Low Dose Naltrexone (LDN), naltrexone at a much lower dose, is thought to be an immune modulator and has been associated with an increased CD4 count in PLWHA. Repurposing this medication is relatively inexpensive and has the potential to expand access to treatment for a painful condition experienced in PLWHA. While there are many case reports on the efficacy of LDN in symptom reduction, there are only a small number of clinical trials that specifically examine pain and symptom relief. This study will include patients who are not completely virologically controlled and will monitor the CD4 counts drawn as a part of routine care. If the CD4 count improves with LDN and with reduced symptoms, this could be a significant improvement in HIV therapy for symptom control. There have been studies showing cytokine reduction in fibromyalgia patients but they did not investigate the correlation with cytokines and pain relief. This study involves repurposing a drug used for substance use disorder to a medication with the potential to treat pain and improve symptoms for PLWHA.

Will I have to stop taking my current medications?

The trial requires that you stop using any opioids at least 10 days before starting the study. Other medications are not specifically mentioned, so it's best to discuss your current medications with the study team.

What data supports the effectiveness of the drug Low Dose Naltrexone for pain in HIV/AIDS?

Research shows that Low Dose Naltrexone (LDN) has been used to reduce chronic pain in conditions like arthritis, suggesting it might help with pain in HIV/AIDS as well. Additionally, naltrexone is known to act on opioid receptors, which are important for pain regulation. ^{1 2 3 4 5}

Is low dose naltrexone safe for humans?

Naltrexone, including its low-dose form, is generally considered safe for humans, but it can have potential liver-related side effects, especially in those with existing liver conditions. Studies have evaluated its safety in people with chronic hepatitis C and HIV, and it is used for various conditions, indicating a recognized safety profile. ^{1 2 3 6 7}

How is low-dose naltrexone different from other drugs for pain in HIV/AIDS?

Low-dose naltrexone is unique because it is a non-opioid drug that can help manage chronic pain with minimal side effects and no drug interactions, unlike traditional pain medications that often have significant adverse effects. It works by blocking opioid receptors and may reduce pain through a mechanism involving TLR-4 antagonism, making it a novel option for those with chronic pain in HIV/AIDS. ^{1 3 4 8 9}

Eligibility Criteria

This trial is for adults aged 18-65 with HIV and chronic neuropathic pain, who have a viral load under 1000 copies/ml. Participants must be fluent in English and willing to follow study rules. Excluded are those using opioids or at risk of needing them, with allergies to naltrexone, severe liver or kidney disease, certain psychiatric conditions, active substance abuse disorders, pregnant/nursing women, or not using effective contraception.

Inclusion Criteria

I have been experiencing pain greater than 4 out of 10 for more than 3 months.

Fluent English-speaking

Diagnosis of neuropathic pain using the neuropathic pain screening tool, painDETECT17

Exclusion Criteria

Prisoners

I am not breastfeeding and use effective birth control.

Allergy to naltrexone

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive low-dose naltrexone (LDN) for 12 weeks to treat neuropathic pain

12 weeks

Weekly assessments (virtual or in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

Treatment Details

Interventions

• Low Dose Naltrexone (Opioid Antagonist)

Trial Overview The trial tests Low Dose Naltrexone (LDN) as a treatment for chronic pain in patients living with HIV/AIDS. LDN is an immune modulator that may reduce pain by affecting the immune system without the adverse effects associated with opioids.

Participant Groups

Group I: Low Dose Naloxone (LDN) Experimental Treatment 1 Intervention

Once a potential subject has been identified they may be contacted with information about the study in advance of their appointment in order to allow time for them to consider the study. A qualifying pain score will be confirmed with the subject prior to initiating consent. This may occur up to 30 days before the baseline, treatment visit, but inclusion/exclusion criteria will be re-confirmed prior to initiating study treatment. Patients may also be approached during a clinic visit. Subjects will be started with 3mg LDN orally administered daily for one week with a planned increase to 4 mg/day beginning week two, if tolerated. They will be provided a 4 week supply of study medication. LDN will be given as a daytime dose.

Group II: Control Active Control 1 Intervention

Once a potential subject has been identified they may be contacted with information about the study in advance of their appointment in order to allow time for them to consider the study. A qualifying pain score will be confirmed with the subject prior to initiating consent. This may occur up to 30 days before the baseline, treatment visit, but inclusion/exclusion criteria will be re-confirmed prior to initiating study treatment. Patients may also be approached during a clinic visit. Should a patient decline participation in the treatment plan, they will be invited to participate in a control group. They will be invited to complete the PROMIS questionnaire every 4 weeks, and the NPRS pain assessment every week from Baseline through week 12. These participants will receive follow up phone calls to confirm completion of these assessments weekly and will not have any in-person visits.

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

🇺🇸 Approved in United States as Revia for:

• Alcohol use disorder
• Opioid use disorder

🇪🇺 Approved in European Union as Vivitrol for:

• Alcohol dependence
• Opioid dependence

🇨🇦 Approved in Canada as Naltrexone Hydrochloride for:

• Alcohol dependence
• Opioid dependence

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Grady Memorial Hospital Atlanta, GA

Emory University Hospital Atlanta, GA

Emory Midtown Hospital Atlanta, GA

Who Is Running the Clinical Trial?

Emory University Lead Sponsor

References

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

Pilot Study of Low-dose Naltrexone for the Treatment of Chronic Pain Due to Arthritis: A Randomized, Double-blind, Placebo-controlled, Crossover Clinical Trial. [2023] Low-dose naltrexone (LDN) is commonly used to control pain and other symptoms, especially in patients with autoimmune diseases, but with limited evidence. This study tests the efficacy of LDN in reducing chronic pain in patients with osteoarthritis (OA) and inflammatory arthritis (IA), where existing approaches often fail to adequately control pain.

2. England pubmed.ncbi.nlm.nih.gov

A sudden and unprecedented increase in low dose naltrexone (LDN) prescribing in Norway. Patient and prescriber characteristics, and dispense patterns. A drug utilization cohort study. [2022] Following a TV documentary in 2013, there was a tremendous increase in low dose naltrexone (LDN) use in a wide range of unapproved indications in Norway. We aim to describe the extent of this sudden and unprecedented increase in LDN prescribing, to characterize patients and LDN prescribers, and to estimate LDN dose sizes.

3. Netherlands pubmed.ncbi.nlm.nih.gov

Slow-release naltrexone implant versus oral naltrexone for improving treatment outcomes in people with HIV who are addicted to opioids: a double-blind, placebo-controlled, randomised trial. [2020] Untreated opioid addiction in people with HIV is associated with poor HIV treatment outcomes. Slow-release, long-acting, implantable naltrexone might improve these outcomes. Here, we present results of a study aimed to test this hypothesis.

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

Brief Report: The Association of Chronic Pain and Long-Term Opioid Therapy With HIV Treatment Outcomes. [2022] Chronic pain occurs in up to 85% of persons living with HIV and is commonly treated with long-term opioid therapy (LTOT). We investigated the impact of chronic pain and LTOT on HIV outcomes.

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

Does treating pain with alcohol affect drinking reduction among women with HIV enrolled in a clinical trial of naltrexone? [2023] Many women living with HIV (WLWH) experience pain. Alcohol use with the intent to treat pain could lead to hazardous drinking and difficulty in reducing drinking. Naltrexone acts on opioid receptors important for pain regulation and is an approved treatment for alcohol use disorder. In this secondary analysis of a randomized double-blind placebo-controlled naltrexone clinical trial, the goals were to (1) compare alcohol reduction between women who drank to treat pain and those who did not and (2) examine differences in alcohol reduction by both drinking intention and treatment arm.

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

Hepatic safety of injectable extended-release naltrexone in patients with chronic hepatitis C and HIV infection. [2019] Naltrexone (Revia, Vivitrol) is recognized as having the potential for hepatotoxicity. We evaluated the safety of intramuscular extended-release naltrexone (XR-NTX) in a cohort of patients with a high prevalence of chronic hepatitis C virus (HC V) and HIV infection undergoing treatment for opioid dependence.

7. 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] To evaluate efficacy and safety of injectable extended-release naltrexone (XR-NTX, Vivitrol), an opioid receptor antagonist, in the treatment of opioid dependence, we carried out a 1-year open-label extension study.

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

The Use of Low-Dose Naltrexone for Chronic Pain. [2019] The use of low-dose naltrexone for the treatment of chronic pain is novel because it is a nonopioid alternative. Oral naltrexone in a dosage range from 1 mg to 4.5 mg is referred to as low-dose naltrexone. Low-dose naltrexone use is "off label" and has been used successfully to manage chronic pain, autoimmune disorders, and dermatologic conditions. Low-dose naltrexone could be a viable treatment option for chronic pain because other agents for chronic pain, such as nonsteroidal agents, have adverse effects of gastrointestinal bleeding, renal injury, and increase a patient's risk of myocardial infarction or stroke. Additionally, low-dose naltrexone has minimal adverse effects, no drug-drug interactions, and is relatively inexpensive compared with other options for chronic pain.

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

Low-dose naltrexone, an opioid-receptor antagonist, is a broad-spectrum analgesic: a retrospective cohort study. [2022] Aim: To evaluate the use of low-dose naltrexone (LDN) as a broad-spectrum analgesic. Methods: Retrospective cohort study from a single pain management practice using data from 2014 to 2020. Thirty-six patients using LDN for ≥2 months were matched to 42 controls. Pain scores were assessed at initial visit and at most recent/final documented visit using a 10-point scale. Results: Cases reported significantly greater pain reduction (-37.8%) than controls (-4.3%; p < 0.001). Whole sample multivariate modeling predicts 33% pain reduction with LDN, with number needed to treat (for 50% pain reduction) of 3.2. Patients with neuropathic pain appeared to benefit even more than those with 'nociceptive'/inflammatory pain. Conclusion: LDN is effective in a variety of chronic pain states, likely mediated by TLR-4 antagonism.