Low Dose Naltrexone for Pain in HIV/AIDS

Recruiting at 2 trial locations

Overseen By Anne M McKenzie-Brown, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Emory University

Must not be taking: Opioids

Disqualifiers: Pregnancy, Bipolar, Liver disease, 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: 3

Duration: 12 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests Low Dose Naltrexone (LDN) to determine its effectiveness in reducing pain for people living with HIV/AIDS. Chronic pain is common in this group, and current treatments often rely on opioids, which have many side effects. Although typically used for substance use disorders, LDN might also boost the immune system and alleviate pain. Individuals with HIV who have experienced ongoing pain for more than three months and maintain a viral load under a certain level may qualify for this study. The trial aims to find a safer, more effective method to manage chronic pain in people with HIV/AIDS. As a Phase 4 trial, it involves an FDA-approved treatment and seeks to understand how it can benefit more patients.

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 is the safety track record for Low Dose Naltrexone?

Research shows that Low Dose Naltrexone (LDN) is generally safe. Earlier studies reported mild side effects in some participants, such as fatigue, sleep disturbances, or stomach issues like diarrhea or nausea. These side effects were usually not serious.

LDN is a smaller dose of naltrexone, a medication typically used to help people with alcohol or opioid addictions stay off these substances. At lower doses, LDN may support the immune system. For those considering joining a clinical trial, it's important to know that LDN is not yet officially approved for any condition. However, research has explored its potential to help with chronic pain and to strengthen the immune system in people with HIV/AIDS. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard treatments for pain in HIV/AIDS, which often include opioids or non-steroidal anti-inflammatory drugs (NSAIDs), Low Dose Naltrexone (LDN) offers a unique approach. LDN is exciting because it works by modulating the immune system and reducing inflammation, which may help manage pain with fewer side effects compared to traditional painkillers. Additionally, LDN is taken in small oral doses, potentially improving patient adherence and minimizing the risk of dependency associated with higher-dose opioids. Researchers are enthusiastic about LDN's potential to provide effective pain relief with a lower risk of addiction and side effects.

What evidence suggests that Low Dose Naltrexone might be an effective treatment for pain in HIV/AIDS?

Research has shown that low-dose naltrexone (LDN) can reduce pain in conditions such as fibromyalgia, Crohn's disease, and multiple sclerosis. Studies have found that LDN effectively manages pain, with some patients experiencing significant relief. In this trial, participants will receive LDN to evaluate its effectiveness in managing chronic pain in patients with HIV/AIDS. Additionally, LDN has been linked to higher CD4 counts in people with HIV/AIDS, potentially improving their overall health. This suggests that LDN could be a promising option for these patients. The treatment is generally well-tolerated and might offer a safer alternative to traditional pain medications like opioids. ^{1 6 7 8 9}

Who Is on the Research Team?

Anne M McKenzie-Brown, MD

Principal Investigator

Emory University

Are You a Good Fit for This Trial?

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

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

Interventions

• Low Dose Naltrexone

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.

How Is the Trial Designed?

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. Participants will start 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 with a four-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

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

Published Research Related to This Trial

In a 48-week study involving 200 participants with opioid addiction and HIV, the naltrexone implant group showed a significant improvement in maintaining viral loads below 400 copies per mL at 48 weeks compared to the oral naltrexone group, suggesting that long-acting naltrexone may enhance HIV treatment outcomes.

Despite some serious adverse events, including deaths in both groups, the study indicates that longer opioid blockade from the implant may help protect against missed antiretroviral therapy doses and impulsive behaviors that could lead to relapse.

NCBI (Pubmed)

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. Krupitsky, E., Blokhina, E., Zvartau, E., et al.[2020]

Following a 2013 TV documentary, the use of low dose naltrexone (LDN) in Norway surged, with 15,297 patients (0.3% of the population) receiving prescriptions, indicating a significant increase in off-label use despite limited evidence.

The median daily dose of LDN was 3.7 mg, and a notable 20% of doctors, including 71% of general practitioners, prescribed LDN at least once, reflecting a high willingness to adopt this treatment.

NCBI (Pubmed)

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. Raknes, G., Småbrekke, L.[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]

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]

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 study of 2334 individuals living with HIV, chronic pain was found to significantly increase the risk of suboptimal retention in care and virologic failure, particularly in those not receiving long-term opioid therapy (LTOT).

Interestingly, among those with chronic pain, LTOT was associated with lower rates of virologic failure, suggesting that LTOT may have a protective effect on HIV outcomes that warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brief Report: The Association of Chronic Pain and Long-Term Opioid Therapy With HIV Treatment Outcomes. Merlin, JS., Long, D., Becker, WC., et al.[2022]

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]

In a study of 194 women living with HIV, those who used alcohol to manage pain reduced their drinking more slowly than those who did not, indicating that pain management strategies may influence alcohol consumption patterns.

Naltrexone treatment was effective in reducing alcohol consumption overall, but the most significant reductions were observed in women not using alcohol for pain relief, suggesting that addressing pain in treatment guidelines could improve outcomes for those with hazardous drinking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does treating pain with alcohol affect drinking reduction among women with HIV enrolled in a clinical trial of naltrexone? Parisi, CE., Gracy, HR., Bush, NJ., et al.[2023]

In a pilot study involving 23 patients with osteoarthritis and inflammatory arthritis, low-dose naltrexone (LDN) did not show a significant difference in reducing pain interference compared to a placebo, suggesting it may not be effective for nociceptive pain associated with arthritis.

The study also found no significant changes in pain severity, fatigue, depression, or quality of life, indicating that LDN may not provide the expected benefits for patients with these conditions.

NCBI (Pubmed)

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. Beaudette-Zlatanova, B., Lew, RA., Otis, JD., et al.[2023]

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Low Dose Naltrexone for Pain in Patients With HIV

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In this study, 40 adult patients with HIV will take low-dose naltrexone for 12 weeks to treat neuropathic pain. We will measure pain scores and markers of ...

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