Low Dose Naltrexone for Pain in Patients With HIV

NCT ID: NCT05537935

Last Updated: 2025-07-17

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-04-28
• Study Completion Date: 2026-12-31

Brief Summary

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.

Detailed Description

More than one million people in the United States live with HIV. In 2018, Black/African Americans made up 42% of the new HIV diagnoses, while Hispanic persons accounted for 27%. Black/African Americans and Hispanics with an HIV diagnosis receive less care for treatment and maintenance of HIV than their Caucasian counterparts and are thus less likely to have adequate suppression of the virus. Many people living with HIV/AIDS have untreated chronic pain, which negatively affects their quality of life. Neuropathic (nerve) pain, including painful HIV neuropathy, is notoriously difficult to treat. Opioids (narcotics) are often used to treat chronic pain in patients, with inconsistent results. We now know that opioids for chronic pain are more consistently known for a multitude of side effects than effective long-term pain relief. Lesser-known side effects of chronic opioids include suppressing, or dampening, the immune system, making opioids particularly undesirable as a chronic therapy for pain in the HIV patient population. Other therapies for neuropathic pain have undesirable side effects. Naltrexone is FDA-approved for addiction and is not used to treat a medical disease. Low-dose naltrexone (LDN) is an off-label use of naltrexone with some evidence that it may help chronic pain, such as fibromyalgia and some types of neuropathic (nerve) pain. LDN is a much lower dose of naltrexone. It has to be compounded to 1/10 of the usual dose to be repurposed to treat pain. 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 inflammation while they are taking LDN. Naltrexone repurposed as LDN has the potential to greatly enhance the quality of life of HIV patients. This is particularly meaningful given the healthcare disparities often associated with HIV.

Conditions

Human Immunodeficiency Virus; Chronic Neuropathic Pain

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Control

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Low Dose Naloxone (LDN)

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 Type: EXPERIMENTAL

Low Dose Naltrexone

Intervention Type: DRUG

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 4-week supply of study medication. The most common side effects are difficulty sleeping and vivid dreams, which are seen more frequently with nighttime dosing, so LDN will be given as a daytime dose.

Interventions

Low Dose Naltrexone

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 4-week supply of study medication. The most common side effects are difficulty sleeping and vivid dreams, which are seen more frequently with nighttime dosing, so LDN will be given as a daytime dose.

Intervention Type: DRUG

Other Intervention Names

Questionnaires

Eligibility Criteria

Inclusion Criteria

• Age 18-75, male and female
• HIV infection with a viral load of < 1000 copies/ml for the past six months. (That is the viral load below which, according to the 2018 American College of Obstetricians and Gynecologists (ACOG) Committee Opinion, there is not thought to be a significant risk of HIV transmission from the mother to the fetus with vaginal delivery. This was thought to be a reasonable cut-off for inclusion in this study.)
• Diagnosis of neuropathic pain (pain that is associated with a lesion or disease involving the somatosensory nervous system, e.g. painful neuropathy, radicular pain, complex regional pain syndrome, nerve-related pain following spine surgery, etc.) using the neuropathic pain screening tool, painDETECT17, as part of the neuropathic pain screen.
• Pain score > 4/10 on average on the NPRS lasting > 3 months (chronic pain)
• Capable of informed consent and willing to comply with the study requirements
• Fluent English-speaking

Exclusion Criteria

• Allergy to naltrexone (not applicable to the control group)
• Current use of any opioids, up to 10 days before the start of the study (not applicable to the control group)
• Pregnant women
• Nursing mothers and women of childbearing potential not using contraception known to be highly effective (not applicable for the control group). Highly effective contraception methods include a combination of any two of the following during the 12-week study period:

1. Use of oral, injected, or implanted hormonal methods of contraception or;

2. Placement of an intrauterine device (IUD) or intrauterine system (IUS);

3. Barrier methods of contraception; condom or occlusive cap (diaphragm or cervical /vault caps) with spermicidal foam/gel/film/cream/vaginal suppository;

4. Total abstinence;

5. Male/female sterilization.

• Bipolar disorder, schizophrenia, poorly controlled anxiety or depression
• Diagnosis of liver disease, e.g. cirrhosis
• Current diagnosis of either chronic kidney disease or acute kidney injury and/or a GFR <45 at baseline
• Acute viral hepatitis A, B, C
• Patients who self-report as having tested positive for COVID-19 or have been diagnosed with another viral illness within the past ten days.
• Patients with a known or suspected diagnosis of long-term COVID
• Active drug or alcohol use disorder
• People who may require opioid therapy during the duration of the study, e.g. upcoming surgery
• Transportation issues interfering with return study visits (NA for the control group)
• Adults unable to consent
• Prisoners

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Anne Marie McKenzie-Brown

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Anne M McKenzie-Brown, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Grady Memorial Hospital

Atlanta, Georgia, United States

Site Status: RECRUITING

Emory Midtown Hospital

Atlanta, Georgia, United States

Site Status: RECRUITING

Emory University Hospital

Atlanta, Georgia, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Anne M McKenzie-Brown, MD

Role: CONTACT

amckenz@emory.edu

404-686-2410

Facility Contacts

Brian Bobzien, MD

Role: primary

brian.patrick.bobzien@emory.edu

404-616-5078

Kimberly A Workowski, MD

Role: primary

kworkow@emory.edu

404-686-7893

Anne M McKenzie-Brown, MD

Role: primary

amckenz@emory.edu

404-686-2410

Other Identifiers

STUDY00004422

Identifier Type: -

Identifier Source: org_study_id