Low Dose Naltrexone for Pain in Patients With HIV

NCT05537935 | Recruiting Phase 4 DMC FDA Drug

• 2 other identifiers: STUDY000044222025P011310
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 3

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.

Conditions

Chronic Neuropathic Pain; Human Immunodeficiency Virus

Keywords

Low dose Naltrexone; Naltrexone; Pain

Outcome Measures

Primary Outcomes (1)

• Changes in Numerical Pain Score

  The study team will give participants a link to the online PROMIS questionnaire that includes a numerical pain rating scale (NPRS) to complete using an iPad or computer and will verbally ask questions to establish baseline information required for the study. If they have no computer access, they will be given a hard copy of the PROMIS questionnaire and NPRS to complete for future visits. The Numerical Pain Rating Scale (NPRS) is a subjective measure in which individuals rate their pain on an eleven-point numerical scale. The scale is composed of 0 (no pain at all) to 10 (worst imaginable pain). Changes in pain scores, measured on the numerical pain score (NPS) on the Pain Intensity section of the PROMIS-29 Profile v2.0. This will be measured weekly during the 12-week study period.

  Study weeks 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10,11 and 12

Secondary Outcomes (7)

• Changes in PROMIS pain Score

  Study weeks 0, week 4, week 8 and week 12

• Changes in Average pain Score

  Study weeks 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10,11 and 12

• Changes in IL-1 levels

  Study week 0 and week 12

• Changes in IL-18 levels

  Study week 0 and week 12

• Changes in Met-Enkephalin Levels

  Study week 0 and week 12

Study Arms (2)

Control

NO 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 Naloxone (LDN)

EXPERIMENTAL

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.

Drug: Low Dose Naltrexone

Interventions

Low Dose Naltrexone 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.

Also known as: Questionnaires

Low Dose Naloxone (LDN)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-75, male and female
• 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

You may not qualify if:

• 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:
• Use of oral, injected, or implanted hormonal methods of contraception or;
• Placement of an intrauterine device (IUD) or intrauterine system (IUS);
• Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical /vault caps) with spermicidal foam/gel/film/cream/vaginal suppository;
• Total abstinence;
• 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

Sponsors & Collaborators

• Emory University: lead

Study Sites (3)

Grady Memorial Hospital

Atlanta, Georgia, 30303, United States

RECRUITING

Emory Midtown Hospital

Atlanta, Georgia, 30308, United States

RECRUITING

Emory University Hospital

Atlanta, Georgia, 30322, United States

RECRUITING

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; Pain

Interventions

Naltrexone; Surveys and Questionnaires

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Naloxone; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Data Collection; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Officials

• Anne M McKenzie-Brown, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anne M McKenzie-Brown, MD

CONTACT

404-686-2410; amckenz@emory.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: September 9, 2022
• First Posted: September 13, 2022
• Study Start: April 28, 2023
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: April 9, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: Beginning 3 months and ending 5 years following article publication
• Access Criteria: Data will be shared with researchers who provide a methodologically sound proposal, to achieve aims of the approved proposal. ? Proposals may be directed to amckenz@emory.edu. To gain access, data requestors will need to sign a data access agreement. Data are available 5 years at a 3rd party website

Locations

US (3)