Clinical trial NCT05537935: Low Dose Naltrexone for Pain in Patients With HIV
Official title: Low Dose Naltrexone (LDN) for the Treatment of Chronic Neuropathic Pain in Patients With Human Immunodeficiency Virus (HIV), a Prospective, Pragmatic, Open Label Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Human Immunodeficiency Virus
Chronic Neuropathic Pain
Keywords: Low dose Naltrexone
Naltrexone
Pain
Lead sponsor: Emory University
Sponsor class: OTHER
First posted: 2022-09-13
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 \<60 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

Primary outcomes:
measure: Changes in Numerical Pain Score
timeFrame: Study weeks 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10,11 and 12
Secondary outcomes:
measure: Changes in PROMIS pain Score
timeFrame: Study weeks 0, week 4, week 8 and week 12
measure: Changes in Average pain Score
timeFrame: Study weeks 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10,11 and 12
measure: Changes in IL-1 levels
timeFrame: Study week 0 and week 12
measure: Changes in IL-18 levels
timeFrame: Study week 0 and week 12
measure: Changes in Met-Enkephalin Levels
timeFrame: Study week 0 and week 12
measure: Changes in endorphin levels
timeFrame: Study week 0 and week 12
measure: Changes in CD4 counts
timeFrame: Study week 0 and week 12
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Grady Memorial Hospital
state: Georgia
city: Atlanta
country: United States
facility: Emory Midtown Hospital
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
Study officials:
affiliation: Emory University
name: Anne M McKenzie-Brown, MD
role: PRINCIPAL_INVESTIGATOR
References: