Relistor Injection for Chronic Pain in HIV

Recruiting at 1 trial location

Overseen By Saurabh Aggarwal, MD., PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Florida International University

Must be taking: Antiretroviral therapy

Must not be taking: Methadone, Buprenorphine

Disqualifiers: Anemia, Blood disorders, Infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 2 visits

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether certain cells in the body are linked to increased pain sensitivity in people with HIV. Researchers are testing the effectiveness of Relistor injections on chronic pain in individuals with and without HIV. The trial includes several groups: those with HIV experiencing chronic widespread pain, those with HIV without such pain, and similar groups for those without HIV. Potential participants may qualify if they live with HIV and receive stable treatment at the UAB 1917 Clinic, or if they do not have HIV but experience body pain more than once a week for over three months. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could lead to new insights and treatments for chronic pain.

Will I have to stop taking my current medications?

The trial does not require participants to stop taking their current medications for pain management, as long as they have been stable on them for at least 60 days. However, medications like methadone or buprenorphine used for opioid addiction treatment may be exceptions.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Relistor, an injectable treatment, is generally safe. One study found that long-term use did not reveal any new safety concerns. It effectively treats constipation caused by opioid use, the condition for which the FDA has approved it.

Some individuals might experience stomach pain, so monitoring for severe or worsening pain is important. Overall, Relistor's safety is supported by its current use in medical practice, suggesting it could be a safe choice for those considering joining this trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Relistor for chronic pain in HIV patients because it offers a novel way to tackle pain management. Unlike traditional opioids, which can lead to significant side effects and dependency issues, Relistor works by blocking opioid receptors in the gut, thereby reducing constipation without affecting pain relief. This unique mechanism allows it to potentially improve the quality of life for those who suffer from chronic pain without the typical downsides of opioid treatments. Plus, its injectable form can offer more precise dosing, tailored to the patient's weight, which might enhance its effectiveness.

What evidence suggests that this trial's treatments could be effective for chronic pain in HIV?

Research has shown that Relistor, also known as methylnaltrexone, can quickly ease certain types of pain and symptoms in people with long-term health issues. Studies indicate it can start working fast, with relief lasting for a few months. It is especially used to manage pain related to opioid use without reducing the pain relief that opioids provide. In this trial, participants will receive either saline or Relistor randomly to assess its effectiveness in managing chronic widespread pain in both HIV-positive and HIV-negative individuals. While it helps with pain management, some people might experience side effects like stomach pain. Overall, evidence suggests that Relistor effectively manages specific pain symptoms, offering hope for those with chronic pain conditions. ^{5 6 7 8 9}

Who Is on the Research Team?

Saurabh Aggarwal, MD., PhD

Principal Investigator

Florida International University

Are You a Good Fit for This Trial?

This trial is for adults aged 19-65 with HIV and chronic widespread pain, receiving stable antiretroviral therapy at the UAB 1917 Clinic. HIV-negative individuals can join if they have chronic pain or no significant pain. Exclusions include anemia, blood disorders, uncontrolled diabetes, neurological diseases, severe psychiatric issues, active infections, certain medications (excluding stable pain management drugs), recent major surgery, cognitive impairment that affects understanding of the study procedures, pregnancy, systemic rheumatic disease, cachexia or severe frailty.

Inclusion Criteria

I am HIV negative and either experience pain more than once a week for 3 months or have little to no pain.

I am living with HIV and am on a stable ART regimen.

I am between 19 and 65 years old.

Exclusion Criteria

You have a serious mental illness that needed hospital treatment or have been thinking about hurting yourself.

I do not have high blood pressure or heart/blood vessel diseases.

Any participant deemed to be actively suicidal upon study screening will be escorted to the UAB emergency room and evaluated by the Psychiatry Service

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Quantitative sensory testing (QST) and blood samples are collected to measure endogenous opioid peptides

1 day

1 visit (in-person)

Treatment

Participants are randomly administered saline or RELISTOR and undergo quantitative sensory testing

2 visits

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Relistor Injectable Product

Trial Overview The trial tests Relistor Injectable Product to see if it helps reduce hypersensitivity in people with HIV by affecting opioid peptides released by immune cells. It aims to understand novel mechanisms behind chronic widespread pain in these patients.

How Is the Trial Designed?

Group I: HIV positive without chronic widespread pain Experimental Treatment 1 Intervention

50 Participants will be randomly administered saline or RELISTOR (Individuals weighing 38-\<62 kg will receive an 8 mg dose; those weighing 62-114 kg will receive a 12 mg dose; Participants weighing more than 114 kg will receive 0.15 mg/kg) in counterbalance between visit 1 and visit 2.

Group II: HIV positive with chronic widespread pain Experimental Treatment 1 Intervention

50 Participants will be randomly administered saline or RELISTOR (Individuals weighing 38-\<62 kg will receive an 8 mg dose; those weighing 62-114 kg will receive a 12 mg dose; Participants weighing more than 114 kg will receive 0.15 mg/kg) in counterbalance between visit 1 and visit 2.

Group III: HIV negative without chronic widespread pain Experimental Treatment 1 Intervention

50 Participants will be randomly administered saline or RELISTOR (Individuals weighing 38-\<62 kg will receive an 8 mg dose; those weighing 62-114 kg will receive a 12 mg dose; Participants weighing more than 114 kg will receive 0.15 mg/kg) in counterbalance between visit 1 and visit 2.

Group IV: HIV negative with chronic widespread pain Experimental Treatment 1 Intervention

50 Participants will be randomly administered saline or RELISTOR (Individuals weighing 38-\<62 kg will receive an 8 mg dose; those weighing 62-114 kg will receive a 12 mg dose; Participants weighing more than 114 kg will receive 0.15 mg/kg) in counterbalance between visit 1 and visit 2.

Relistor Injectable Product is already approved in United States, Canada for the following indications:

Approved in United States as Relistor for:

• Opioid-induced constipation (OIC) in adults with chronic non-cancer pain
• OIC in adults with advanced illness or pain caused by active cancer

Approved in Canada as Relistor for:

• Opioid-induced constipation (OIC) in adults with chronic non-cancer pain
• OIC in adults with advanced illness or pain caused by active cancer

Who Is Running the Clinical Trial?

Florida International University

Lead Sponsor

Trials

114

Recruited

19,400+

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Published Research Related to This Trial

In a study involving 40 advanced AIDS patients, both transdermal buprenorphine and fentanyl significantly reduced various types of neuropathic pain and improved overall patient performance, indicating their effectiveness as pain management options.

Both opioids were well tolerated and did not negatively impact immune function, with buprenorphine showing a tendency to stabilize CD4+ levels, making it a safer choice for patients with compromised immune systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of transdermal buprenorphine and transdermal fentanyl in the treatment of neuropathic pain in AIDS patients. Canneti, A., Luzi, M., Di Marco, P., et al.[2022]

In a survey of 148 ambulatory HIV patients, 82 reported experiencing pain, with 60-70% indicating that it significantly interfered with their daily lives.

Despite the high prevalence of pain, 40% of those suffering were not receiving any treatment, and those who were treated only achieved a mean pain relief of 65%, highlighting the need for better pain management strategies in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inadequate treatment of pain in ambulatory HIV patients. McCormack, JP., Li, R., Zarowny, D., et al.[2019]

A survey of 3,255 patients indicated that transdermal buprenorphine is effective for managing chronic pain, with 81% of respondents reporting good or very good pain relief, especially beneficial for those with stable cancer and non-cancer pain.

Adverse effects were generally mild and similar to other opioids, with only 4% experiencing local erythema and 1% pruritus, suggesting that the buprenorphine patch may be a safer alternative for patients who have had side effects from oral pain medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buprenorphine TDS: use in daily practice, benefits for patients. Radbruch, L.[2022]

In a 12-week pilot study involving 16 HIV-positive, opioid-dependent patients, integrating buprenorphine/naloxone into HIV care showed high treatment retention, with 81% completing the study and significant reductions in opioid use, as evidenced by urine tests.

Patients also experienced improvements in HIV-related health markers, with a significant decline in HIV-1 RNA levels, indicating that buprenorphine treatment is not only feasible but also beneficial for managing both opioid dependence and HIV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A trial of integrated buprenorphine/naloxone and HIV clinical care. Sullivan, LE., Barry, D., Moore, BA., et al.[2013]

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 phase III study involving 344 patients with osteoarthritis pain, morphine/naltrexone significantly improved pain management compared to placebo, demonstrating its efficacy in treating moderate to severe chronic pain.

In a 12-month safety study with 465 participants, morphine/naltrexone was well tolerated and provided effective pain relief, with significant improvements in pain scores observed from the first week of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Morphine/naltrexone. Duggan, ST., Scott, LJ.[2021]

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]

Buprenorphine, especially in its transdermal patch form, is effective for managing chronic pain, including neuropathic pain, and has demonstrated both efficacy and safety in randomized trials and post-marketing studies.

The transdermal delivery system allows for continuous and stable drug levels, making it a suitable option for chronic pain management compared to on-demand administration, and buprenorphine's unique receptor activity as a partial agonist may contribute to its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Transdermal buprenorphine: a current overview of pharmacological and clinical data]. Faymonville, ME., Libbrecht, D.[2015]

Citations

1. withpower.com withpower.com/trial/phase-chronic-pain-8-2021-f667c

Relistor Injection for Chronic Pain in HIV In a 48-week study involving 200 participants with opioid addiction and HIV, the naltrexone implant group showed a significant improvement in maintaining viral ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2899781/

Methylnaltrexone: the evidence for its use in the management ... Onset of the effect is rapid and improvement is maintained for at least 3 months during the drug treatment. The action of methylnaltrexone is dose dependent.

3. ema.europa.eu ema.europa.eu/en/documents/product-information/relistor-epar-product-information_en.pdf

Relistor, INN-methylnaltrexone bromide - EMA Patients should be monitored for severe, persistent, or worsening abdominal pain; methylnaltrexone bromide should be discontinued if this symptom occurs ...

4. has-sante.fr has-sante.fr/jcms/c_986782/en/relistor-ct-5881-english-version

relistor The most common adverse effects observed in these studies (> 10 %) were: abdominal pain. (17.5% and 32% of patients, depending on the study), ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0885392408000936

Subcutaneous Methylnaltrexone for the Treatment of ... Methylnaltrexone relieved opioid-induced constipation at doses ≥5 mg in patients with advanced illness, and did not reduce analgesia or cause opioid withdrawal ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5914419/

Long-Term Safety and Efficacy of Subcutaneous ... Long-term subcutaneous methylnaltrexone was well tolerated, with no new safety concerns, and provided consistent opioid-induced constipation relief.

7. ir.bauschhealth.com ir.bauschhealth.com/news-releases/2021/12-22-2021-120114539

Relistor® (Methylnaltrexone Bromide) Data is Published in ... The study results demonstrated that an initial dose of RELISTOR injection effectively produced rescue-free laxation (RFL) in greater proportions of severely ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2016/208271Orig1s000OtherR.pdf

208271Orig1s000 - accessdata.fda.gov For methylnaltrexone bromide oral tablet, Relistor® NDA 208271 seeks FDA approval for the indication, opioid-induced constipation in adults with ...

9. relistorhcp.com relistorhcp.com/treating-oic

Treating OIC | RELISTOR® (methylnaltrexone bromide) 80% of people in a survey of 322 patients taking oral opioid therapy daily and over-the-counter (OTC) laxatives reported still being constipated.