Low Dose Naltrexone (LDN) for Management of Fatigue in Prostate Cancer Patients on Androgen Deprivation Therapy (ADT)

Phase II Clinical Trial Evaluating the Safety and Efficacy of Low Dose Naltrexone (LDN) for the Management of Fatigue in Prostate Cancer Patients on Androgen Deprivation Therapy (ADT)

The study is being done to see if a small daily dose of naltrexone (LDN, 3 mg pill) can help reduce tiredness (fatigue) in men with prostate cancer. All men in this study are being treated with hormone therapy (also called androgen deprivation therapy, or ADT). Some may also be taking newer hormone medicines such as apalutamide, daralutamide, enzalutamide, or abiraterone.

Study Overview

• Status: Not yet recruiting
• Conditions: Metastatic Prostate Cancer
• Intervention / Treatment: Drug: Naltrexone

Detailed Description

The purpose of this study is to learn if low dose naltrexone can safely improve energy and reduce fatigue in men receiving these treatments.

Primary Objectives

1. Characterize mitochondrial bioenergetics, inflammation and oxidative stress after ADT and the remediating effects of LDN.
2. Assess the impact of low-dose naltrexone (LDN) on Cancer-related fatigue as measured by the FACIT-F questionnaire.

Secondary Objectives

1. Evaluate quality of life (QOL) measures [Functional Assessment of Cancer Therapy-Prostate (FACT-P) on subjects receiving LDN.
2. Evaluate safety and tolerability of LDN.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Aaron Holley; Phone Number: 5016868274; Email: JAHolley@uams.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• Histologically or cytologically confirmed biochemical recurrence and on ADT for at least 3 months. Metastatic castrate-sensitive and castrate-resistant prostate cancer on ADT with or without novel hormonal therapy like apalutamide, darolutamide, enzalutamide and abiraterone.
• Initiation of hormonal ablative therapy within 3 months of registration.
• ECOG performance status <3.

• Patients must have normal organ and marrow function as defined below:

  • leukocytes >3,000/μL
  • absolute neutrophil count >1,500/μL
  • platelets >100,000/μL
  • total bilirubin within normal institutional limits
  • AST(SGOT)/ALT(SGPT) <2.5 X institutional upper limit of normal
  • creatinine ≤2.5.0
  • left ventricular ejection fraction >45%
  • FACIT-F score < 43 on screening
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

• Prior chemotherapy received in the last three months.
• Patients currently on PARP inhibitors.
• Currently taking or have taken within 10 days of enrollment.
• Patients may not be receiving any other investigational agents.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to Naltrexone or other agents used in the study.
• History of other malignancies other than nonmelanoma skin cancer, unless in complete remission and off therapy for that disease for at least 5 years.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, history of congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Any Patient with acute hepatitis and liver failure are excluded.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Single-arm study of low-dose naltrexone (LDN); Low dose Naltrexone 3 mg is taken orally once daily to be taken with food at night. Patient will be given a pill dairy to assure compliance with the medication.

Drug: Naltrexone; Naltrexone, a structurally similar compound to the opioid antagonist naloxone, but with longer half-life and higher bioavailability, was first synthesized in the 1960s and approved by Food and Drug Administration (FDA) in 1980s for treatment of opioid addiction. Its use was later expanded for management of alcohol addiction as well. The typical dose of naltrexone used for opioid and alcohol addiction is 50-100mg [19]. Naltrexone at one-tenth of the original addiction treatment dose, referred to as LDN, exhibits interesting paradoxical pharmacology and enhances endogenous opioid production. It also showed exhibiting multiple other pharmacological effects ranging from inhibition of proliferation of cancer cells, modulating immune response there by slowing the progression of autoimmune diseases and exhibiting the inhibitory effect of pro-inflammatory cytokines thereby reducing the symptoms of neuropathic and non-cancer related pain.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Characterize mitochondrial bioenergetics after ADT and the remediating effects of LDN	30 months
Characterize inflammation after ADT and the remediating effects of LDN	30 months
Characterize oxidative stress after ADT and the remediating effects of LDN	30 months
Assess the impact of low-dose naltrexone (LDN) on Cancer-related fatigue as measured by the FACIT-F questionnaire	30 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Evaluate quality of life (QOL) measures [Functional Assessment of Cancer Therapy-Prostate (FACT-P) on subjects receiving LDN	30 months
Evaluate safety and tolerability of LDN by assessing the number of participants with treatment-related adverse events graded by CTCAE v5.0	30 months

Collaborators and Investigators

• Sponsor: University of Arkansas

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2029

Study Registration Dates

• First Submitted: October 29, 2025
• First Submitted That Met QC Criteria: October 31, 2025
• First Posted (Actual): November 3, 2025

Study Record Updates

• Last Update Posted (Actual): April 24, 2026
• Last Update Submitted That Met QC Criteria: April 23, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Alkaloids; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Naloxone; Morphinans; Opiate Alkaloids; Heterocyclic Compounds, Bridged-Ring; Phenanthrenes; Naltrexone
• Other Study ID Numbers: 299392

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No