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

NCT ID: NCT07224009

Last Updated: 2025-11-04

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-31
• Study Completion Date: 2029-01-31

Brief Summary

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.

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.

Conditions

Metastatic Prostate Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Naltrexone

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

University of Arkansas

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Central Contacts

Aaron Holley

Role: CONTACT

JAHolley@uams.edu

5016868274

Other Identifiers

299392

Identifier Type: -

Identifier Source: org_study_id