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

NCT07224009 | Not Yet Recruiting Phase 2 FDA Drug

• 1 other identifier: 299392
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Metastatic Prostate Cancer

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (2)

• 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

Study Arms (1)

Single-arm study of low-dose naltrexone (LDN)

EXPERIMENTAL

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

Interventions

Naltrexone 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.

Single-arm study of low-dose naltrexone (LDN)

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Arkansas: lead

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Naltrexone

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

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

Central Study Contacts

Aaron Holley

CONTACT

5016868274; JAHolley@uams.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a single-center, single-arm study of low-dose naltrexone (LDN) in patients with metastatic prostate cancer, both castration-sensitive and castration-resistant, that have been on ADT for at least 3 months. Its overarching objective is to determine whether LDN can improve cancer-related fatigue and quality of life in this group of patients.

Study Record Dates

• First Submitted: October 29, 2025
• First Posted: November 3, 2025
• Study Start: May 1, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2029
• Last Updated: April 24, 2026

Record last verified: 2026-04