Study of Chitosan for Pharmacologic Manipulation of AGE (Advanced Glycation Endproducts) Levels in Prostate Cancer Patients

Phase 1b/2 Study of Chitosan for Pharmacologic Manipulation of AGE (Advanced Glycation Endproducts) Levels in Prostate Cancer Patients

This study will examine the utility of chitosan for reduction of blood or tissue levels of AGEs in patients with prostate cancer who are clinically stable on androgen-deprivation therapy.

Study Overview

• Status: Terminated
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Chitosan

Detailed Description

The overall goal of this study is to identify a safe dose of the metabolic supplement, Chitosan that can help reduce AGE (advanced glycation endproducts) levels in patients with prostate cancer. Chitosan is a naturally occurring substance found in shellfish. This study will be using Chitosan prepared from the shells of cold-water shrimp. Chitosan is approved by the FDA for use in wound dressings and has been used in published clinical trials for weight loss but is not approved for the purposes of this study. AGEs are a type of metabolite, or substance, found in food and produced in the body. The researchers helping conduct this study have found a potential link between AGE levels and cancer. Participation in this study will require three study visits over the course of about 3 months. During these visits subjects will be asked to provide blood and stool samples as well as complete surveys about their quality of life.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion:

1. Confirmation of adenocarcinoma of the prostate that is documented by one of the following: pathology report or clinic note with documented history of prostate cancer.
2. Subjects must be receiving ADT with a GnRH agonist or antagonist, with or without an anti-androgen or testosterone synthesis inhibitor. The current testosterone level must be documented to be <50ng/dL at enrollment. Subjects whose ADT is interrupted may enroll or continue on study as long as the testosterone is documented to remain <50ng/dL for the entire duration of study participation. Subjects who have undergone orchiectomy are also eligible.

3. Subjects must have adequate hematologic, renal, and hepatic function at baseline, as follows:

   • Hematology parameters: ANC >1000/mcL, platelets > 100,000/mcL, Hgb >8.0gm/dL
   • Renal Function: eGFR of ≥ 45mls/min using Cockgroft and Gault formula
   • Liver Function: Total bilirubin ≤ULN, AST and ALT <1.5x ULN
4. Able to swallow and retain oral medication
5. ECOG performance status of 0 - 2
6. Ability to sign written informed consent
7. Testosterone level <50ng/dL at time of enrollment.
8. Age 18 or older.
9. May have had prior radiation therapy, surgery, or cryoablation for primary prostate cancer
10. May have had prior cytotoxic chemotherapy for metastatic prostate cancer, prior treatment with genomically-targeted agents, or Provenge

Exclusion:

1. Known allergy to chitosan or shellfish.
2. History of receiving more than 2 classes of ADT.
3. Chronic constipation (BM < 3x weekly), history of malabsorption or history of daily laxative use.
4. Patients requiring medication administration with lunch or dinner or at a frequency of three or more times per day are not eligible.
5. Current use of chitosan, sevelamer, and/or glucosamine.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• 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: Chitosan dose escalation	Drug: Chitosan; The starting dose for Chitosan is 500mg twice a day, the second dose level is 1000mg twice a day, the third dose level is 1500mg twice a day, and the fourth dose level is 2000mg twice a day. Each dose level lasts for 28 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum tolerated dose (MTD) of Chitosan in PCa subjects.	112 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in redox status (RedoxSys, serum oxidized glutathione)	112 days
Change in inflammation (plasma cytokines, Toll-like receptor signaling)	112 days
Change in insulin resistance (HOMA-IR)	112 days
Changes in bowel permeability (plasma endotoxin)	112 days
Changes in microbiome diversity (16s rDNA sequencing)	112 days
Correlate changes in serum AGE levels (pan-AGE, carboxymethyllysine, methylglyoxal	112 days
Measure the frequency of a > 30% reduction in total AGE levels from the pretreatment level.	112 days

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Investigators: Principal Investigator: Micheal Lilly, MD, Medical University of South Carolina

Study record dates

Study Major Dates

• Study Start (Actual): January 16, 2019
• Primary Completion (Actual): July 2, 2020
• Study Completion (Actual): September 7, 2021

Study Registration Dates

• First Submitted: October 15, 2018
• First Submitted That Met QC Criteria: October 18, 2018
• First Posted (Actual): October 19, 2018

Study Record Updates

• Last Update Posted (Actual): December 15, 2021
• Last Update Submitted That Met QC Criteria: December 10, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hemostatics; Coagulants; Chelating Agents; Sequestering Agents; Chitosan
• Other Study ID Numbers: 102928

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

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