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

Study Overview
=================
Brief Summary
-----------------
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.

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.

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

Conditions
-----------------
Prostate Cancer

Intervention / Treatment
-----------------
* Drug: Chitosan


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion: 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. 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. 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 Able to swallow and retain oral medication ECOG performance status of 0 - 2 Ability to sign written informed consent Testosterone level <50ng/dL at time of enrollment. Age 18 or older. May have had prior radiation therapy, surgery, or cryoablation for primary prostate cancer May have had prior cytotoxic chemotherapy for metastatic prostate cancer, prior treatment with genomically-targeted agents, or Provenge Exclusion: Known allergy to chitosan or shellfish. History of receiving more than 2 classes of ADT. Chronic constipation (BM < 3x weekly), history of malabsorption or history of daily laxative use. Patients requiring medication administration with lunch or dinner or at a frequency of three or more times per day are not eligible. Current use of chitosan, sevelamer, and/or glucosamine.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chitosan dose escalation<br> | Drug: Chitosan<br>* 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.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 |