Use of Rectal Dialysis Technique to Measure Rectal 5-ASA Levels in Healthy Volunteers Receiving Asacol

Measurement of Rectal Levels of 5-aminosalicylic Acid (5-ASA) Using a Novel In-vivo Rectal Dialysis Technique in Healthy Volunteers on Asacol

The investigators plan to develop a novel method of estimating 5-ASA levels in the rectum at a mucosal level using in vivo rectal dialysis technique towards the eventual goal of determining the optimal dosing of Asacol® that would provide therapeutic levels of 5-ASA in the left colon.

Study Overview

• Status: Terminated
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Procedure: Rectal dialysis; Drug: Rectal dialysis

Detailed Description

Asacol® is mesalazine in a pH-dependent tablet (Eudragit S) that remains intact until reaching the terminal ileum. The tablet dissolves at a pH 7 or greater, allowing mesalazine release in the terminal ileum and throughout the colon; hence, it would be anticipated that this form of 5-ASA will produce higher concentrations in the left colon in patients with active ulcerative colitis compared to other immediate release forms of 5-ASA. However, preliminary research using dynamic computer modeling and simulation predicted that patients with active ulcerative colitis (characterized by an increased stool frequency) treated with Asacol® and Lialda (another delayed release formulation) will achieve very low 5-ASA levels in the sigmoid colon and rectum. The model predicts that these 5-ASA preparations will be relatively ineffective in treating the left side of the colon in active ulcerative colitis.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Eligible subjects would be healthy males and females
• 18-45 years of age (inclusive)
• Within 20% of normal body weight at screening
• Who are able to give written informed consent.

Exclusion Criteria:

• History of any chronic illness
• Evidence of significant organic or psychiatric disease on a brief health questionnaire
• A history or presence of any condition causing malabsorption or an effect on gastrointestinal motility
• A history of any gastrointestinal surgery
• A history of acute or chronic renal insufficiency
• Pre existing liver disease
• A history of severe allergic reaction to salicylates, aminosalicylates or any of the ingredients of Asacol® tablets or a history of multiple food/drug allergies or if they are pregnant or lactating.
• Subjects will be required to refrain from any prescription or nonprescription drug or herbal products except their birth control medications for gastrointestinal disorders for 7 days prior to dosing and during the study, till its completion at the end of the fifth visit.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1200 mg Asacol once daily for 1 week; Rectal dialysis will be done after 1 week on 1200 mg asacol	Procedure: Rectal dialysis; Rectal dialysis done after 1 week on either 1200/2400 mg Asacol dose to test rectal mucosal 5-ASA levels; Drug: Rectal dialysis; Rectal dialysis done after 1 week on either 1200/2400 mg Asacol dose to test rectal mucosal 5-ASA levels
Active Comparator: 2400 mg Asacol once daily for 1 week; Rectal dialysis will be done after 1 week on 2400 mg asacol	Procedure: Rectal dialysis; Rectal dialysis done after 1 week on either 1200/2400 mg Asacol dose to test rectal mucosal 5-ASA levels; Drug: Rectal dialysis; Rectal dialysis done after 1 week on either 1200/2400 mg Asacol dose to test rectal mucosal 5-ASA levels

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Detection of 5-ASA	5-ASA to be measured using rectal dialysis technique in-vivo	2 weeks after starting Asacol

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Detected 5-ASA With Change in Ingested Asacol Dose	Comparison of 2-week and 5-week 5-ASA as measured thorugh rectal dialysis	5 weeks after starting study

Collaborators and Investigators

• Sponsor: NorthShore University HealthSystem
• Investigators: Principal Investigator: Eli D Ehrenpreis, MD, NorthShore University HealthSystem

Publications and helpful links

General Publications

• Stobaugh DJ, Deepak P, Thorpe M, Hannon B, Ehrenpreis ED. Simulated comparison of topical and oral formulations of 5-aminosalicylate for the treatment of ulcerative colitis. Inflamm Bowel Dis. 2013 Feb;19(2):301-8. doi: 10.1002/ibd.23003.
• Reissman P, Ehrenpreis ED, Cohen S, Nogueras JJ, Zaitman D, Wexner SD. Electrolyte profiles within the ileoanal pouch: measurement by an in vivo equilibrium dialysis technique. Dig Liver Dis. 2003 Apr;35(4):251-5. doi: 10.1016/s1590-8658(03)00062-8.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2012
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): December 5, 2014

Study Registration Dates

• First Submitted: December 4, 2012
• First Submitted That Met QC Criteria: July 23, 2019
• First Posted (Actual): July 25, 2019

Study Record Updates

• Last Update Posted (Actual): October 15, 2019
• Last Update Submitted That Met QC Criteria: September 27, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Aminosalicylates; Mucosal levels; Rectal dialysis
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: EH 11-364