Clinical trial NCT04032652: Use of Rectal Dialysis Technique to Measure Rectal 5-ASA Levels in Healthy Volunteers Receiving Asacol
Official title: Measurement of Rectal Levels of 5-aminosalicylic Acid (5-ASA) Using a Novel In-vivo Rectal Dialysis Technique in Healthy Volunteers on Asacol
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Ulcerative Colitis
Keywords: Pharmacokinetics
Aminosalicylates
Mucosal levels
Rectal dialysis
Lead sponsor: Endeavor Health
Sponsor class: OTHER
First posted: 2019-07-25
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Detection of 5-ASA
timeFrame: 2 weeks after starting Asacol
Secondary outcomes:
measure: Change in Detected 5-ASA With Change in Ingested Asacol Dose
timeFrame: 5 weeks after starting study
Other outcomes:
Locations:
Study officials:
affiliation: Endeavor Health
name: Eli D Ehrenpreis, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.