# Chronotherapy of 5-Aminosalicylic Acid in Ulcerative Colitis: A Randomized Crossover Trial

> **NIH NIH R01** · RUSH UNIVERSITY MEDICAL CENTER · 2021 · $314,000

## Abstract

ABSTRACT
5-aminosalicylic acid (5-ASA) medications are first line treatment for mild to moderate Ulcerative Colitis (UC),
comprise 81% of all UC prescriptions, and have a market share of 1.5 billion. However, despite 5-ASA
frequency and optimization, 35% of patients fail induction therapy and 52% of patients fail to maintain
remission at 12 months, requiring step up therapy to immunomodulators or biologics which have increased
side effects and cost. This highlights a key challenge in UC which is to address the large inter- and intra-
patient variabilities in both disease progression and variability in response to treatment. Chronotherapy is the
timing of medical interventions according to the host circadian rhythms in order to optimize drug response and
minimize toxicity, and is one explanation for the large variability in response to medications. The long-term
objective of our research is to establish the hypothesis that is that appropriate time of day of administration of
oral, once daily 5-ASA therapy in alignment with the host circadian rhythms will improve subclinical
inflammation and microbial structure/function and increase mucosal 5-ASA levels. To test this hypothesis, In
response to the small R01 for pilot and feasibility clinical trials (PAS-20-160) and to test our hypothesis, we
propose to conduct a six month, single center, randomized crossover pilot trial involving 60 subjects with
inactive UC [Mayo score ≤2, endoscopic score 0-1] but subclinical inflammation [stool calprotectin > 50 mcg/g]
on a stable dose of once daily 5-ASA medication. All subjects will be randomized to once daily 5-ASA
medications two different times of the day: either between 06:00 – 10:00 h or 18:00 – 22:00 h. Three disease
assessments will performed at: 1) enrollment just before randomization; 2) month 3, at the completion of first
arm (condition 1), and 3) month 6, after completion of the second arm (condition 2). We will assess time impact
of our chronotherapy protocol on: 1) subclinical inflammation (Aim 1): a) stool calprotectin; b) intestinal barrier
integrity; and c) endoscopic/histology scores; 2) Microbiota: mucosal and stool microbiota structure and
function (Aim 2); and 3) 5-ASA metabolism: a) increase mucosal levels of 5-ASA and b) mucosal NAT activity
(Aim 3). In addition, optimal 5-ASA treatment (i.e., Aims 1-3) will depend upon host chronotype which will be
monitored by validated questionnaires, rest-wake actigraphy, and urinary melatonin. The results of this
innovative proposal will establish a key role for chronotherapy in the treatment of UC and provide pilot data for
the future larger multicenter clinical trials. Chronotherapy will allow for a personalized medicine approach that
incorporates circadian biology to improve efficacy and minimize intolerance in treatment of UC.

## Key facts

- **NIH application ID:** 10180200
- **Project number:** 1R01DK128085-01
- **Recipient organization:** RUSH UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Garth R Swanson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $314,000
- **Award type:** 1
- **Project period:** 2021-04-07 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10180200

## Citation

> US National Institutes of Health, RePORTER application 10180200, Chronotherapy of 5-Aminosalicylic Acid in Ulcerative Colitis: A Randomized Crossover Trial (1R01DK128085-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10180200. Licensed CC0.

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