Measuring 5-ASA urinary excretion levels in healthy volunteers

5-ASA plays an pivotal role in ulcerative colitis treatment guidelines.
Medication adherence occurs when the patient carries out a therapy as intended
by the treating physician. The reported prevalence of medication non-adherence
varies from 40-91% in UC patients on 5-ASA, which leads to an increased risk
for relapse. Therefore it is important to develop methods to improve patients
adherence. The most objective way to study compliance, is to measure 5-ASA and
its metabolite(s) in biological fluids as plasma or urine. Urinary 5-ASA
excretion measurement by High performance Liquid Chromatography (HPLC) has
been previously described. To be able to interpret urinary 5-ASA excretion
levels in patients using 5-ASA, and to define urinary 5-ASA cut-off values as
primary outcome for compliance, we need to study the range and variability of
5-ASA urinary excretion in healthy individuals.

HPLC is feasible to assess the range of urinary 5-ASA excretion in healthy
individuals using different dosages of oral 5-ASA, and HPLC is able to provide
cut-off levels for (non-) compliance in persons using different dosages of
5-ASA tablets ( Mezavant®).

This observational trial will include fifteen volunteers with a 14 week follow
up period. All volunteers will follow a consecutive dosage schedule of 1200 mg
5-ASA once daily (OD), 2400 mg 5-ASA (OD) or 1200 mg twice daily (BD), 3600 mg
(OD) or 1200 mg (OD) and 2400 mg (BD), and 4800 mg 5-ASA/day (OD) or 2400 mg
(BD). All dosages will be used during 7 days, with a drug-free interval of 7
days in between dose adjustments. Entry criteria include the absence of
significant co-morbidity or use of co-medication. Written informed consent will
be obtained.

In the 14 weeks study period, volunteers will receive 5-ASA tablets
(Mezavant®) according to the study schedule either once-daily or twice daily.
Daily morning urine spot samples will be obtained and stored at -20° prior to
HPLC analysis. Volunteers will be called every week by the investigators to
make sure that they take the medicine according to their prescribed schedule,
and to question them on possible adverse events. Blood samples will be obtained
at baseline, after 2 weeks of using 5-ASA and at end of the study

The risk of participation in the current study is considered to be low since
5-ASA treatment outside this study protocol is a widely accepted first-line
treatment in IBD with few adverse events, and very small risk on a severe
adverse event. For the exact information on the use of 5-ASA, an information
brochure is added to this protocol. Healthy volunteers have to use 5-ASA
medication during 7 weeks and have to collect daily urine spot samples in the
morning. Every week they will be called by the investigators to make sure that
they take the medicine according to their prescribed schedule, and to question
them on possible adverse events. At baseline, after 2 weeks of using 5-ASA and
at end of the study a blood sample is collected.