Biomarker/BioSensor development using Modulife to achieve intestinal healing in Crohn*s disease

The increasing incidence of Crohn*s disease causes considerable morbidity and
poses challenges for our health care due to costs of
therapy/hospitalisation/surgery. We and others have shown in randomized trials
that dietary self-management using the Crohn*s Disease Exclusion Diet (CDED)
phase 1 and 2 + Partial Enteral Nutrition (PEN) can induce remission in
children and adults, increase quality of life and reduce the need for
immune-suppressing medication.
While CDED phase 1 and 2 are now included in European guidelines (presented at
ESPEN 2022 and published ECCO/ESPGHAN 2020) as an alternative to Exclusive
Enteral Nutrition (EEN), the CDED maintenance phase (phase 3) still lacks a
strong evidence-base regarding the introduction of new foods once remission is
achieved. The recently completed paediatric DIETOMICS trial and the first adult
CDED study by Yanai et al. have shown clinical benefit of this approach, both
in terms of maintenance of remission and mucosal healing (only Yanai et al.).
We aim to assess the efficacy of CDED + PEN phase 3 compared to a normal diet
with standard-of-care (SOC) maintenance treatment in patients with
mild-to-moderate CD.

To date, disease management is guided by markers of inflammation in blood and
feces together with relapse of symptoms. Therefore, a secondary aim is to
observationally study heart-rate-variability (HRV) as a potential non-invasive
biomarker for active disease.

In this study, we are looking at the effectiveness of following phase 3, the
maintenance phase, of the Crohn's Disease Exclusion Diet (CDED) compared to
normal diet (with or without standard maintenance treatment) in children and
adults with mild to moderate Crohn's Disease. Secondarily, we want to
investigate whether we can use Heart Rate Variability (HRV) measurement, as a
non-invasive measurable indicator of active disease and remission during the
first 12 weeks of the CDED.

This is an interventional open-label Randomized Controlled Trial where patients
with clinical remission with CDED + PEN at week 12 (with or without stable
concomitant treatment) will be randomized to continue CDED phase 3 as
maintenance therapy (group A), or resume their normal diet (group B).

1. RCT: CDED phase 3 (maintenance phase) for patients after remission with CDED
phase 1 and 2 as induction of remission or as adjuvant concomitant treatment
(to ongoing standard of care stable treatment)
2. Observational: Firstbeat biosensor
- Weeks 0-12: continued optional biosensor use for all participants

For some patients, following CDED + PEN will help avoid medication altogether.
For patients already requiring immune suppressive medication, our approach may
yield better control with their current treatment and avoid escalation or
changing of expensive immune-suppression therapy. The potential benefit of the
trial is that of better control of CD symptoms with a therapy that has no
medical complications. Study burden consists of maintaining dietary records,
optional use of a heart-rate-monitor + the accompanying app to assess HRV and
stress-score, assessment of intestinal healing at baseline, week 6, 12, and 24
by means of ultrasounds and more frequent stool collection for calprotectin.