Clinical trial NCT04990245: pAtient rePorted Outcomes Linked With histoLogy in Patients With uLcerative cOlitis
Official title: APOLLO Study: pAtient rePorted Outcomes Linked With histoLogy in Patients With uLcerative cOlitis
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Ulcerative Colitis
Keywords: ulcerative colitis
patient reported outcomes
histological scoring
disability
inflammatory bowel disease
Lead sponsor: Imelda GI Clinical Research Center
Sponsor class: OTHER
First posted: 2021-08-04
Enrollment: 86
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patient with ulcerative colitis and planned endoscopy as part of routine care

Brief summary: Background and rationale:

In ulcerative colitis, treating beyond endoscopic healing has shown a reduction of relapse and hospitalization, pushing for histological remission in daily clinical practice.1 However, very little is known on how histological remission is associated with patient reported outcomes (PROMs).2,3 In recent years, several questionnaires have been developed to assess what really matters to patients: symptoms and the burden UC exerts on them.4 As PROMs are getting more and more attention during drug development programs and drug approval by international organizations, including FDA and EMA, the link between objective outcome measures (endoscopic, histological, biochemical) and PROMs should therefore be better characterized.

Objectives and design:

To investigate prospectively the association of patient reported outcomes (PROMs) and biochemical, endoscopic and histological outcome measures in patients with ulcerative colitis.

Detailed description: After informed consent, patients will undergo endoscopic assessment evaluating endoscopic disease activity using established scoring systems

* Mayo endoscopic sub-score5
* Ulcerative Colitis Endoscopic Index of Severity \[UCEIS\]6 All endoscopic assessments will be recorded, allowing blinded scoring by independent endoscopists afterwards. Study protocol APOLLO - 2 During endoscopy, colonic biopsies will be taken according to standard of care from the most inflamed area of the colon and normal area if applicable, 0-60cm from the anal verge. All biopsies will be scored histologically using the Nancy Index.7 During the same study visit, clinical symptoms (Simple clinical colitis activity index \[SCCAI\]) and patient reported outcomes (PROMs) will be evaluated digitally using validated scoring systems8
* IBD disk
* PRO-2
* Visual Analogue Scale
* IBD control in case of non-remission Finally, patients will be biochemically (C-reactive protein, hemoglobin, albumin) evaluated, including measurement of drug level (infliximab, adalimumab, vedolizumab) in case of ongoing exposure to biological agents. All evaluations are part of standard-of-care. Definitions
* Endoscopic remission: Mayo endoscopic sub-score 0 AND UCEIS 0
* Endoscopic response according to

  * Mayo score: decrease in Mayo endoscopic sub-score ≥ 1
  * UCEIS: decrease in UCEIS ≥ 2
* Endoscopic improvement: Mayo endoscopic sub-score 1
* Histological remission: Nancy histological index 0
* Absence of active/acute histological inflammation: Nancy histological index 0-1
* Histological response: Nancy histological index \> 1
* PRO2 remission: stool frequency ≤ 1 (absolute stool frequency ≤ 3 OR 1-2 stools more than usual) AND rectal bleeding score of 0 (average of 3 days prior to endoscopy)
* IBD disk remission per item:

  * Abdominal pain
  * Regulating defecation
  * Interpersonal interactions
  * Education and work
  * Sleep
  * Energy
  * Emotions
  * Body Image
  * Sexual function
  * Joint pain

Eligibility criteria: INCLUSION CRITERIA:

All patients with ulcerative colitis (≥ 16 years) undergoing planned endoscopic assessment as part of standard of care between 01.07.2020 and 30.06.2021. Evidence of a personally signed and dated informed consent document (ICF) indicating that the subject has been informed of all aspects of the study.

EXCLUSION CRITERIA:

Subjects with a diagnosis of indeterminate colitis, ischemic colitis, radiation colitis, diverticular disease associated with colitis, microscopic colitis or Crohn's disease.

Subjects with clinical findings suggestive of CD (e.g. fistulae, granulomas on biopsy) are also excluded. Similar data collection within 8 weeks prior to endoscopic assessment

Primary outcomes:
measure: correlation between histological disease activity and disability
timeFrame: 1 day
Secondary outcomes:
measure: correlation between histological disease activity and patient reported outcomes
timeFrame: 1 day
measure: correlation between histological disease activity and patient reported outcomes
timeFrame: 1 day
measure: correlation between histological disease activity and patient reported outcomes
timeFrame: 1 day
measure: correlation between histological disease activity and endoscopic disease activity
timeFrame: 1 day
measure: correlation between histological disease activity and endoscopic disease activity
timeFrame: 1 day
measure: correlation between histological disease activity and biomarkers
timeFrame: 1 day
Other outcomes:
measure: correlation between histological disease activity and patient reported outcomes
timeFrame: 1 day
Locations:
city: Bonheiden
country: Belgium
facility: Imelda GI clinical research center
Study officials:
affiliation: Imelda general hospital
name: Peter Bossuyt, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Danese S, Roda G, Peyrin-Biroulet L. Evolving therapeutic goals in ulcerative colitis: towards disease clearance. Nat Rev Gastroenterol Hepatol. 2020 Jan;17(1):1-2. doi: 10.1038/s41575-019-0211-1. No abstract available.
citation: Colombel JF, Keir ME, Scherl A, Zhao R, de Hertogh G, Faubion WA, Lu TT. Discrepancies between patient-reported outcomes, and endoscopic and histological appearance in UC. Gut. 2017 Dec;66(12):2063-2068. doi: 10.1136/gutjnl-2016-312307. Epub 2016 Sep 2.
citation: Dragasevic S, Sokic-Milutinovic A, Stojkovic Lalosevic M, Milovanovic T, Djuranovic S, Jovanovic I, Rajic S, Stojkovic M, Milicic B, Kmezic S, Oluic B, Aleksic M, Pavlovic Markovic A, Popovic D. Correlation of Patient-Reported Outcome (PRO-2) with Endoscopic and Histological Features in Ulcerative Colitis and Crohn's Disease Patients. Gastroenterol Res Pract. 2020 Apr 2;2020:2065383. doi: 10.1155/2020/2065383. eCollection 2020.
citation: de Jong MJ, Huibregtse R, Masclee AAM, Jonkers DMAE, Pierik MJ. Patient-Reported Outcome Measures for Use in Clinical Trials and Clinical Practice in Inflammatory Bowel Diseases: A Systematic Review. Clin Gastroenterol Hepatol. 2018 May;16(5):648-663.e3. doi: 10.1016/j.cgh.2017.10.019. Epub 2017 Oct 23.
citation: Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, Travers S, Rachmilewitz D, Hanauer SB, Lichtenstein GR, de Villiers WJ, Present D, Sands BE, Colombel JF. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005 Dec 8;353(23):2462-76. doi: 10.1056/NEJMoa050516.
citation: Travis SP, Schnell D, Krzeski P, Abreu MT, Altman DG, Colombel JF, Feagan BG, Hanauer SB, Lichtenstein GR, Marteau PR, Reinisch W, Sands BE, Yacyshyn BR, Schnell P, Bernhardt CA, Mary JY, Sandborn WJ. Reliability and initial validation of the ulcerative colitis endoscopic index of severity. Gastroenterology. 2013 Nov;145(5):987-95. doi: 10.1053/j.gastro.2013.07.024. Epub 2013 Jul 25.
citation: Marchal-Bressenot A, Salleron J, Boulagnon-Rombi C, Bastien C, Cahn V, Cadiot G, Diebold MD, Danese S, Reinisch W, Schreiber S, Travis S, Peyrin-Biroulet L. Development and validation of the Nancy histological index for UC. Gut. 2017 Jan;66(1):43-49. doi: 10.1136/gutjnl-2015-310187. Epub 2015 Oct 13.
citation: Bossuyt P, Hoefkens E, Pouillon L. Prime Time Was Yesterday for Patient-reported Outcomes in Daily Care of Patients With Inflammatory Bowel Diseases. Clin Gastroenterol Hepatol. 2018 Nov;16(11):1839. doi: 10.1016/j.cgh.2018.05.029. No abstract available.