For this study, monitoring was requested from Clinical Monitoring Center (CMC). After approval by the METC, a monitoring intake visit will be scheduled to set up a monitoring plan.
In this study, no randomisation will take place, every participant is given the same treatment.
All crypt analysis data and adenoma counts will be scored blindly.
Patients will be recruited from the large cohort of FAP patients at the hereditary GI Cancer clinic at the Amsterdam UMC. Prior to their routine surveillance colonoscopy, patients will be invited to participate by a member of the study team. In total 12 patients will be included in this trial.
Adenomatous tissue collected endoscopically, as part of routine care, will be stored according to regulations of the department of pathology in the AMC. Normal intestinal mucosa collected endoscopically, as part of study material to assess NOTUM distribution size e.g., will be analysed in the Center for Experimental and Molecular Medicine (CEMM). Source documents and CRFs will be stored by the project leader for 15 years after closure of the trial. Collected samples will be stored for 5 years. In case of informed consent is reached for participation in a biobank, samples will be stored for 15 years. Data of the subjects will be coded in order of participation. The code and the data are stored in different locations. The code can only be seen by the investigators. Qualified authorities can get insight in the code and data, but only when accompanied by the investigators. Informed consent forms are kept in separate files, to ensure the data security. The handling of personal data will comply with the Dutch Personal Data Protection Act.
Since this study is not yet been performed in humans with FAP, this study will be a pilot study. We believe a number of 12 patients is sufficient for the explorative purpose of this study. By performing a paired analysis, the effect of variation between individuals will be reduced, and we expect sufficient power to draw significant results. To detect a reduction of 50% (power stat. 80%, p=0.05) in fitness of APC-mutant cells, we need to analyse sizes of APC mutant clones within 11 partially populated crypts. To ensure sufficient material we need 840 crypts per patient per time point. A typical biopsy yields 100-250 crypts, therefore we will perform 12 biopsies in total (2 biopsies per segment, 6 segments) per patient per time point. In that way, sufficient data will be obtained to confirm or refute the study hypothesis.
Subjects who withdraw from the trial after start of Lithiumcarbonate will not be replaced.
To describe the study population, baseline characteristics and changes in outcome parameters during follow-up, descriptive statistics will be used in this study. SPSS for Windows software (Chicago, IL, USA) version 26.0 will be used for these analyses. If other statistical analysis will be used, this will be mentioned in the study paper.
Primary analysis for the primary outcome parameter will be done by analyzing the data using two-sided student's t-test. will be performed. The limit for the statistical significance will be established at p \< 0.05 with a confidence interval of 95%.
Descriptive statistics will be used to describe the changes in outcome measures during follow-up.
