Ignite Creation Date:
2024-05-06 @ 5:42 PM
Last Modification Date:
2024-10-26 @ 2:34 PM
Study NCT ID:
NCT05402891
Status:
COMPLETED
Last Update Posted:
2022-06-27
First Post:
2022-05-25
Brief Title:
The CHAMP-study The CHemopreventive Effect of Lithium in Familial AdenoMatous Polyposis
Sponsor:
Academisch Medisch Centrum - Universiteit van Amsterdam AMC-UvA
Organization:
Academisch Medisch Centrum - Universiteit van Amsterdam AMC-UvA
Study Overview
Official Title:
The Chemopreventive Effect of Lithium on Adenoma Development in Patients With Familial Adenomatous Polyposis FAP a Pilot Study
Status:
COMPLETED
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
Lithium in FAP
Brief Summary:
Rationale Familial adenomatous polyposis FAP syndrome is characterized by the development of numerous colorectal polyps If left untreated these patients have a chance of nearly 100 of developing colorectal cancer CRC at a young age Therefore guidelines recommend a prophylactic colectomy during early adulthood Even after colectomy most patients will develop adenomas in the retained rectum or ileoanal pouch requiring further endoscopic surveillance In a recent study in mouse models a chemopreventive effect of Lithium was observed on the spread of Apc mutated cells within the crypts of normal intestinal mucosa suggesting polyp formation can be prevented Lithium is used to treat patients with bipolar disorders but has never been investigated in patients with FAP aiming to reduce polyp burden We hypothesize that Lithium could reduce the spread of APC mutated cells within the crypt of normal intestinal mucosa potentially reducing polyp burden in patients with FAP
Objective The aim of this study is to investigate the effect of low-dose Lithium on stem cell dynamics the number and size of polyps and to assess safety outcomes of this drug in FAP patients
Study design A prospective phase II single arm pilot trial with a duration of 18 months The drug will be administered between month 6 and 12
Study population Twelve patients with FAP between the age of 18 and 35 not having undergone a colectomy yet having a genetically confirmed APC mutation and a family history with a classical FAP phenotype
Intervention All patients will be treated with Lithium with an oral dose of 300mg a day for six months achieving a therapeutic serum level between 02-04 mmolL
Main study parametersendpoints The main outcome parameter is the effect of Lithium on the spread of APC mutant cells within intestinal crypts over time by using an APC specific marker NOTUM a significance reduce of fixed crypts and reduction of fixed clone size of 50
Nature and extent of the burden and risks associated with participation benefit and group relatedness A physical examination and an endoscopy with biopsies will be performed at baseline and every six months four in total Laboratory testing will be done at baseline and every two months during Lithium treatment Patients will be interviewed by phone and Lithium side effect questionnaires will be obtained at baseline and during Lithium treatment Lithium serum levels will be measured at day 12 and 22 after start of the study drug at month 6 When the therapeutic range has been achieved serum level testing will be done every month Most relevant side-effects that could potential occur include polyuria hyperparathyroidism and hypothyroidism Most side effects are dose-dependent and will be regularly monitored Patients with FAP could potentially benefit from a chemopreventive therapy such as Lithium to postpone or even avoid invasive types of surgery
Objective The aim of this study is to investigate the effect of low-dose Lithium on stem cell dynamics the number and size of polyps and to assess safety outcomes of this drug in FAP patients
Study design A prospective phase II single arm pilot trial with a duration of 18 months The drug will be administered between month 6 and 12
Study population Twelve patients with FAP between the age of 18 and 35 not having undergone a colectomy yet having a genetically confirmed APC mutation and a family history with a classical FAP phenotype
Intervention All patients will be treated with Lithium with an oral dose of 300mg a day for six months achieving a therapeutic serum level between 02-04 mmolL
Main study parametersendpoints The main outcome parameter is the effect of Lithium on the spread of APC mutant cells within intestinal crypts over time by using an APC specific marker NOTUM a significance reduce of fixed crypts and reduction of fixed clone size of 50
Nature and extent of the burden and risks associated with participation benefit and group relatedness A physical examination and an endoscopy with biopsies will be performed at baseline and every six months four in total Laboratory testing will be done at baseline and every two months during Lithium treatment Patients will be interviewed by phone and Lithium side effect questionnaires will be obtained at baseline and during Lithium treatment Lithium serum levels will be measured at day 12 and 22 after start of the study drug at month 6 When the therapeutic range has been achieved serum level testing will be done every month Most relevant side-effects that could potential occur include polyuria hyperparathyroidism and hypothyroidism Most side effects are dose-dependent and will be regularly monitored Patients with FAP could potentially benefit from a chemopreventive therapy such as Lithium to postpone or even avoid invasive types of surgery
Detailed Description:
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 eg 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 p005 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 260 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 students t-test will be performed The limit for the statistical significance will be established at p 005 with a confidence interval of 95
Descriptive statistics will be used to describe the changes in outcome measures during follow-up
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 eg 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 p005 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 260 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 students t-test will be performed The limit for the statistical significance will be established at p 005 with a confidence interval of 95
Descriptive statistics will be used to describe the changes in outcome measures during follow-up
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None