The effect of Lithium on the inhibition of the formation of polyps in patients with familial adenomatous polyposis

Phase 1

• Conditions: Familial adenomatous polyposis; Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

• Registration Number: EUCTR2022-000240-30-NL
• Lead Sponsor: Center for Experimental and Molecular Medicine, G2 (AMC)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2022-04-08
• Last Update Posted: 25 April 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

- Male or female between the age of 18 and 35 years;
- Confirmed APC germline mutation;
- Positive family history of a classical FAP phenotype (>100 colorectal adenomas);
- Intact colon, with a minimum of 50 polyps;
- Participant is willing and able to give informed consent for participation
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 12
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

- Participation in any other clinical intervention study; observational trials accepted;
- Lithium use prior to participation of the study;
- Pregnancy, breast-feeding or no use of anticonception;
- No normal intestinal mucosa left for normal tissue biopsy;
- Indication for colectomy within 2 years;
- Known renal impairment, defined as GFR < 60 ml/min;
- Known severe cardiac disorder;
- Known severe brain injury;
- Hypothyroidism;
- Hyponatremia, defined as Na < 130mmol/L;
- Positive family history of Brugada syndrome
- Co-medication known for interacting with Lithium (as defined in the protocol).
- Regular NSAID use (defined as more than twice a week for 4 consecutive weeks) within 3 months prior to baseline;
- Use of immunosuppressive or anti-inflammatory drugs within 3 months prior to baseline;
- Use of any other FAP directed drug therapy within 3 months prior to baseline (use of any alternative supplements e.g. turmeric or fish-oil must be noted in questionnaire).

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main 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. ;Secondary Objective: /;Primary end point(s): -Clone sizes will be quantified as proportions of the crypt circumference positive for NOTUM (in parts of eight, 1:8 to 8:8). When a whole crypt is positive for NOTUM (8:8), this crypt is fixed (crypt fixation).;Timepoint(s) of evaluation of this end point: every 6 months (t=0m, t=6m, t=12m, t=18m)

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): -Difference in number and size of polyps between baseline and end of study<br>-Patient reported side effects of Lithium using a Lithium side effect questionnaire (see appendix 2 of the protocol) <br>-Safety outcomes by analysing reported adverse events, physical examination and laboratory findings.<br>;Timepoint(s) of evaluation of this end point: every 6 months (t=0m, t=6m, t=12m, t=18m)