'Medroxyprogesterone acetate (MPA) in Familial Adenomatous Polyposis, a proof of principle study’

Rationale:
The use of progestins in combination with estrogen is associated with a reduced incidence of colorectal carcinoma (CRC)1,2. Also, incidental literature has reported a coincidence of the start of oral contraceptive agents with reduction in polyp number in a girl with Familial Adenomatous Polyposis (FAP)3. In this study we test the hypothesis that progestins may reduce reduction polyp burden in patients with Familial Adenomatous Polyposis (FAP), a familial polyposis syndrome.


Objective:

To assess in a cohort of patients with established FAP:

1 The efficacy of MPA in terms of reduction of number of colonic polyps, by means of Endoscopic Appearance of Polyposis (EAP) index.

2 The effect on histological parameters and biological response of MPA medication.


Study design:
This is an open label, proof-of-principle study in which 10 female patients will receive MPA (Provera, Pfizer BV) 10 mg/day orally for 4 months. At baseline and four months patients will undergo colonoscopy, with video recording and taking of biopsies. Videos will be assessed for Endoscopic Appearance of Polyposis (EAP) index by an expert panel of gastroenterologists. Biopsies will be assessed for cell proliferation, apoptosis and targets of progesterone signaling.


Study population:
10 female patients with established FAP and intact colon or colonic/rectal remnants, accessible by endoscopy.


Intervention:
All patients receive MPA (Provera, Pfizer BV) in a daily dosage of 10 mg for four months.


Main study parameters/endpoints:
study parameters will consist of:

1 Change in adenoma number or density.

2 Changes in biological and histological parameters.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness:

• Medication with 10 mg MPA (Provera, Pfizer BV) on a daily basis. Knowledge of nature and prevalence of side effects is largely accounted for by wide experience using this compound as an oral contraceptive agent.

• Two colonoscopies, 8 biopsies will be taken per endoscopy.

The use of progestins in combination with estrogen is associated with a reduced incidence of colorectal carcinoma (CRC)1,2. Also, incidental literature has reported a coincidence of the start of oral contraceptive agents with reduction in polyp number in a girl with Familial Adenomatous Polyposis (FAP)3. In this study we test the hypothesis that progestins may reduce reduction polyp burden in patients with Familial Adenomatous Polyposis (FAP), a familial polyposis syndrome.

Start and 4 months after start

2x colonoscopy with biopsies taken.

Treatment with MPA 10 mg/day for 4 months