|- candidate number||3786|
|- NTR Number||NTR1393|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||4-aug-2008|
|- Secondary IDs||2007-007477-23 |
|- Public Title||'Medroxyprogesterone acetate (MPA) in Familial Adenomatous Polyposis, a proof of principle study’|
|- Scientific Title||'Medroxyprogesterone acetate (MPA) in Familial Adenomatous Polyposis, a proof of principle study’|
|- ACRONYM||MPA in FAP|
|- hypothesis||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.|
|- Healt Condition(s) or Problem(s) studied||Familial adenomatous polyposis (FAP), Medroxyprogesterone acetate (MPA)|
|- Inclusion criteria||1. Females > 14 years of age |
2. Established FAP, confirmed by prior colonoscopy
3. Patients must be able to adhere to the study visits and protocol requirements
4. Patients must be able to give written informed consent. In case of a minor, parents/legal representative must be able to give a written consent. The consent must be obtained prior to any screening procedures
|- Exclusion criteria||1. Females before menarche|
2. Prior progestin use in the past year
3. Change in the use of NSAIDs at least 3 month prior to the study
4. Allergic reaction on MPA during previous use
5. Female patients who are pregnant or breast-feeding.
6. Prior thromboflebitis or thromboembolism.
7. Previous or current serious cardiac or cerebrovascular condition. Like thromboflebitis or thromboembolism, severe hypertension, severe liverfunction disorders. A history of jaundice, herpes gestationis non-explained vaginal bleeding or deterioration of otosclerosis during pregnancy or use of female hormones.
8. Patients with fertility wish for the study period
9. Not available for follow-up assessment
|- mec approval received||yes|
|- multicenter trial||yes|
|- Type||Single arm|
|- planned startdate ||4-aug-2008|
|- planned closingdate||4-aug-2011|
|- Target number of participants||10|
|- Interventions||2x colonoscopy with biopsies taken.|
Treatment with MPA 10 mg/day for 4 months
|- Primary outcome||Change in polyp burden|
|- Secondary outcome||Biological response in the target tissue (colon)|
|- Timepoints||Start and 4 months after start|
|- Trial web site||N/A|
|- CONTACT FOR PUBLIC QUERIES||MD. Jarom Heijmans|
|- CONTACT for SCIENTIFIC QUERIES||MD. Jarom Heijmans|
|- Sponsor/Initiator ||Leiden University Medical Center (LUMC), Department of Gastroenterology and Hepatology|
(Source(s) of Monetary or Material Support)
|Leiden University Medical Center (LUMC), Department of Gastroenterology and Hepatology|
|- Brief summary||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.|
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.
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.
10 female patients with established FAP and intact colon or colonic/rectal remnants, accessible by endoscopy.
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.
|- Main changes (audit trail)|
|- RECORD||4-aug-2008 - 12-aug-2008|