NCT00808743

Brief Summary

Duodenal carcinomas are the leading cause of mortality in patients with Familial Adenomatous Polyposis (FAP) who underwent prophylactic colorectal surgery. The purpose of this study is to determine wether celecoxib combined with ursodeoxycholic acid is an effective chemoprevention strategy to influence the progression of duodenal adenomas to carcinomas in patients with FAP.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
37

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started May 2009

Typical duration for phase_2

Geographic Reach
1 country

5 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 15, 2008

Completed
1 day until next milestone

First Posted

Study publicly available on registry

December 16, 2008

Completed
5 months until next milestone

Study Start

First participant enrolled

May 1, 2009

Completed
2.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2011

Completed
1.5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2013

Completed
Last Updated

May 16, 2013

Status Verified

August 1, 2010

Enrollment Period

2.2 years

First QC Date

December 15, 2008

Last Update Submit

May 15, 2013

Conditions

Keywords

Familial adenomatous polyposisAdenomatous Polyposis ColiDigestive System NeoplasmsGastrointestinal DiseaseIntestinal diseaseIntestinal neoplasmsGastrointestinal neoplasmsPolypsAdenomaAdenomatous PolypsNeoplastic Syndromes, HereditaryDigestive System DiseasesGenetic Diseases, InbornChemopreventionCelecoxibUrsodeoxycholic acidAnti-Inflammatory agents, Non-SteroidalCyclooxygenase Inhibitors

Outcome Measures

Primary Outcomes (1)

  • Change in number and size of duodenal adenomas (assessed directly and by evaluation of video and photographic material from endoscopic procedures)

    Baseline, 6 months

Secondary Outcomes (2)

  • Cell proliferation, in normal mucosa and adenomas (if present)

    Baseline, 6 months

  • Biliary acid profile (if present)

    Baseline, 6 months

Study Arms (2)

Group 1

ACTIVE COMPARATOR

Patients receive oral celecoxib twice daily and oral placebo twice daily

Drug: CelecoxibDrug: Placebo

Group 2

EXPERIMENTAL

Patients receive oral celecoxib twice daily and oral ursodeoxycholic acid twice daily

Drug: CelecoxibDrug: Ursodeoxycholic acid

Interventions

Celecoxib: 400mg twice daily, orally, 6 months

Group 1Group 2

Ursodeoxycholic acid: orally, 6 months, dosage based on body weight: below 50 kg: 1000mg, divided in two daily doses; 50-70 kg: 1500mg, divided in two daily doses; over 70 kg: 2000mg, divided in two daily doses

Group 2

Placebo: orally, 6 months, dosage based on body weight: below 50 kg: 1000mg, divided in two daily doses; 50-70 kg: 1500mg, divided in two daily doses; over 70 kg: 2000mg, divided in two daily doses

Group 1

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients with Familial adenomatous Polyposis: APC-mutation identified or more than 100 colorectal polyps on diagnosis
  • Spigelman score of duodenal adenoma equal to II or III

You may not qualify if:

  • Incapability of signing informed consent
  • Active gastric or duodenal ulcer, gastrointestinal bleeding
  • Cardiovascular disease or risk:
  • Congestive cardiac failure: NYHA class II to IV
  • Proven ischemic heart disease and/or cerebrovascular disease
  • Risk factors: hypertension, hyperlipidaemia, diabetes mellitus, family history of cardiovascular events (≥2 first degree family members \<55 years)
  • Renal dysfunction: creatinine clearance below 50mL/min
  • Liver dysfunction: albumin below 25 g/L or Child-Pugh-score equal to or below 10
  • Known allergic reaction to sulfonamides, NSAIDs or ursodeoxycholic acid
  • Use of NSAIDs or ursodeoxycholic acid for more than 1 week during the 6 months prior to the start of the study
  • Use of lithium
  • Symptomatic gallstones
  • Inflammatory bowel disease
  • (Possible) pregnancy or breast feeding

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

Academic Medical Center

Amsterdam, Netherlands

Location

University Medical Center

Groningen, Netherlands

Location

Leiden University Medical Center

Leiden, Netherlands

Location

University Medical Center St. Radboud

Nijmegen, Netherlands

Location

Erasmus Medical Center

Rotterdam, Netherlands

Location

Related Publications (2)

  • van Heumen BW, Roelofs HM, te Morsche RH, Nagengast FM, Peters WH. Duodenal mucosal risk markers in patients with familial adenomatous polyposis: effects of celecoxib/ursodeoxycholic acid co-treatment and comparison with patient controls. Orphanet J Rare Dis. 2013 Nov 19;8:181. doi: 10.1186/1750-1172-8-181.

  • van Heumen BW, Roelofs HM, Vink-Borger ME, Dekker E, Mathus-Vliegen EM, Dees J, Koornstra JJ, Langers AM, Nagtegaal ID, Kampman E, Peters WH, Nagengast FM. Ursodeoxycholic acid counteracts celecoxib in reduction of duodenal polyps in patients with familial adenomatous polyposis: a multicentre, randomized controlled trial. Orphanet J Rare Dis. 2013 Aug 6;8:118. doi: 10.1186/1750-1172-8-118.

MeSH Terms

Conditions

Adenomatous Polyposis ColiDuodenal NeoplasmsDigestive System NeoplasmsGastrointestinal DiseasesIntestinal DiseasesIntestinal NeoplasmsGastrointestinal NeoplasmsPolypsAdenomaAdenomatous PolypsNeoplastic Syndromes, HereditaryDigestive System DiseasesGenetic Diseases, Inborn

Interventions

CelecoxibUrsodeoxycholic Acid

Condition Hierarchy (Ancestors)

Neoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsColorectal NeoplasmsNeoplasms by SiteColonic DiseasesIntestinal PolyposisCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesDuodenal DiseasesPathological Conditions, AnatomicalPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

BenzenesulfonamidesSulfonamidesAmidesOrganic ChemicalsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsSulfonesSulfur CompoundsPyrazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsDeoxycholic AcidCholic AcidsBile Acids and SaltsSteroidsFused-Ring CompoundsPolycyclic CompoundsCholanes

Study Officials

  • Fokko M Nagengast, MD, Ph D

    University Medical Center St. Radboud Nijmegen, The Netherlands

    PRINCIPAL INVESTIGATOR
  • Bjorn WH van Heumen, MD

    University Medical Center St. Radboud Nijmegen, The Netherlands

    PRINCIPAL INVESTIGATOR
  • Wilbert HM Peters, Ph D

    University Medical Center St Radboud Nijmegen, The Netherlands

    PRINCIPAL INVESTIGATOR
  • Ellen Kampman, Ph D

    University Medical Center St Radboud Nijmegen, The Netherlands

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 15, 2008

First Posted

December 16, 2008

Study Start

May 1, 2009

Primary Completion

July 1, 2011

Study Completion

January 1, 2013

Last Updated

May 16, 2013

Record last verified: 2010-08

Locations