Familial Adenomatous PolyposesNCT03346980
Endoscopic Evaluation of Duodenal Polyposis in Patients With Familial Adenomatous Polyposis (FAP)
An observational study of Familial Adenomatous Polyposes and Duodenal Polyposis, run by Copenhagen University Hospital, Hvidovre at 1 site in Denmark.
Trial summary
Familial adenomatous polyposis (FAP) is an autosomal dominant genetic disorder that predisposes to a number or malignant disorders [1,2]. Clinically, FAP presents with an abnormal number of colorectal polyps (100-5000), while it genetically is defined by mutations in the APC-gene [1]. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Familial Adenomatous Polyposes, Duodenal Polyposis, Duodenal Cancer
- What is being tested?
- Esophagogastroduodenoscopy
- How many people
- 36 participants
- Where
- 1 siteDenmark
- Study dates
- 1 Dec 2017to 23 Jan 2020
- How long will I take part?
- 1 Year
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: The Danish Polyposis Register is sited at Copenhagen University Hospital Hvidovre. From this registry consecutive FAP patients referred for esophagogastroduodenoscopy (EGD) will prospectively be enrolled in this single-center study. Both patients referred for endoscopic surveillance and interventional endoscopy are eligible.
Who may be able to join
- Patients known with FAP (having either an APC mutation, or >100 colorectal adenomas and a positive family history) and with an indication of EGD as part of their surveillance or therapeutic program.
Who cannot join
- Patients, in whom the standard biopsy protocol cannot be fulfilled due to vital anticoagulant therapy, liver failure etc.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Endoscopic Evaluation of Duodenal Polyposis in Patients With Familial Adenomatous Polyposis (FAP) - a Single Center Prospective Validation of the Spigelman Classification
Familial adenomatous polyposis (FAP) is an autosomal dominant genetic disorder that predisposes to a number or malignant disorders [1,2]. Clinically, FAP presents with an abnormal number of colorectal polyps (100-5000), while it genetically is defined by mutations in the APC-gene [1]. Historically, colorectal cancer has been the major cause of deaths for FAP patient. However, as the incidence of colorectal cancer has decreased with the use of prophylactic colectomy, the incidence of duodenal cancer has increased [3,4]. It is estimated that the cumulative lifetime risk of duodenal polyposis exceeds 95% [1,5]. The predictor of duodenal cancer is duodenal polyposis, which is almost inevitable in patients with FAP.
In 1989 the Spigelman score was introduced in order to assess the severity of duodenal polyposis and stratify patients according to risk of duodenal cancer (Table 1) [6]. It is a composite score that includes two endoscopic parameters (number and maximum size of polyps, respectively) and two histopathological parameters (histological subtype and grade of dysplasia). The score ranges from 0-12 and it has been classified in four stages. The 10-year risk of developing duodenal cancer corresponds with the Spigelman stage ranging from ≈0 for stage 0-1 to 36% for stage 4 [7]. Besides duodenal cancer, the indications of cancer prophylactic surgical resection are debatable, but generally recommended in the case of Spigelman stage 4 or high-grade dysplasia.
Read more
Table 1 Spigelman Classification for duodenal polyposis Criterion 1 point 2 points 3 points Polyp number 1-4 5-20 >20 Polyp size (mm) 1-4 5-10 >20 Histology Tubular Tubulovillous Villous Dysplasia Low grade* High grade* Stage 0: 0 points; stage I: 1-4 points; stage II: 5-6 points; stage III: 7-8 points; stage IV: 9-12 points. *Originally, 3 grades of dysplasia were incorporated.
While the correlation to cancer has been explored in several studies, the validation and the reproducibility of the Spigelman score remains somewhat unclear. The primary aim of this study is to assess the inter- and intra-observer agreement of the Spigelman score for experienced endoscopists using state-of-the-art high-definition (HD) endoscopes.
Hypothesis: The Spigelman score has perfect reproducibility for endoscopic experts (κ>0.80 with 95% CI.).
Read the detailed description
The Danish Polyposis Register is sited at Copenhagen University Hospital Hvidovre. From this registry consecutive FAP patients referred for esophagogastroduodenoscopy (EGD) will prospectively be enrolled in this single-center study. Both patients referred for endoscopic surveillance and interventional endoscopy are eligible.
All patients will be evaluated with both standard HD gastroscope and side-viewing duodenoscope; the latter to ensure proper visualization of the major papilla. Movie sequences will be saved for post-procedural evaluation. Any sedation or buscopan administered will be registered. A biopsy protocol according to the attached CRF will be followed carefully and furthermore, if any interventional procedures are carried out, they will be registered as well as the presence of any gastric adenomas. In general, the approach is considered standard care and the study does not differ from the treatment algorithm and the national guidelines.
Post-procedural, the movies will be evaluated by three expert endoscopists all having long-term experience with FAP patients. In order to assess the inter-observer agreement of the Spigelman score, the endoscopic sub-scores by the three experts will be combined with the histopathological data. Furthermore, the inter-observer agreement of the endoscopic sub-scores will be analyzed separately. To assess the intra-observer agreement, after a minimum of one week one of the expert endoscopists will undertake a second evaluation of the movies after they have been randomized. The precise same methodology will be carried out for three novices. All clinical details will be erased from the movies before evaluation.
Design: A blinded single-center prospective observation and methodology study with subsequent calculation of intra-and inter-observer variability.
Statistical method: Intra-and inter-observer agreements between 3 operators at for the Spigelman score are calculated by weighted kappa statistics (inter class correlation).
Patients: A complete sample-size calculation has been made for the inter-observer study of the 3 observers for the Spigelman Score. To estimate an expected ICC of 0.9 being significantly higher than a threshold at 0.8 with power of 0.8 and a one-sided significance level of 0.05, 33 patients need to be enrolled in the study per protocol.
- Being tested
- Esophagogastroduodenoscopy
- Keywords
- Spigelman
- Medical subject headings
- Adenomatous Polyposis Coli, Duodenal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EsophagogastroduodenoscopyDiagnostic test
All patients will be evaluated with both standard HD gastroscope and side-viewing duodenoscope; the latter to ensure proper visualization of the major papilla.
| Study group | Role | What they receive |
|---|---|---|
| Familial adenomatous polyposis | The Danish Polyposis Register is sited at Copenhagen University Hospital Hvidovre. From this registry consecutive familial adenomatous polyposis patients referred for esophagogastroduodenoscopy (EGD) will prospectively be enrolled in this single-center study. Both patients referred for endoscopic surveillance and interventional endoscopy are eligible. Receives: Diagnostic Test: Esophagogastroduodenoscopy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Inter-observer agreement of the Spigelman Score evaluated by expert endoscopists.
The score ranges from 0-12 and it has been classified in four stages. The 10-year risk of developing duodenal cancer corresponds with the Spigelman stage ranging from ≈0 for stage 0-1 to 36% for stage 4. Stage 0: 0 points; stage I: 1-4 points; stage II: 5-6 points; stage III: 7-8 points; stage IV: 9-12 points.
Measured: 1 week
Secondary outcomes (3)
Inter- and intra-observer agreement of the endoscopic sub-scores evaluated by expert endoscopists (the number of polyps and the size of these)
The endoscopic subscores (the number of polyps and the size of these) will be analyzed separately.
Measured: 1 week
Intra-observer agreement of Spigelman Score evaluated by expert endoscopists.
The score ranges from 0-12 and it has been classified in four stages. The 10-year risk of developing duodenal cancer corresponds with the Spigelman stage ranging from ≈0 for stage 0-1 to 36% for stage 4. Stage 0: 0 points; stage I: 1-4 points; stage II: 5-6 points; stage III: 7-8 points; stage IV: 9-12 points.
Measured: 1 week
Inter- and intra-observer agreement of the Spigelman Score and the endoscopic sub-scores evaluated by novices.
The score ranges from 0-12 and it has been classified in four stages. The 10-year risk of developing duodenal cancer corresponds with the Spigelman stage ranging from ≈0 for stage 0-1 to 36% for stage 4. Stage 0: 0 points; stage I: 1-4 points; stage II: 5-6 points; stage III: 7-8 points; stage IV: 9-12 points. The endoscopic subscores (the number of polyps and the size of these) will be analyzed separately.
Measured: 1 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2017
- Study start1 Dec 2017
- Primary completion23 Jan 2020
- Study completion23 Jan 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Familial Adenomatous PolyposesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 36 participants (actual)
- Target duration
- 1 Year
Sponsor and investigators
- Lead sponsor
- Copenhagen University Hospital, Hvidovre
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, John Gasdal Karstensen, Copenhagen University Hospital, Hvidovre
- Investigators
- John G Karstensen, Principal investigator, MD, PhD
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03346980
- Sponsor's protocol ID
- SPIGELMAN-VALIDATE
- Status last verified
- Feb 2020
- First submitted
- 15 Nov 2017
- Last updated
- 13 Feb 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Vasen HF, Moslein G, Alonso A, Aretz S, Bernstein I, Bertario L, Blanco I, Bulow S, Burn J, Capella G, Colas C, Engel C, Frayling I, Friedl W, Hes FJ, Hodgson S, Jarvinen H, Mecklin JP, Moller P, Myrhoi T, Nagengast FM, Parc Y, Phillips R, Clark SK, de Leon MP, Renkonen-Sinisalo L, Sampson JR, Stormorken A, Tejpar S, Thomas HJ, Wijnen J. Guidelines for the clinical management of familial adenomatous polyposis (FAP). Gut. 2008 May;57(5):704-13. doi: 10.1136/gut.2007.136127. Epub 2008 Jan 14.
PubMed 18194984Bulow S, Bjork J, Christensen IJ, Fausa O, Jarvinen H, Moesgaard F, Vasen HF; DAF Study Group. Duodenal adenomatosis in familial adenomatous polyposis. Gut. 2004 Mar;53(3):381-6. doi: 10.1136/gut.2003.027771.
PubMed 14960520Spigelman AD, Williams CB, Talbot IC, Domizio P, Phillips RK. Upper gastrointestinal cancer in patients with familial adenomatous polyposis. Lancet. 1989 Sep 30;2(8666):783-5. doi: 10.1016/s0140-6736(89)90840-4.
PubMed 2571019
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Endoscopic Evaluation of Duodenal Polyposis in Patients With Familial Adenomatous Polyposis (FAP) - a Single Center Prospective Validation of the Spigelman Classification
- ClinicalTrials.gov ID
- NCT03346980
- Acronym / sponsor ID
- SPIGELMAN-VALIDATE
- Keywords
- Spigelman
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Copenhagen University Hospital, HvidovreUniversity, hospital or other
- Study start
- 1 Dec 2017 (actual)
- Primary completion
- 23 Jan 2020 (actual)
- Study completion
- 23 Jan 2020 (actual)
- First posted
- 20 Nov 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Familial adenomatous polyposis (FAP) is an autosomal dominant genetic disorder that predisposes to a number or malignant disorders [1,2]. Clinically, FAP presents with an abnormal number of colorectal polyps (100-5000), while it genetically is defined by mutations in the APC-gene [1]. Historically, colorectal cancer has been the major cause of deaths for FAP patient. However, as the incidence of colorectal cancer has decreased with the use of prophylactic colectomy, the incidence of duodenal cancer has increased [3,4]. It is estimated that the cumulative lifetime risk of duodenal polyposis exceeds 95% [1,5]. The predictor of duodenal cancer is duodenal polyposis, which is almost inevitable in patients with FAP.
In 1989 the Spigelman score was introduced in order to assess the severity of duodenal polyposis and stratify patients according to risk of duodenal cancer (Table 1) [6]. It is a composite score that includes two endoscopic parameters (number and maximum size of polyps, respectively) and two histopathological parameters (histological subtype and grade of dysplasia). The score ranges from 0-12 and it has been classified in four stages. The 10-year risk of developing duodenal cancer corresponds with the Spigelman stage ranging from ≈0 for stage 0-1 to 36% for stage 4 [7]. Besides duodenal cancer, the indications of cancer prophylactic surgical resection are debatable, but generally recommended in the case of Spigelman stage 4 or high-grade dysplasia.
Table 1 Spigelman Classification for duodenal polyposis Criterion 1 point 2 points 3 points Polyp number 1-4 5-20 >20 Polyp size (mm) 1-4 5-10 >20 Histology Tubular Tubulovillous Villous Dysplasia Low grade* High grade* Stage 0: 0 points; stage I: 1-4 points; stage II: 5-6 points; stage III: 7-8 points; stage IV: 9-12 points. *Originally, 3 grades of dysplasia were incorporated.
While the correlation to cancer has been explored in several studies, the validation and the reproducibility of the Spigelman score remains somewhat unclear. The primary aim of this study is to assess the inter- and intra-observer agreement of the Spigelman score for experienced endoscopists using state-of-the-art high-definition (HD) endoscopes.
Hypothesis: The Spigelman score has perfect reproducibility for endoscopic experts (κ>0.80 with 95% CI.).
Detailed description
The Danish Polyposis Register is sited at Copenhagen University Hospital Hvidovre. From this registry consecutive FAP patients referred for esophagogastroduodenoscopy (EGD) will prospectively be enrolled in this single-center study. Both patients referred for endoscopic surveillance and interventional endoscopy are eligible.
All patients will be evaluated with both standard HD gastroscope and side-viewing duodenoscope; the latter to ensure proper visualization of the major papilla. Movie sequences will be saved for post-procedural evaluation. Any sedation or buscopan administered will be registered. A biopsy protocol according to the attached CRF will be followed carefully and furthermore, if any interventional procedures are carried out, they will be registered as well as the presence of any gastric adenomas. In general, the approach is considered standard care and the study does not differ from the treatment algorithm and the national guidelines.
Post-procedural, the movies will be evaluated by three expert endoscopists all having long-term experience with FAP patients. In order to assess the inter-observer agreement of the Spigelman score, the endoscopic sub-scores by the three experts will be combined with the histopathological data. Furthermore, the inter-observer agreement of the endoscopic sub-scores will be analyzed separately. To assess the intra-observer agreement, after a minimum of one week one of the expert endoscopists will undertake a second evaluation of the movies after they have been randomized. The precise same methodology will be carried out for three novices. All clinical details will be erased from the movies before evaluation.
Design: A blinded single-center prospective observation and methodology study with subsequent calculation of intra-and inter-observer variability.
Statistical method: Intra-and inter-observer agreements between 3 operators at for the Spigelman score are calculated by weighted kappa statistics (inter class correlation).
Patients: A complete sample-size calculation has been made for the inter-observer study of the 3 observers for the Spigelman Score. To estimate an expected ICC of 0.9 being significantly higher than a threshold at 0.8 with power of 0.8 and a one-sided significance level of 0.05, 33 patients need to be enrolled in the study per protocol.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 1 Year
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Familial adenomatous polyposis | – | Diagnostic Test: EsophagogastroduodenoscopyThe Danish Polyposis Register is sited at Copenhagen University Hospital Hvidovre. From this registry consecutive familial adenomatous polyposis patients referred for esophagogastroduodenoscopy (EGD) will prospectively be enrolled in this single-center study. Both patients referred for endoscopic surveillance and interventional endoscopy are eligible. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- The Danish Polyposis Register is sited at Copenhagen University Hospital Hvidovre. From this registry consecutive FAP patients referred for esophagogastroduodenoscopy (EGD) will prospectively be enrolled in this single-center study. Both patients referred for endoscopic surveillance and interventional endoscopy are eligible.
Key inclusion criteria (1 listed)
- Patients known with FAP (having either an APC mutation, or >100 colorectal adenomas and a positive family history) and with an indication of EGD as part of their surveillance or therapeutic program.
Key exclusion criteria (1 listed)
- Patients, in whom the standard biopsy protocol cannot be fulfilled due to vital anticoagulant therapy, liver failure etc.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EsophagogastroduodenoscopyAll patients will be evaluated with both standard HD gastroscope and side-viewing duodenoscope; the latter to ensure proper visualization of the major papilla. | Diagnostic test | Familial adenomatous polyposis |
Primary outcome
Inter-observer agreement of the Spigelman Score evaluated by expert endoscopists.
Time frame: 1 week
The score ranges from 0-12 and it has been classified in four stages. The 10-year risk of developing duodenal cancer corresponds with the Spigelman stage ranging from ≈0 for stage 0-1 to 36% for stage 4. Stage 0: 0 points; stage I: 1-4 points; stage II: 5-6 points; stage III: 7-8 points; stage IV: 9-12 points.
3 secondary outcomes
Inter- and intra-observer agreement of the endoscopic sub-scores evaluated by expert endoscopists (the number of polyps and the size of these)
Time frame: 1 week
Intra-observer agreement of Spigelman Score evaluated by expert endoscopists.
Time frame: 1 week
Inter- and intra-observer agreement of the Spigelman Score and the endoscopic sub-scores evaluated by novices.
Time frame: 1 week
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2020.
- Background: PubMed 18194984Vasen HF, Moslein G, Alonso A, Aretz S, Bernstein I, Bertario L, Blanco I, Bulow S, Burn J, Capella G, Colas C, Engel C, Frayling I, Friedl W, Hes FJ, Hodgson S, Jarvinen H, Mecklin JP, Moller P, Myrhoi T, Nagengast FM, Parc Y, Phillips R, Clark SK, de Leon MP, Renkonen-Sinisalo L, Sampson JR, Stormorken A, Tejpar S, Thomas HJ, Wijnen J. Guidelines for the clinical management of familial adenomatous polyposis (FAP). Gut. 2008 May;57(5):704-13. doi: 10.1136/gut.2007.136127. Epub 2008 Jan 14.
- Background: PubMed 14960520Bulow S, Bjork J, Christensen IJ, Fausa O, Jarvinen H, Moesgaard F, Vasen HF; DAF Study Group. Duodenal adenomatosis in familial adenomatous polyposis. Gut. 2004 Mar;53(3):381-6. doi: 10.1136/gut.2003.027771.
- Background: PubMed 2571019Spigelman AD, Williams CB, Talbot IC, Domizio P, Phillips RK. Upper gastrointestinal cancer in patients with familial adenomatous polyposis. Lancet. 1989 Sep 30;2(8666):783-5. doi: 10.1016/s0140-6736(89)90840-4.
- Individual participant dataSharing planned: Undecided
Related trials for Familial Adenomatous Polyposes
RecruitingPhase 1
Testing for Safety and Colorectal Cancer Preventive Effects of ONC201
Colorectal Adenomatous Polyp, Colorectal Carcinoma
RecruitingPhase 1/2
FOG-001 in Locally Advanced or Metastatic Solid Tumors
Cancer, Colorectal Cancer
Enrolling by invitation
Investigation of β-hydroxybutyrate Supplementation as Chemoprevention in Familial Adenomatous Polyposis
FAP, Familial Adenomatous Polyposis
RecruitingPhase 2
An Investigational Drug (TPST-1495) in Patients With Familial Adenomatous Polyposis
Colorectal Carcinoma, Familial Adenomatous Polyposis
Not yet recruitingPhase 1
A Safety Study of ST316 in Participants With Familial Adenomatous Polyposis (FAP).
Familial Adenomatous Polyposis (FAP)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John G Karstensen principal investigator
MD, PhD
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Familial Adenomatous Polyposes and Duodenal Polyposis, run by Copenhagen University Hospital, Hvidovre at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Inter-observer agreement of the Spigelman Score evaluated by expert endoscopists. (time frame: 1 week). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03346980, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Feb 2020.