Colorectal CancerNonAANCT02521727
To Investigate Risk of Colorectal Neoplasms in First-degree Relatives of Patients With Non-advanced Adenomas
An observational study of Colorectal Cancer and Colorectal Adenoma, run by Chinese University of Hong Kong at 2 sites in Hong Kong.
Trial summary
The risk of CRC in families of patients with CRC is well established, but it is less well-defined for families of patients with adenomas. Screening recommendations to families when an index subject has an adenoma on colonoscopy are not clear. Read more about this study
- Who is it for?
- Ages 40 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Colorectal Cancer, Colorectal Adenoma
- Type of treatment
- Injection or infusion
- How many people
- 828 participants
- Where
- 2 sitesHong Kong
- Study dates
- 26 Nov 2015to 6 Jun 2018
- 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 40 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: siblings of Hong Kong Chinese patients with advanced neoplasm compared with a sex and age-matched control population
Who may be able to join
- First-degree relatives (aged 40 to 70 years) of individuals diagnosed with non-advanced adenoma on screening colonoscopy as Cases
- FDR of patients with negative findings on colonoscopy identified during the same study period, who are of the same age group as the studied as Cohort
Who cannot join
- A FDR history of CRC
- A family history compatible with that of Hereditary Non-polyposis Colon Cancer (HNPCC) based on the Amsterdam criteria
- Known Familial Adenomatous Polyposis (FAP) syndrome
- Patients and siblings with known inflammatory bowel disease
- Undergone colonoscopy examinations in the past 5 years
- Severe cardio-pulmonary or other medical co-morbidities that preclude safe colonoscopic examination
- Pregnancy
Trial locations and contacts
2 sites in 1 country.
Hong Kong2 sites
Alice Ho Mel Ling Nethersole Hospital
Hong Kong, 999077
Prince of Wales Hospital
Hong Kong, 999077
About this study
Official title: A Prospective Colonoscopic Study to Investigate Risk of Colorectal Neoplasms in First-degree Relatives of Patients With Non-advanced Adenomas (NonAA Study)
The risk of CRC in families of patients with CRC is well established, but it is less well-defined for families of patients with adenomas. Screening recommendations to families when an index subject has an adenoma on colonoscopy are not clear. Previous studies demonstrating an increased CRC risk in close relatives of subjects with adenomas were mostly limited by the lack of a suitable comparison group, did not offer colonoscopy to all relatives or did not have verification on true status of adenoma history in the relatives. A systematic review has reported that most studies cited for risk of CRC in relatives with adenomas have not addressed the intended question. Currently International guidelines recommended screening colonoscopy in close relatives and at a younger age when there is a proband with an adenoma, however this recommendation has not been fully supported by all societies due to the lack of robust evidence. This gap in knowledge highlights the need of well-designed and adequately powered studies to estimate the risk of colorectal neoplasms in subjects who have first-degree relatives with adenomas.
Up to 30% of average risk asymptomatic individuals 50 years or older will have at least one adenoma. Based on current guidelines, nearly half the population will be counseled to undergo a colonoscopy from 40 years old based on a positive family history of adenoma. This will have enormous burden on the healthcare system if screening is implicated in all these individuals. Secondly, not all adenomas carry the same risk. Large or villous adenomas are associated with a nearly 70% increased risk of CRC in first degree relatives (FDR) whereas small adenomas may be associated with a modest increased risk 19. It is therefore important to determine the risk of colorectal neoplasms in families of subjects with non-advanced adenomas to justify more intensive screening in these individuals. Investigators hypothesize that first-degree relatives of patients with non-advanced adenoma have an increased risk of both CRC and adenomas. Investigators aim to quantify this risk, and to identify other individual patient or neoplasm characteristics that may contribute to this increased risk. In addition, Investigators aim to determine molecular alteration profiles of colonic adenoma in siblings of patients with advanced neoplasm.
Read the detailed description
Colorectal cancer (CRC) is the third most common cancer and second leading cause of cancer death worldwide. Based on data from the Hong Kong Cancer Registry in 2012, CRC is the second most common cancer in Hong Kong. It is one of the few cancers for which there are convincing data to support the benefits of screeColorectal cancer (CRC) is the third most common cancer and second leading cause of cancer death worldwide. Based on data from the Hong Kong Cancer Registry in 2012, CRC is the second most common cancer in Hong Kong. It is one of the few cancers for which there are convincing data to support the benefits of screening. Currently the removal of adenomas is the most effective way in reducing cancer incidence and mortality. International guidelines recommend screening for individuals at an average risk of CRC from the age of 50 years.
Up to 30% of average risk asymptomatic individuals 50 years or older will have at least one adenoma. Based on current guidelines, nearly half the population will be counseled to undergo a colonoscopy from 40 years old based on a positive family history of adenoma. This will have enormous burden on the healthcare system if screening is implicated in all these individuals. Secondly, not all adenomas carry the same risk. Large or villous adenomas are associated with a nearly 70% increased risk of CRC in first degree relatives (FDR) whereas small adenomas may be associated with a modest increased risk. It is therefore important to determine the risk of colorectal neoplasms in families of subjects with non-advanced adenomas to justify more intensive screening in these individuals.
The molecular pathways leading to tumour development in familial colorectal neoplasms are likely to be different from sporadic cases. Development of new molecular based methods for early detection, prevention or treatment relies heavily on the understanding of the differences between sporadic and familial neoplasms. Identification of genetic mutations can also improve genetic diagnosis and screening protocol of an at risk population.
Investigators hypothesize that first-degree relatives of patients with non-advanced adenoma have an increased risk of both CRC and adenomas. Investigators aim to quantify this risk, and to identify other individual patient or neoplasm characteristics that may contribute to this increased risk. In addition, Investigators aim to determine molecular alteration profiles of colonic adenoma in siblings of patients with advanced neoplasm.
The risk of CRC in families of patients with CRC is well established, but it is less well-defined for families of patients with adenomas. Screening recommendations to families when an index subject has an adenoma on colonoscopy are not clear. Previous studies demonstrating an increased CRC risk in close relatives of subjects with adenomas were mostly limited by the lack of a suitable comparison group, did not offer colonoscopy to all relatives or did not have verification on true status of adenoma history in the relatives. A systematic review has reported that most studies cited for risk of CRC in relatives with adenomas have not addressed the intended question. Currently International guidelines recommended screening colonoscopy in close relatives and at a younger age when there is a proband with an adenoma, however this recommendation has not been fully supported by all societies due to the lack of robust evidence. This gap in knowledge highlights the need of well-designed and adequately powered studies to estimate the risk of colorectal neoplasms in subjects who have first-degree relatives with adenomas.
- Conditions
- Colorectal Cancer, Colorectal Adenoma
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| exposed siblings/children | Consecutive subjects with non-advanced adenomas will be identified from the colonoscopy database at Prince of Wales Hospital, Alice Ho Miu Ling Nethersole Hospital, Queen Elizabeth Hospital and the bowel cancer screening center at Siu Lek Yuen. Figure 1 illustrates subject recruitment flow chart. They will be consented to provide details on their number of FDR, their FDR contact details, and cause of death in FDR who are deceased. FDR aged 40 to 70 years of consecutive patients with newly diagnosed non-advanced adenomas confirmed from endoscopy and pathology reports will be contacted via phone and invited for an interview and a colonoscopy. COLONOSCOPY With informed consents, experienced colonoscopists (GI physicians, colorectal surgeons) will perform colonoscopy under intravenous sedation, midazolam and pethidine after adequate bowel preparation. | |
| unexposed siblings/children | Subjects (Control) FDR aged 40 to 70 years of asymptomatic average risk subjects who had undergone a colonoscopy in our bowel cancer screening programme between 2010 and 2014 and found to have a normal colonoscopy will be invited to participate by phone and invitation letters, to attend a health talk and to undergo a colonoscopy. Confounding factors including use of drugs (aspirin and non-steroidal anti-inflammatory drugs), lifestyle factors (smoking, and diet questionnaire) and history of medical conditions (obesity with calculation of body mass index, diabetes, history of cardiovascular disease) between cases and controls will be recorded. COLONOSCOPY With informed consents, experienced colonoscopists (GI physicians, colorectal surgeons) will perform colonoscopy under intravenous sedation, midazolam and pethidine after adequate bowel preparation. |
What is being measured
The primary outcome is the main question the study is designed to answer.
number of participants having advanced neoplasms.
number of participants having advanced neoplasms, (included size of adenoma ≥1cm or villous structure, or high grade dysplasia as confirmed by histological report)
Measured: one day
Secondary outcomes (4)
number of participants having colorectal neoplasms
number of participants having colorectal neoplasms as confirmed by histological report)
Measured: one day
number of participants having advanced neoplasms depending on site of non-advanced adenoma in proband
number of participants having advanced neoplasms (confirmed by histological report) based on site of non-advanced adenoma in proband
Measured: one day
number of participants having advanced neoplasms based on the gender of the proband
number of participants having advanced neoplasms based on the number of participants having advanced neoplasms (confirmed by histological report) based on the gender of the proband
Measured: one day
number of participants having advanced neoplasms based on age of the proband
number of participants having advanced neoplasms (confirmed by histological report) based on the age of the proband
Measured: one day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2015 (estimated)
- Study start26 Nov 2015
- Primary completion6 Jun 2018
- Study completion6 Jun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Chinese University of Hong KongThe sponsor's other registered studies.
- 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
- 828 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chinese University of Hong Kong
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Siew Chien NG, Chinese University of Hong Kong
- Investigators
- SIEW C NG, MD, Principal investigator, CUHK
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02521727
- Sponsor's protocol ID
- NonAA
- Acronym
- NonAA
- Status last verified
- Jul 2018
- First submitted
- 6 Aug 2015
- Last updated
- 10 Jul 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Ng SC, Kyaw MH, Suen BY, Tse YK, Wong MCS, Hui AJ, Tak HY, Lau JYW, Sung JJY, Chan FKL. Prospective colonoscopic study to investigate risk of colorectal neoplasms in first-degree relatives of patients with non-advanced adenomas. Gut. 2020 Feb;69(2):304-310. doi: 10.1136/gutjnl-2018-318117. Epub 2019 Apr 26.
PubMed 31028155
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Colonoscopic Study to Investigate Risk of Colorectal Neoplasms in First-degree Relatives of Patients With Non-advanced Adenomas (NonAA Study)
- ClinicalTrials.gov ID
- NCT02521727
- Acronym / sponsor ID
- NonAA / NonAA
- Conditions
- Colorectal Cancer, Colorectal Adenoma
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 828 participants (actual)
- Lead sponsor
- Chinese University of Hong KongUniversity, hospital or other
- Study start
- 26 Nov 2015 (actual)
- Primary completion
- 6 Jun 2018 (actual)
- Study completion
- 6 Jun 2018 (actual)
- First posted
- 13 Aug 2015 (estimated)
- 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.
The risk of CRC in families of patients with CRC is well established, but it is less well-defined for families of patients with adenomas. Screening recommendations to families when an index subject has an adenoma on colonoscopy are not clear. Previous studies demonstrating an increased CRC risk in close relatives of subjects with adenomas were mostly limited by the lack of a suitable comparison group, did not offer colonoscopy to all relatives or did not have verification on true status of adenoma history in the relatives. A systematic review has reported that most studies cited for risk of CRC in relatives with adenomas have not addressed the intended question. Currently International guidelines recommended screening colonoscopy in close relatives and at a younger age when there is a proband with an adenoma, however this recommendation has not been fully supported by all societies due to the lack of robust evidence. This gap in knowledge highlights the need of well-designed and adequately powered studies to estimate the risk of colorectal neoplasms in subjects who have first-degree relatives with adenomas.
Up to 30% of average risk asymptomatic individuals 50 years or older will have at least one adenoma. Based on current guidelines, nearly half the population will be counseled to undergo a colonoscopy from 40 years old based on a positive family history of adenoma. This will have enormous burden on the healthcare system if screening is implicated in all these individuals. Secondly, not all adenomas carry the same risk. Large or villous adenomas are associated with a nearly 70% increased risk of CRC in first degree relatives (FDR) whereas small adenomas may be associated with a modest increased risk 19. It is therefore important to determine the risk of colorectal neoplasms in families of subjects with non-advanced adenomas to justify more intensive screening in these individuals. Investigators hypothesize that first-degree relatives of patients with non-advanced adenoma have an increased risk of both CRC and adenomas. Investigators aim to quantify this risk, and to identify other individual patient or neoplasm characteristics that may contribute to this increased risk. In addition, Investigators aim to determine molecular alteration profiles of colonic adenoma in siblings of patients with advanced neoplasm.
Detailed description
Colorectal cancer (CRC) is the third most common cancer and second leading cause of cancer death worldwide. Based on data from the Hong Kong Cancer Registry in 2012, CRC is the second most common cancer in Hong Kong. It is one of the few cancers for which there are convincing data to support the benefits of screeColorectal cancer (CRC) is the third most common cancer and second leading cause of cancer death worldwide. Based on data from the Hong Kong Cancer Registry in 2012, CRC is the second most common cancer in Hong Kong. It is one of the few cancers for which there are convincing data to support the benefits of screening. Currently the removal of adenomas is the most effective way in reducing cancer incidence and mortality. International guidelines recommend screening for individuals at an average risk of CRC from the age of 50 years.
Up to 30% of average risk asymptomatic individuals 50 years or older will have at least one adenoma. Based on current guidelines, nearly half the population will be counseled to undergo a colonoscopy from 40 years old based on a positive family history of adenoma. This will have enormous burden on the healthcare system if screening is implicated in all these individuals. Secondly, not all adenomas carry the same risk. Large or villous adenomas are associated with a nearly 70% increased risk of CRC in first degree relatives (FDR) whereas small adenomas may be associated with a modest increased risk. It is therefore important to determine the risk of colorectal neoplasms in families of subjects with non-advanced adenomas to justify more intensive screening in these individuals.
The molecular pathways leading to tumour development in familial colorectal neoplasms are likely to be different from sporadic cases. Development of new molecular based methods for early detection, prevention or treatment relies heavily on the understanding of the differences between sporadic and familial neoplasms. Identification of genetic mutations can also improve genetic diagnosis and screening protocol of an at risk population.
Investigators hypothesize that first-degree relatives of patients with non-advanced adenoma have an increased risk of both CRC and adenomas. Investigators aim to quantify this risk, and to identify other individual patient or neoplasm characteristics that may contribute to this increased risk. In addition, Investigators aim to determine molecular alteration profiles of colonic adenoma in siblings of patients with advanced neoplasm.
The risk of CRC in families of patients with CRC is well established, but it is less well-defined for families of patients with adenomas. Screening recommendations to families when an index subject has an adenoma on colonoscopy are not clear. Previous studies demonstrating an increased CRC risk in close relatives of subjects with adenomas were mostly limited by the lack of a suitable comparison group, did not offer colonoscopy to all relatives or did not have verification on true status of adenoma history in the relatives. A systematic review has reported that most studies cited for risk of CRC in relatives with adenomas have not addressed the intended question. Currently International guidelines recommended screening colonoscopy in close relatives and at a younger age when there is a proband with an adenoma, however this recommendation has not been fully supported by all societies due to the lack of robust evidence. This gap in knowledge highlights the need of well-designed and adequately powered studies to estimate the risk of colorectal neoplasms in subjects who have first-degree relatives with adenomas.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| exposed siblings/children | – | –Consecutive subjects with non-advanced adenomas will be identified from the colonoscopy database at Prince of Wales Hospital, Alice Ho Miu Ling Nethersole Hospital, Queen Elizabeth Hospital and the bowel cancer screening center at Siu Lek Yuen. Figure 1 illustrates subject recruitment flow chart. They will be consented to provide details on their number of FDR, their FDR contact details, and cause of death in FDR who are deceased. FDR aged 40 to 70 years of consecutive patients with newly diagnosed non-advanced adenomas confirmed from endoscopy and pathology reports will be contacted via phone and invited for an interview and a colonoscopy. COLONOSCOPY With informed consents, experienced colonoscopists (GI physicians, colorectal surgeons) will perform colonoscopy under intravenous sedation, midazolam and pethidine after adequate bowel preparation. |
| unexposed siblings/children | – | –Subjects (Control) FDR aged 40 to 70 years of asymptomatic average risk subjects who had undergone a colonoscopy in our bowel cancer screening programme between 2010 and 2014 and found to have a normal colonoscopy will be invited to participate by phone and invitation letters, to attend a health talk and to undergo a colonoscopy. Confounding factors including use of drugs (aspirin and non-steroidal anti-inflammatory drugs), lifestyle factors (smoking, and diet questionnaire) and history of medical conditions (obesity with calculation of body mass index, diabetes, history of cardiovascular disease) between cases and controls will be recorded. COLONOSCOPY With informed consents, experienced colonoscopists (GI physicians, colorectal surgeons) will perform colonoscopy under intravenous sedation, midazolam and pethidine after adequate bowel preparation. |
Who may qualify
- Ages
- 40 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- siblings of Hong Kong Chinese patients with advanced neoplasm compared with a sex and age-matched control population
Key inclusion criteria (2 listed)
- First-degree relatives (aged 40 to 70 years) of individuals diagnosed with non-advanced adenoma on screening colonoscopy as Cases
- FDR of patients with negative findings on colonoscopy identified during the same study period, who are of the same age group as the studied as Cohort
Key exclusion criteria (7 listed)
- A FDR history of CRC
- A family history compatible with that of Hereditary Non-polyposis Colon Cancer (HNPCC) based on the Amsterdam criteria
- Known Familial Adenomatous Polyposis (FAP) syndrome
- Patients and siblings with known inflammatory bowel disease
- Undergone colonoscopy examinations in the past 5 years
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
number of participants having advanced neoplasms.
Time frame: one day
number of participants having advanced neoplasms, (included size of adenoma ≥1cm or villous structure, or high grade dysplasia as confirmed by histological report)
4 secondary outcomes
number of participants having colorectal neoplasms
Time frame: one day
number of participants having advanced neoplasms depending on site of non-advanced adenoma in proband
Time frame: one day
number of participants having advanced neoplasms based on the gender of the proband
Time frame: one day
number of participants having advanced neoplasms based on age of the proband
Time frame: one day
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 10 Jul 2018.
- Derived from this study: PubMed 31028155Ng SC, Kyaw MH, Suen BY, Tse YK, Wong MCS, Hui AJ, Tak HY, Lau JYW, Sung JJY, Chan FKL. Prospective colonoscopic study to investigate risk of colorectal neoplasms in first-degree relatives of patients with non-advanced adenomas. Gut. 2020 Feb;69(2):304-310. doi: 10.1136/gutjnl-2018-318117. Epub 2019 Apr 26.
- Individual participant dataSharing planned: No
Related trials for Colorectal Cancer
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingObservational study
Pre- and On-treatment Multi-omics Profiling of Locally Advanced Rectal Cancer
Rectal Neoplasms
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 2
Tislelizumab in People With Colorectal Cancer
Colorectal Cancer
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.
SIEW C NG, MD principal investigator
CUHK
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Colorectal Cancer and Colorectal Adenoma, run by Chinese University of Hong Kong at 2 sites in Hong Kong.
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 2 inclusion and 7 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 10 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Hong Kong. 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?
number of participants having advanced neoplasms. (time frame: one day). 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 NCT02521727, which also lists 1 linked publication.
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 10 Jul 2018.