Plain English Summary
Background and study aims
Type 2 diabetes is one of the most common diagnoses in Swiss family practices. The incidence of diabetes increases with age - by 75 years old, nearly 1/3 of the population has diabetes.
About 80% of pancreatic cancer patients have elevated blood sugar or diabetes. Newly discovered diabetes can be an early symptom of pancreatic cancer. Studies show that this patients already have elevated HbA1c (a marker of diabetes) levels up to 5 years prior to a pancreatic cancer diagnosis when compared to healthy individuals. This diabetes usually disappears after a successful operation on the pancreas.
Our hypothesis is that newly diagnosed diabetics or prediabetics (those who are not matching the criteria of diabetes, but have slighly elevated blood sugar) are a high-risk group for pancreatic cancer and eligible for screening. Our intention is to measure the frequency of pancreatic cancer in newly diagnosed diabetic and prediabetic patients, and to show that the combination of the urine 3-biomarker test (a new test) with serum CA 19-9 (an already used blood test) is a suitable screening method.
Who can participate?
People with newly diagnosed diabetes mellitus or newly diagnosed prediabetes. Participants should also have at least one of the risk factors for pancreatic cancer - aged over 50 years older, smokers, family history of pancreatic cancer, chronic pancreatitis or gestational diabetes.
What does the study involve?
Patient's height, weight, blood pressure and medical history will be taken and recorded by the family doctor, along with blood and urine samples. The blood and urine samples will then be used for screening for pancreatic cancer. If participants test positive for pancreatic cancer in these tests, they will have a test for kidney function. If kidney function is normal, a CT scan will be done to determine whether they have pancreatic cancer (if patients have kidney failure, they will have an MRI scan instead of a CT scan). Patients who are suspected of having pancreatic cancer after these scans will be referred to a specialist for treatment (treatment is not part of this study).
If participants test negative for pancreatic cancer in the initial tests or after the CT scan, they will be regularly screened for pancreatic cancer every 3-6 months for 2 years. If they do show symptoms of pancreatic cancer in these follow-up screenings, they will be referred to the Swiss Pancreas Center.
Where is the study run from?
Swiss Pancreas Center, Bern (Switzerland)
When is the study starting and how long is it expected to run for?
June 2016 to September 2023
Who is funding the study?
Schweizer Pankreasstiftung (Switzerland)
Who is the main contact?
Dr. med. Claudia Mellenthin
dr.mellenthin@hin.ch
Trial website
Contact information
Type
Scientific
Primary contact
Dr Claudia Mellenthin
ORCID ID
Contact details
Schänzlihalde 1
Bern
3013
Switzerland
41797543292
dr.mellenthin@hin.ch
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
DOT PANC
Study information
Scientific title
Screening a cohort of newly diagnosed diabetics and prediabetics for pancreatic cancer using a urine 3-biomarker panel (LYVE1, REG1A, TFF1) and Serum CA 19-9
Acronym
DOT PANC
Study hypothesis
Our hypothesis is that newly diagnosed diabetics or prediabetics are a high-risk group for PDAC and eligible for screening. Our intention is therefore to measure the prevalence of PDAC in newly diagnosed diabetic and prediabetic patients, and to show that the combination of the urine 3-biomarker panel with serum CA 19-9 is a suitable screening method.
Ethics approval
Ethics approval will be sought prior to recruitment
Study design
Observational exploratory regional single-centre cohort study
Primary study design
Observational
Secondary study design
Cohort study
Trial setting
GP practices
Trial type
Screening
Patient information sheet
Participant information sheet available – to be reviewed by ethics committee
Condition
Pancreatic cancer
Diabetes
Prediabetes
Intervention
Participants' personal information and medical history will be collected, along with blood and urine samples. Measurements of HbA1c and CA-19-9 will be taken from the blood and urine samples, along with a 3-biomarker panel. In those who test positive for PDAC in these first tests, serum creatinine will be measured to assess kidney function. If there is no contraindication (i.e. if kidney function is normal), a contrasted abdominal CT scan will be performed (in case of a contraindication (kidney failure), an MRI scan will be done instead). Those testing negative from the biomarker test or CT scan will have regular screening for PDAC every 3-6 months for 2 years by their family doctor.
Intervention type
Other
Phase
Drug names
Primary outcome measure
Screening prevalence of PDAC in both screened populations, determined as the proportion of screened patients who have a positive screening test for PDAC with a confirmed CT diagnosis, or diagnosed during the 2-year follow-up.
Secondary outcome measures
1. Diagnostic performance of the urine 3-biomarker panel with serum CA19-9, assessed at predefined thresholds using the numbers of true positives, false positives, true negatives and false negatives from this test.
1.1. The receiver operating characteristic (ROC)
1.2. Area under the curve (AUC)
1.3. Sensitivity
1.4. Specificity
1.5. Predictive values
1.6. Probability values
As a gold standard, we use a CT to confirm positive screening tests, and a 2-year follow-up to confirm negative tests.
2. Mean survival of PDAC patients who were diagnosed at the screening, assessed using Kaplan-Meier curves, assessed at the 2 year follow-up
3. Stage of the PDAC at diagnosis, assessed using the numbers of participants with each stage of PDAC
Overall trial start date
02/06/2016
Overall trial end date
01/09/2023
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Either:
Newly diagnosed diabetes mellitus, defined as HbA1c >6.5% (diagnosed within 1 month before inclusion)
Or:
Newly diagnosed prediabetes, defined as HbA1c > 6 % at two occasions with an interval of ≥ 6 months (second measurement within the last month)
Participants should also have one or more of the following risk factors of PDAC:
1. Aged 50 years or older
2. Smoking
3. Positive family history for PDAC
4. Status post gestational diabetes
5. Chronic pancreatitis
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
1000
Participant exclusion criteria
1. Inability to follow the procedures of the study or missing ability to provide informed consent (e.g. due to age, language, psychological factors, dementia, etc)
2. Known PDAC
3. Other preexisting gastrointestinal cancers
4. Pregnancy
5. Known severe renal insufficency (Clearance <30 ml)
6. Aged below 18 years
Recruitment start date
01/06/2019
Recruitment end date
01/09/2021
Locations
Countries of recruitment
Switzerland
Trial participating centre
Schweizer Pankreaszentrum
Schänzlihalde 1
3013 Bern
3013
Switzerland
Sponsor information
Organisation
Schweizer Pankreaszentrum/ Prof. Z'graggen
Sponsor details
Schänzlihalde 1
Bern
3013
Switzerland
+41313353939
praxis.zgraggen@hirslanden.ch
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Hospital/treatment centre
Funder name
Schweizer Pankreasstiftung
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
We plan to publish our data on the screening results as soon as the 2-year follow up of the last patient is terminated and data analysis is completed. Publications will follow the standards of STARD37 and STROBE41, to ascertain high quality reporting. Our secondary endpoint of survival will take longer to assess and will therefore be published later.
IPD sharing statement:
Data will only be shared anonymized and after we have been assured of the adequate data protection standards of the interested parties, if their intent is relevant for the goal of developing a screening program and if the reputation of the requesting research team is acceptable.
Intention to publish date
01/03/2024
Participant level data
Other
Basic results (scientific)
Publication list