New Onset of DiabetEs in aSsociation with pancreatic ductal adenocarcinoma (NODES Trial): protocol of a prospective, multicentre observational trial

Abstract

Introduction: Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis with an overall 5-year survival of approximately 8%. The success in reducing the mortality rate of PDAC is related to the discovery of new therapeutic agents, and to a significant extent to the development of early detection and prevention programmes. Patients with new-onset diabetes mellitus (DM) represent a high-risk group for PDAC as they have an eightfold higher risk of PDAC than the general population. The proposed screening programme may allow the detection of PDAC in the early, operable stage. Diagnosing more patients in the curable stage might decrease the morbidity and mortality rates of PDAC and additionally reduce the burden of the healthcare.

Methods and analysis: This is a prospective, multicentre observational cohort study. Patients ≥60 years old diagnosed with new-onset (≤6 months) diabetes will be included. Exclusion criteria are (1) Continuous alcohol abuse; (2) Chronic pancreatitis; (3) Previous pancreas operation/pancreatectomy; (4) Pregnancy; (5) Present malignant disease and (6) Type 1 DM. Follow-up visits are scheduled every 6 months for up to 36 months. Data collection is based on questionnaires. Clinical symptoms, body weight and fasting blood will be collected at each, carbohydrate antigen 19-9 and blood to biobank at every second visit. The blood samples will be processed to plasma and analysed with mass spectrometry (MS)-based metabolomics. The metabolomic data will be used for biomarker validation for early detection of PDAC in the high-risk group patients with new-onset diabetes. Patients with worrisome features will undergo MRI or endoscopic ultrasound investigation, and surgical referral depending on the radiological findings. One of the secondary end points is the incidence of PDAC in patients with newly diagnosed DM.

Ethics and dissemination: The study has been approved by the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (41085-6/2019). We plan to disseminate the results to several members of the healthcare system includining medical doctors, dietitians, nurses, patients and so on. We plan to publish the results in a peer-reviewed high-quality journal for professionals. In addition, we also plan to publish it for lay readers in order to maximalise the dissemination and benefits of this trial.

Trial registration number: ClinicalTrials.gov NCT04164602.

Keywords: general diabetes; pancreatic disease; preventive medicine; protocols & guidelines.

Conflict of interest statement

Competing interests: BK and AMG are employees of Metanomics Health GmbH, Germany.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

Flow chart of the study protocol. *Weight loss (except at visit 0), abdominal pain/discomfort, abnormal laboratory data, unstable glucose metabolism despite the adequate diet and medical treatment and without intercurrent infection (except at visit 0). **Fasted (overnight, at least 8 hours) patients’ blood samples at room temperature will be drawn into an EDTA tube. Within 2 hours after blood draw samples will be at 19°C–21°C. After centrifugation, the supernatant is carefully removed. After that, the plasma is transferred in 0.5 ml aliquots to tubes and stored at −80°C, in a dedicated freezer (≤6 hours from centrifuge to freezer). CA19-9, carbohydrate antigen 19–9; EUS, endoscopic ultrasound; GADA, glutamic acid decarboxylase antibodies.