The Development of a Metabolomic Test to Diagnose and Quantify Pancreatic Exocrine Insufficiency (The DETECTION Study)

Study Overview
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Brief Summary
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DETECTION. The development of a metabolomic test to diagnose and quantify pancreatic exocrine insufficiency.

Detailed Description
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Pancreatic exocrine insufficiency (PEI) is prevalent and progressive among patients with pancreatic cancer, treatment with pancreatic enzyme replacement therapy (PERT) has been proven to reduce gastrointestinal symptoms, improve quality of life and survival and is therefore recommended in NICE guidelines. Despite this, most patients with PEI do not receive PERT. One cause for under treatment is lack of a well-tolerated and accurate diagnostic test that can provide quick results. The current, most widely used test, the faecal elastase stool test, has low accuracy, particularly after surgery, and results take several days. Furthermore, the test cannot help with dosing of PERT. Metabolomics can be used to quantify metabolites in blood. These metabolites are directly influenced by normal digestion and absorption of food, for example blood lipid levels are very different in the fed and fasted states. This program of work will give a standard meal to healthy controls and patients with PEI and screen their blood before and after a test meal. Differences in the metabolic profile will be used to develop a 'fingerprint' of PEI based upon one metabolite or a combination of metabolites. The ultimate goal is to develop a simple blood test that can be used outside of specialist centres that is acceptable to patients, can accurately diagnose PEI and can guide treatment with PERT. This body of work aims to investigate the metabolome of patients with PEI (of different causes), PEI will be defined in the different cohorts by a multimodel approach with the 13C MTGT as primary reference test and FE-1 and PEI-Q used as supporting tests. A test meal will be given to fasted participants alongside baseline blood samples and breath samples. Patients will then have blood and breath taken hourly for 6 hours. Blood samples will be spun and frozen for batch metabolomic analysis.

Official Title
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The Development of a Metabolomic Test to Diagnose and Quantify Pancreatic Exocrine Insufficiency (The DETECTION Study)

Conditions
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Pancreatic Exocrine Insufficiency

Intervention / Treatment
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* Diagnostic Test: Metabolomics
* Diagnostic Test: 13C MTGT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: (for main pancreatic cancer cohort) PDAC PEI (as defined by breath test) Tolerating oral diet Inclusion Criteria: (for CF cohort) CF PEI (as defined by breath test) Tolerating oral diet Inclusion Criteria: (for CP cohort) CP PEI (as defined by breath test) Tolerating oral diet Exclusion Criteria (all arms): No other GI conditions For each arm no evidence of the other arm conditions For health controls, no history of CP, CF or pancreatic cancer No GI surgery (except pancreatic resection in the pancreatic cancer cohort) Unable to consent Unable to travel to UHB for testing Prognosis < 2months Performance status 2+

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Investigating the metabolome of patients with PEI in the fasted and fed state. Prospective, single centre, observational study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Pancreatic cancer (main cohort)<br>investigation of PEI and the metabolome of patients with pancreatic cancer in the fed and fasted state | Diagnostic Test: Metabolomics<br>* Plasma samples taken for the investigation of the metabolome<br>Diagnostic Test: 13C MTGT<br>* sequential breath samples taken for investigation of PEI (reference test)<br>* Other names: 13C MTG breath test;|
| Other: Sub-study cohorts: Chronic pancreatitis, cystic fibrosis, NET patients on SSAs<br>investigation of PEI and the metabolome of patients with other causes of PEI in the fed and fasted state | Diagnostic Test: Metabolomics<br>* Plasma samples taken for the investigation of the metabolome<br>Diagnostic Test: 13C MTGT<br>* sequential breath samples taken for investigation of PEI (reference test)<br>* Other names: 13C MTG breath test;|
| Other: Dosing arm<br>Investigation metabolome of patients pre and post initiation of PERT as part of their PEI care | Diagnostic Test: Metabolomics<br>* Plasma samples taken for the investigation of the metabolome<br>Diagnostic Test: 13C MTGT<br>* sequential breath samples taken for investigation of PEI (reference test)<br>* Other names: 13C MTG breath test;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Metabolome | metabolomic fingerprint of patient with PEI in the fed and fasted state Bloods are taken in the fed and fasted state, after centrifugation, the plasma is then frozen at -80. Samples will then be analysed using untargeted liquid chromatography mass spectrometry, after which the raw data will be processed using the open-source software XCMS. The resultant metabolite features in the samples will be compared between healthy and diseased (PEI) cohorts to identify features specific to exocrine insufficiency. | 1 year after study completion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PEI status using 13CMTGT in comparison to the metabolome | breath test (13CMTGT). 13C labelled fatty test meal ingested, exhaled breath samples eveyr hour up to 6 hours, the cumulative percent dose of 13C recovered will then be used as a marker for PEI, diagnostic under 29% | 1 year after study completion | 
| PEI status using FE-1 in comparison to the metabolome | FE-1. Faecal elastase, diagnostic <200 | 1 year after study completion | 
| PEI status using PEIQ in comparison to the metabolome | PEI-Q: Pancreatic exocrine insufficiency questionnaire (symptomatic assessment of PEI). >1.8 severe PEI, 1.4-1.8 moderate PEI, 0.6-1.4 mild PEI | 1 year after study completion | 
| Response of the fed and fasted metabolome to PERT | Investigation of the metabolome in response to PERT low dose and high dose. The metabolomic profile indicative of PEI will then be assessed in a repeat cohort of patients that reattend twice on low dose and then high dose PERT. Bloods will be taken as for the main trial, in the fed and fasted state and the metabolomic profile (determined by the main cohort) will assessed using targeted liquid chromatography mass spectrometry to investigate whether it is altered by PERT (pancreatic exocrine replacement therapy) | 1 year after study completion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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exocrine insufficiency, pancreatic cancer, metabolomics, metabolites, chronic pancreatitis, cystic fibrosis