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RecruitingNCT05980221DETECTIONUpdated Aug 7, 2023

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

An interventional study of Metabolomics and 13C MTGT in Pancreatic Exocrine Insufficiency, sponsored by University Hospital Birmingham NHS Foundation Trust. Recruiting at 1 site in United Kingdom. Open to participants aged 16 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2023-08-07.

Sponsored by University Hospital Birmingham NHS Foundation Trust · Not applicable, Interventional, and Diagnostic

Phase
Not applicable
Study type
Interventional
Enrollment
150
Allocation
Non-randomized
Ages
16 Years and older
Sex
All
01

Study summary

DETECTION. The development of a metabolomic test to diagnose and quantify pancreatic exocrine insufficiency.

Read the detailed description

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.

02

Conditions studied

  • Pancreatic Exocrine Insufficiency

Keywords

  • exocrine insufficiency
  • pancreatic cancer
  • metabolomics
  • metabolites
  • chronic pancreatitis
  • cystic fibrosis
03

Who can participate

Ages eligible
16 Years and older
Sexes eligible
All
Accepts healthy volunteers
Yes

Eligibility criteria

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+
04

Study design

Phase
Not applicable
Primary purpose
Diagnostic
Allocation
Non-randomized
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
150 participants (estimated)

Study arms

  • Other
    Pancreatic cancer (main cohort)

    investigation of PEI and the metabolome of patients with pancreatic cancer in the fed and fasted state

    Diagnostic Test: Metabolomics · Diagnostic Test: 13C MTGT

  • Other
    Sub-study cohorts: Chronic pancreatitis, cystic fibrosis, NET patients on SSAs

    investigation of PEI and the metabolome of patients with other causes of PEI in the fed and fasted state

    Diagnostic Test: Metabolomics · Diagnostic Test: 13C MTGT

  • Other
    Dosing arm

    Investigation metabolome of patients pre and post initiation of PERT as part of their PEI care

    Diagnostic Test: Metabolomics · Diagnostic Test: 13C MTGT

Interventions

  • Diagnostic testMetabolomics

    Plasma samples taken for the investigation of the metabolome

  • Diagnostic test13C MTGT

    sequential breath samples taken for investigation of PEI (reference test)

    Also known as: 13C MTG breath test

05

What researchers measure

Primary outcomes

  1. 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.

    Time frame: 1 year after study completion

Secondary outcomes

  1. 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%

    Time frame: 1 year after study completion

  2. PEI status using FE-1 in comparison to the metabolome

    FE-1. Faecal elastase, diagnostic \<200

    Time frame: 1 year after study completion

  3. 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

    Time frame: 1 year after study completion

  4. 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)

    Time frame: 1 year after study completion

06

Study locations

1 of 1 sites recruiting
07

Registry details

Key details

Study ID
NCT05980221
Lead sponsor
University Hospital Birmingham NHS Foundation Trust
Collaborators
Pancreatic Cancer UK
Responsible party
Keith John Roberts (Consultant HPB and transplant surgeon, University Hospital Birmingham NHS Foundation Trust) — Principal investigator
First posted
Aug 7, 2023
Start date
Aug 24, 2020
Primary completion
Oct 2024 (estimated)
Completion
Oct 2024 (estimated)
Last update
Aug 7, 2023

Study contacts

Sarah Powell-Brett, MBChB
Contact
sarah.powell-brett1@nhs.net
07887754856
Keith Roberts, PhD
principal investigator · University Hospital Birmingham NHS Foundation Trust

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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