## Protocol Section
### Identification Module
**NCT ID:** NCT05279079

**Acronym:** MAP-1

**Brief Title:** Markers in Acute Pancreatitis-1

**Official Title:** International Prospective Evaluation of Novel Biomarkers to Detect and Predict the Severity of Drug- Associated Acute Pancreatitis in Adults

#### Organization Study ID Info
**ID:** UoL001572
#### Organization
**Class:** OTHER
**Full Name:** University of Liverpool
### Status Module
#### Completion Date
**Date:** 2024-07

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2022-03-15

**Type:** ACTUAL

**Last Update Submit Date:** 2022-03-03

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2024-01

**Type:** ESTIMATED

#### Start Date
**Date:** 2022-03

**Type:** ESTIMATED

**Status Verified Date:** 2022-03

#### Study First Post Date
**Date:** 2022-03-15
**Type:** ACTUAL
**Study First Submit Date:** 2022-02-18
**Study First Submit QC Date:** 2022-03-03
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** Innovative Medicines Initiative

**Class:** UNKNOWN

**Name:** TransBioLine Consortium

**Class:** OTHER_GOV

**Name:** Liverpool University Hospitals NHS Foundation Trust

**Class:** UNKNOWN

**Name:** Klinikum der Universität München

**Class:** OTHER

**Name:** Hospital Regional de Malaga

#### Lead Sponsor

**Class:** OTHER

**Name:** University of Liverpool

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** Prospective, multi-national, multi-centre observational diagnostic study of novel microRNA and protein biomarkers in peripheral blood and/or urine to detect and predict the severity of drug-associated acute pancreatitis (AP), with comparison of the same biomarkers in patients with acute pancreatitis from other causes, chronic pancreatitis, pancreatic cancer, diabetes mellitus and healthy volunteers.

**Detailed Description:** The MAP-1 study is designed to validate microRNA and/or pancreatic digestive enzyme biomarkers for the detection and severity assessment of drug-associated AP, for application to the assessment of adverse reactions to drugs in development or drugs already developed for other indications. The study will also assess the clinical utility of these biomarkers in AP from other causes, but is not designed to determine whether the biomarkers could be used in place of amylase and/or lipase in the standard clinical diagnosis of AP or to distinguish between the many differential diagnoses of AP. Selection is in progress of the microRNAs and pancreatic digestive enzyme biomarkers to be validated in this study, this selection being made from prospectively biobank samples obtained in a separate observational study that has separate ethical approval.

The pre-selected microRNAs and pancreatic digestive enzymes will be measured in the blood and urine of patients on admission to hospital with drug-associated acute pancreatitis (Group 1, 75 participants in receipt of one or more drugs on a defined list of drugs associated with acute pancreatitis) or other cause acute pancreatitis (Group 2, 250 participants not in receipt of any of the defined drugs). The same biomarkers will also be measured in blood and urine samples from contrast groups of patients with chronic pancreatitis (Group 3, 25 participants), pancreas cancer (Group 4, 25 participants), type I or II diabetes mellitus (Group 5, 25 participants) and healthy volunteers (Group 6, 100 participants). All participants will be at least 18 years old. MicroRNAs will be measured by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and pancreatic enzymes by mass spectrometry.

### Conditions Module

**Conditions:**

- Acute Pancreatitis Drug-Induced

### Design Module

#### Bio Spec

**Description:** Blood samples (10 ml in ethylene diamine tetra-acetic acid, EDTA, 8.5 ml in serum separator tube, SST, 2.5 ml in RNA PAXgene) and urine samples (50 ml collected in Falcon or other tube) will be taken at a single sampling time point from individuals in all groups. These samples will be taken on hospital admission from recruited patients in Groups 1 and 2. Further blood samples (10 ml in EDTA, 8.5 ml in SST and 2.5 ml in RNA PAXgene) will be taken at Day 4 (+/- 1 day) and Day 14 (+/- 2 days) from participants in Groups 1 and 2 from within the United Kingdom.

**Retention:** SAMPLES_WITH_DNA

#### Design Info

**Observational Model:** OTHER

**Time Perspective:** PROSPECTIVE

#### Enrollment Info

**Count:** 500

**Type:** ESTIMATED

**Study Type:** OBSERVATIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Drug-associated AP: patients aged 18 or more years undergoing drug treatment that has a defined risk of AP prior to and at the onset of AP

**Intervention Names:**

- Diagnostic Test: Assessment of accuracy of microRNA and pancreatic enzyme markers in blood and/or urine in the detection and/or prediction of severity of drug-associated acute pancreatitis

**Label:** Group 1

#### Arm Group 2

**Description:** Other cause AP: patients aged 18 or more years not undergoing drug treatment that has a defined risk of AP prior to and at the onset of AP

**Intervention Names:**

- Diagnostic Test: Assessment of accuracy of microRNA and pancreatic enzyme markers in blood and/or urine in the detection and/or prediction of severity of drug-associated acute pancreatitis

**Label:** Group 2

#### Arm Group 3

**Description:** Chronic pancreatitis: patients aged 18 or more years with symptomatic chronic pancreatitis confirmed by CT or MRI

**Intervention Names:**

- Diagnostic Test: Assessment of accuracy of microRNA and pancreatic enzyme markers in blood and/or urine in the detection and/or prediction of severity of drug-associated acute pancreatitis

**Label:** Group 3

#### Arm Group 4

**Description:** Pancreas cancer: patients aged 18 or more years with biopsy proven pancreas cancer

**Intervention Names:**

- Diagnostic Test: Assessment of accuracy of microRNA and pancreatic enzyme markers in blood and/or urine in the detection and/or prediction of severity of drug-associated acute pancreatitis

**Label:** Group 4

#### Arm Group 5

**Description:** Diabetes mellitus: patients aged 18 or more years with type 1 or type 2 diabetes mellitus in receipt of insulin or oral hypoglycaemics

**Intervention Names:**

- Diagnostic Test: Assessment of accuracy of microRNA and pancreatic enzyme markers in blood and/or urine in the detection and/or prediction of severity of drug-associated acute pancreatitis

**Label:** Group 5

#### Arm Group 6

**Description:** Healthy volunteers

**Intervention Names:**

- Diagnostic Test: Assessment of accuracy of microRNA and pancreatic enzyme markers in blood and/or urine in the detection and/or prediction of severity of drug-associated acute pancreatitis

**Label:** Group 6

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Group 1

- Group 2

- Group 3

- Group 4

- Group 5

- Group 6

**Description:** Panel of microRNA and pancreatic enzyme biomarkers

**Name:** Assessment of accuracy of microRNA and pancreatic enzyme markers in blood and/or urine in the detection and/or prediction of severity of drug-associated acute pancreatitis

**Type:** DIAGNOSTIC_TEST

### Outcomes Module

#### Primary Outcomes

**Description:** Scale of change from normal (healthy volunteer values) of a panel of microRNAs measured in blood and urine samples from patients with mild, moderate or severe drug-associated AP during the first 24 hours of admission, confirming specificity by comparison with results from patients with other pancreatic diseases

**Measure:** MicroRNA panel

**Time Frame:** Day of admission

#### Secondary Outcomes

**Description:** Scale of change from normal (healthy volunteer values) of a selected pancreatic enzyme biomarker in blood and/or urine taken from patients with mild, moderate or severe drug-associated AP during the first 24 hours of admission, confirming specificity by comparison with results from patients with other pancreatic diseases

**Measure:** Pancreatic enzyme biomarker

**Time Frame:** Day of admission

**Description:** Scale of change of circulating microRNAs measured in blood samples on Day 4 (+/- 1 day) and Day 14 (+/- 2 days) after admission to assess progression of AP

**Measure:** MicroRNA panel

**Time Frame:** Days 4 and 14 after admission

**Description:** Determination of AP severity will be made according to the Revised Atlanta Classification

**Measure:** Severity of AP

**Time Frame:** Within 90 days of admission

**Description:** Application of the PAtieNt-rePoRted OutcoMe scale in acute pancreatItis - an international proSpEctive cohort study (PAN-PROMISE) scale

**Measure:** Patient reported outcome

**Time Frame:** Days 4 and 14

**Description:** Progress of recruitment of patients into MAP-1

**Measure:** Progress of MAP-1

**Time Frame:** Two years

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

1. Drug-associated AP: patients ≥18 years old undergoing drug treatment that has a defined risk of AP prior to and at the onset of AP and admitted to recruiting hospitals with a diagnosis of AP established by two of: (i) typical continuous upper abdominal pain (in this study for up to 2 days in duration prior to admission); (ii) amylase and/or lipase 3 or more times the upper limit of normal; (iii) characteristic findings on abdominal imaging (if undertaken urgently by computerised tomography scan (CT) or magnetic resonance imaging (MRI); and who undergo their first study blood sampling within 24 hours of admission to hospital.
2. Other cause AP: patients ≥18 years old not undergoing drug treatment that has a defined risk of AP and admitted to recruiting hospitals with a diagnosis of AP established by two of: (i) typical continuous upper abdominal pain (in this study for up to 2 days in duration prior to admission); (ii) amylase and/or lipase 3 or more times the upper limit of normal; (iii) characteristic findings on abdominal imaging (if undertaken urgently by CT or MRI) and undergo their first study blood sampling within 24 hours of hospital admission.
3. Chronic pancreatitis: patients with symptomatic chronic pancreatitis and diagnostic abnormalities identified by CT and/or MRI and who undergo study blood sampling as an outpatient.
4. Pancreatic cancer: patients presenting with biopsy-proven or presumed pancreatic cancer and who undergo study blood sampling as an outpatient; in patients with a presumptive diagnosis of pancreatic cancer, blood and urine samples will be analysed after histological confirmation.
5. Diabetes mellitus: adult patients with type 1 or type 2 diabetes mellitus treated with insulin and/or oral anti-hyperglycaemic medication for at least 3 months and ongoing and who undergo study blood sampling as an outpatient.
6. Healthy volunteers: normal, healthy individuals aged ≥18 years old without evidence of systemic disease who have required no hospital intervention within the last year and received no drug treatment within the last 3 months and are severe acute respiratory distress syndrome corona virus 2 (SARS-CoV-2) negative.

Exclusion Criteria:

1. Drug-associated AP: onset of continuous abdominal pain more than 2 days prior to admission to hospital; known previous AP within the last 3 months; known chronic pancreatitis; known pancreatic or hepatobiliary malignancy; previous necrosectomy or pancreatic surgery; known prior type 1 or type 2 diabetes mellitus. Patients will not be excluded if they are undergoing drug treatment that has a defined risk of AP prior to and at the onset of AP and an alternative cause for AP is identified (including after recruitment and blood sampling).
2. Other cause AP: undergoing drug treatment that has a defined risk of AP (such patients should be considered for recruitment into Group 2); onset of continuous abdominal pain more than 2 days prior to admission to hospital; known previous AP within the last 3 months; known chronic pancreatitis; known pancreatic or hepatobiliary malignancy; previous necrosectomy or pancreatic surgery; type 1 or type 2 diabetes mellitus.
3. Chronic pancreatitis: hospital admission with AP within the last three months; known pancreatic or hepatobiliary malignancy; previous necrosectomy or pancreatic surgery; type 1 or type 2 diabetes mellitus.
4. Pancreatic cancer: hospital admission with AP within the last 3 months; known chronic pancreatitis; previous necrosectomy or pancreatic surgery and/or chemotherapy prior to sampling; type 1 or type 2 diabetes mellitus.
5. Diabetes mellitus: hospital admission with AP within the last 3 months; known type 3c diabetes mellitus; known history of acute or chronic pancreatitis; known history of cystic fibrosis, known history of pancreatic or hepatobiliary malignancy; known history of necrosectomy or pancreatic surgery; gestational diabetes mellitus; monogenic diabetes mellitus syndromes; post-transplantation diabetes mellitus; diabetes mellitus attributed to drugs or toxins.
6. Healthy volunteers: abnormal physical examination, abnormal routine haematology, urea, electrolytes and/or liver function tests; evidence of systemic disease; solid or haematological neoplasia within the last 5 years; hospital intervention within last 12 months; scheduled drug treatment within last 3 months and/or as required drug treatment within the last 4 weeks; infection or other sources of acute inflammation within the last 3 months.

**Healthy Volunteers:** True

**Minimum Age:** 18 Years

**Sampling Method:** NON_PROBABILITY_SAMPLE

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

**Study Population:** Adult participants aged 18 years or more, comprised of 6 Groups:

Group 1: Drug-associated AP Group 2: Other cause AP Group 3: Chronic pancreatitis Group 4: Pancreas Cancer Group 5: Diabetes mellitus Grouip 6: Healthy volunteers

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** r.sutton@liverpool.ac.uk

**Name:** Robert Sutton, MD FRCS PhD

**Phone:** +44 (0)151 795 8024

**Role:** CONTACT

**Contact 2:**

**Email:** latawiec@liverpool.ac.uk

**Name:** Diane Latawiec, MSc PGCert

**Phone:** +44 (0)151 794 9951

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Liverpool

**Contacts:**

***Contact 1:***

- **Email:** r.sutton@liverpool.ac.uk

- **Name:** Robert Sutton, MD FRCS PhD

- **Role:** CONTACT

***Contact 2:***

- **Email:** latawiec@liverpool.ac.uk

- **Name:** Diane Latawiec, MSc PGCert

- **Role:** CONTACT

**Country:** United Kingdom

**Facility:** Royal Liverpool University Hospital

**State:** Merseyside

**Zip:** L7 8XP

#### Overall Officials

**Official 1:**

**Affiliation:** University of Liverpool

**Name:** Robert Sutton, MD FRCS PhD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** UNDECIDED

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000010182

- Term: Pancreatic Diseases

- ID: D000004066

- Term: Digestive System Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC06

- Name: Digestive System Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M13115

- Name: Pancreatitis

- Relevance: HIGH

- As Found: Pancreatitis

- ID: M13102

- Name: Pancreatic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M7255

- Name: Digestive System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M8883

- Name: Gastrointestinal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T170

- Name: Acute Graft Versus Host Disease

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000010195

- Term: Pancreatitis

### Intervention Browse Module - Browse Branches

- Abbrev: Hypo

- Name: Hypoglycemic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Gast

- Name: Gastrointestinal Agents

### Intervention Browse Module - Browse Leaves

- ID: M10365

- Name: Insulin

- Relevance: LOW

- As Found: Unknown

- ID: M10054

- Name: Hypoglycemic Agents

- Relevance: LOW

- As Found: Unknown

- ID: M173166

- Name: Insulin, Globin Zinc

- Relevance: LOW

- As Found: Unknown

- ID: M22554

- Name: Pancrelipase

- Relevance: LOW

- As Found: Unknown

- ID: M13114

- Name: Pancreatin

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-24
