Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies, the PROCEED Study

Chronic Pancreatitis Clinical Trial

Official title:

Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies (The PROCEED Study)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04753255
• Other study ID #: 2020-1058 (PA17-0104)
• Secondary ID: NCI-2021-0044120
• Status: Recruiting
• Start date: April 1, 2021
• Est. completion date: March 31, 2022

Study information

• Verified date: April 2021
• Source: M.D. Anderson Cancer Center
• Contact: Liang Li
• Phone: (713) 745-1146
• Email: lli15[@]mdanderson.org
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study gathers information on patients at different stages of chronic pancreatitis to better understand the natural course and risk factors associated with pancreatitis. Chronic pancreatitis is a disease that occurs when the pancreas is inflamed (swollen and irritated) all of the time. It is important for doctors to diagnose chronic pancreatitis in the beginning stages of the disease. Over time, as chronic pancreatitis gets worse, the pancreas may stop working correctly. Since treatment options for advanced (end-stage) chronic pancreatitis are limited, patients with early-stage chronic pancreatitis or those at high risk of developing chronic pancreatitis are ideally suited for interventions to prevent the development of end-stage chronic pancreatitis and its associated complications. Information from this study may help researchers to develop lab tests for early diagnosis and prediction of disease progression, to understand disease mechanisms, and to discover genetic factors affecting susceptibility and progression.

Description:

PRIMARY OBJECTIVES:

I. To establish a model longitudinal research cohort of adult patients for the study of chronic pancreatitis (CP) and its complications.

II. To estimate the risk of progression from suspected to definite CP, and the risk of new-onset diabetes or exocrine insufficiency in definite CP, and study how the risks are influenced by patient characteristics and conditions.

III. To test the predictive capability of candidate biomarkers for diagnosis and prognosis of CP.

IV. To develop a framework for conducting biomarker, genetic, and mechanistic studies using clinical information and the biorepository developed as part of the longitudinal research cohort.

SECONDARY OBJECTIVES:

I. In patients with suspected and definite CP, to study:

Ia. The risk of pancreatic cancer. (Clinical) Ib. The natural history of pain and its predictors (demographic, environmental, clinical, and morphological). (Clinical) Ic. Quantitative changes in quality of life and disability and their predictors (demographic, environmental, clinical, and morphological). (Clinical) Id. Composite and quantitative measures of morphological progression of CP. (Clinical) Ie. Frequency of single or composite patient-centered outcomes over time and their relationship with demographic, environmental, clinical and, morphological factors. (Clinical) If. The risk and predictors of metabolic bone disease. (Clinical) Ig. Long-term survival. (Clinical) II. To identify and validate a panel of biomarkers that discriminate patients with suspected or definite CP from the normal population and controls with unexplained upper abdominal pain but no morphological evidence of pancreatic disease. (Biomarkers and Mechanism of Disease) III. To identify and validate biomarkers that predict future development of important clinical outcomes for patients with indeterminate presentations, including progression to definite CP, occurrence of disease complications, cumulative disability, and quality of life over time. (Biomarkers and Mechanism of Disease) IV. To develop biomarkers that can define specific aspects of CP pathophysiology (including inflammation, fibrosis, acinar loss, ischemia and neuropathy) and to correlate these with disease stage and mechanisms. (Biomarkers and Mechanism of Disease) V. To develop and validate biomarkers suitable as intermediate outcome measures in therapeutic trials. (Biomarkers and Mechanism of Disease)

OUTLINE: Participants are assigned to 1 of 4 groups.

GROUP I (NO PANCREATIC DISEASE): Participants undergo collection of blood, urine, saliva, and stool samples at baseline.

GROUP II (CHRONIC UPPER ABDOMINAL PAIN): Patients undergo collection of blood, urine, saliva, and stool samples, and intravenous (IV) contrast-enhanced magnetic resonance imaging (MRI) over 1.5-2 hours and computed tomography (CT) at baseline. Patients also undergo endoscopic ultrasound (EUS) or esophagogastroduodenoscopy (EGD) with collection of pancreatic fluid samples at baseline and year 2 (in a subset of patients). Patients may also undergo collection of blood and urine samples at year 2.

GROUP III (ACUTE PANCREATITIS, RECURRENT ACUTE PANCREATITIS, OR INDETERMINE CP): Patients undergo collection of saliva and stool samples at baseline, and collection of blood and urine at baseline and yearly for years 1-4. Patient also undergo contrast-enhanced MRI over 1.5-2 hours at baseline, and years 1 and 3, and IV contrast-enhanced CT at baseline, and years 2 and 4. Patients also undergo EUS or EGD with collection of pancreatic fluid samples at baseline and year 2 (in a subset of patients).

GROUP IV (DEFINITE CP): Patients undergo collection of saliva and stool samples at baseline, and collection of blood and urine at baseline and yearly for years 1-4. Patients also undergo EUS or EGD with collection of pancreatic fluid samples at baseline. Patients also undergo IV contrast-enhanced CT and MRI over 1.5-2 hours at baseline and years 1 and 3, and bone mineral density scan over 15 minutes at baseline and years 2 and 4.

Patients in Groups II to IV are followed up yearly for 20 years.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1820
• Est. completion date: March 31, 2022
• Est. primary completion date: March 31, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• ALL GROUPS: All participants must sign an informed consent indicating that they are aware of the investigational nature of this study and willing to undergo study interventions, and authorizing the use of their protected health information for research purposes

• ALL GROUPS: Meet one set of group-specific inclusion criteria listed below

• ALL GROUPS: All participants must be >= 18 years old and =< 75 years at the time of enrollment

• NO PANCREATIC DISEASE: No personal history or symptoms of pancreatic disease

• NO PANCREATIC DISEASE: No upper abdominal symptoms

• NO PANCREATIC DISEASE: No family history of pancreatic disorders, celiac disease, cystic fibrosis

• NO PANCREATIC DISEASE: No history of acute infectious or inflammatory conditions requiring medical treatment or evaluation in the preceding 6 months (per provider clinical judgment)

• NO PANCREATIC DISEASE: No history of cancer, except for non-melanoma skin cancers

• NO PANCREATIC DISEASE: No known pregnancy at the time of enrollment

• NO PANCREATIC DISEASE: No solid organ transplant or history of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS)

• NO PANCREATIC DISEASE: Able to provide an informed consent

• NO PANCREATIC DISEASE: Not currently incarcerated

• NO PANCREATIC DISEASE: American Society of Anesthesiologists (ASA) 1-2

• CHRONIC UPPER ABDOMINAL PAIN: Referred to a pancreas or gastrointestinal (GI) clinic or admitted to the hospital for evaluation of unexplained upper abdominal pain of at least 3 months in duration for which a pancreatic origin is clinically considered in the differential diagnosis

• Pancreatic type pain is defined as epigastric pain that is often constant, often worsens postprandially, and may radiate to the back. This can often be associated with lipase/amylase elevations that do not meet the threshold for diagnosis of acute pancreatitis (AP) (i.e. < 3-fold upper limit of normal)

• CHRONIC UPPER ABDOMINAL PAIN: No history of AP or CP

• CHRONIC UPPER ABDOMINAL PAIN: No prior endoscopic sphincterotomy or pancreatic surgery

• CHRONIC UPPER ABDOMINAL PAIN: Normal cross-sectional abdominal imaging (CT and MRI/Magnetic resonance cholangiopancreatography [MRCP])

• CT and MRI/MRCP must be performed =< 24 months prior to enrollment OR within 6 months after study enrollment. CT and MRI scans must be intravenous contrast-enhanced and MRCP with secretin (a non-contrast MRI and MRCP without secretin prior to enrollment is acceptable at baseline to be used for enrollment). If the patient has had only one imaging study, the patient is eligible for enrollment as "Chronic Abdominal Pain - Undifferentiated". The second imaging study can be performed in this situation after the enrollment and the final assignment into the appropriate subgroup can be done after review of the imaging results. If the second study was planned within 6 months after enrollment but could not be completed, it will not be considered as eligibility violation and attempts will be made to complete this during follow- up as feasible. If the second study could not be performed, the subject will be assigned to chronic upper abdominal pain group if the available study was normal or as indeterminate CP if the available study shows Cambridge 1-2 findings

• INDETERMINATE CP: Referred to a pancreas or GI clinic or admitted to the hospital for evaluation of unexplained upper abdominal pain of at least 3 months in duration for which a pancreatic origin is clinically considered in the differential diagnosis

• Pancreatic type pain is defined as epigastric pain that is often constant, often worsens postprandially, and may radiate to the back. This can often be associated with lipase/amylase elevations that do not meet the threshold for diagnosis of AP (i.e. < 3-fold upper limit of normal)

• INDETERMINATE CP: No history of AP or CP

• AP is defined as compatible symptoms (upper abdominal pain) together with A) >= 3-fold elevation of serum amylase and/or lipase above upper limit of normal, AND/OR B) features of AP on cross-sectional imaging (CT and/or MR)

• INDETERMINATE CP: Cambridge grade I-II changes of CP on cross-sectional imaging (CT or MRI/MRCP)

• CT and MRI/MRCP must be performed =< 24 months prior to enrollment OR within 6 months after study enrollment. CT and MRI scans must be intravenous contrast-enhanced and MRCP with secretin (a non-contrast MRI and MRCP without secretin prior to enrollment is acceptable at baseline to be used for enrollment). If the patient has had only one imaging study, the patient is eligible for enrollment as "Chronic Abdominal Pain - Undifferentiated". The second imaging study can be performed in this situation after the enrollment and the final assignment into the appropriate subgroup can be done after review of the imaging results. If the second study was planned within 6 months after enrollment but could not be completed, it will not be considered as eligibility violation and attempts will be made to complete this during follow- up as feasible. If the second study could not be performed by month 6 after enrollment, the subject will be assigned to chronic upper abdominal pain group if the available study was normal or as indeterminate CP if the available study shows Cambridge 1-2 findings

• INDETERMINATE CP: No prior endoscopic sphincterotomy or pancreatic surgery

• AP: History of one documented attack of AP in the preceding 18 months

• AP is defined as compatible symptoms (upper abdominal pain) together with A) >= 3-fold elevation of serum amylase and/or lipase above upper limit of normal, AND/OR B) features of AP on cross-sectional imaging (CT and/or MR). Patient should not have had an attack of AP in the month prior to enrollment.

• Patients should not have had an endoscopic retrograde cholangiopancreatography (ERCP) prior to the episode of AP

• AP: Pancreatitis episode is not attributable to gallstones (i.e. suspected or definite biliary etiology), medications, trauma or autoimmune pancreatitis

• AP: Pancreatic necrosis, if present, is < 50% (to be verified by a Chronic Pancreatitis, Diabetes and Pancreatic Cancer [CPDPC] site radiologist)

• AP: Cambridge grade < III changes of CP on cross-sectional imaging (CT or MRI/MRCP)

• CT and MRI/MRCP must be performed =< 24 months prior to enrollment OR within 6 months after study enrollment. CT and MRI scans must be intravenous contrast-enhanced and MRCP with secretin (a non contrast MRI and MRCP without secretin prior to enrollment is acceptable at baseline to be used for enrollment). If the patient has had only one imaging study, the patient is eligible for enrollment. The second study can be performed in this situation after the enrollment. If the second study was planned within 6 months after enrollment but could not be completed, it will not be considered as eligibility violation. Final group assignment in this situation will be based on the available study

• AP: No prior pancreatic surgery

• RECURRENT AP: Two or more documented attacks of AP separated by at least 1 month, with complete symptom resolution between the attacks.

• AP is defined as compatible symptoms (epigastric pain with nausea or vomiting) together with A) >= 3-fold elevation of serum amylase and/or lipase above upper limit of normal, AND/OR B) features of AP on cross-sectional imaging (CT and/or MR).

• Patient should not have had an ERCP prior to having first documented attack of pancreatitis

• RECURRENT AP: Cambridge grade < III changes of CP on cross-sectional imaging (CT or MRI/MRCP)

• CT and MRI/MRCP must be performed =< 24 months prior to enrollment OR within 6 months after study enrollment. CT and MRI scans must be intravenous contrast-enhanced and MRCP with secretin (a non-contrast MRI and MRCP without secretin prior to enrollment is acceptable at baseline to be used for enrollment). If the patient has had only one imaging study, the patient is eligible for enrollment. The second study can be performed in this situation after the enrollment. If the second study was planned within 6 months after enrollment but could not be completed, it will not be considered as eligibility violation. Final assignment in this situation will be based on the available study. In a rare circumstance, the last imaging patient had was > 24 months prior to enrollment. In this circumstance, the patient is still eligible for enrollment, and can undergo CT scan first, and if there is no evidence of Cambridge 3-4 findings, undergo an MRI/MRCP to fulfill entry criteria. If the planned studies could not be completed within 6 months after enrollment, the final group assignment will be in this situation will be based on the available study

• RECURRENT AP: Pancreatitis episodes are not attributable to gallstones, medications, trauma or autoimmune pancreatitis

• RECURRENT AP: No prior pancreatic surgery

• DEFINITE CP: Presence of unequivocal CP (i.e. Cambridge grade >= 3) and/or parenchymal and/or ductal calcifications by cross-sectional imaging (IV contrast-enhanced MRI/MRCP or CT) verified by the CPDPC site radiologist

• Must exclude the possibility that calcifications are vascular. Calcifications noted by EUS only (and not correlated with CT) are not included as definite CP. A non-contrast CT scan or MRI/MRCP documenting definite CP as per criteria is acceptable for enrollment

• DEFINITE CP: Pancreatic histology diagnostic of CP (including findings of fibrosis [Ammann's >= 6], chronic inflammation, and acinar loss) as verified by a CPDPC site pathologist, if pathology slides are available for review

Exclusion Criteria:

• ALL GROUPS EXCEPT NO PANCREATIC DISEASE: History of autoimmune or traumatic pancreatitis, or sentinel attack of acute necrotizing pancreatitis which results in suspected disconnected duct syndrome

• ALL GROUPS EXCEPT NO PANCREATIC DISEASE: Primary pancreatic tumors - pancreatic ductal adenocarcinoma, suspected cystic neoplasm (> 1 cms in size or main duct involvement), neuroendocrine tumors, and other uncommon tumors

• ALL GROUPS EXCEPT NO PANCREATIC DISEASE: Pancreatic metastasis from other malignancies

• ALL GROUPS EXCEPT NO PANCREATIC DISEASE: History of solid organ transplant, HIV/AIDS

• ALL GROUPS EXCEPT NO PANCREATIC DISEASE: Known isolated pancreatic exocrine insufficiency (e.g. in the absence of any eligible inclusion criteria)

• ALL GROUPS EXCEPT NO PANCREATIC DISEASE: Participants must not have medical or psychiatric illnesses or ongoing substance abuse that in the investigator's opinion would compromise their ability to tolerate study interventions or participate in longitudinal follow up

• ALL GROUPS EXCEPT NO PANCREATIC DISEASE: Patients with known abnormal creatinine (glomerular filtration rate [GFR] < 30) or renal failure (applies to patients with chronic upper abdominal pain of suspected pancreatic origin and suspected CP [yellow] subgroups)

• ALL GROUPS EXCEPT NO PANCREATIC DISEASE: Failure to agree for longitudinal follow-up

• ALL GROUPS EXCEPT NO PANCREATIC DISEASE: Known pregnancy. All participants of childbearing potential, except if post-menopausal [i.e. no menses for >= 2 years] or had a hysterectomy, bilateral tubal ligation/clip (surgical sterilization) or surgical removal of both the ovaries), must have a negative urine or serum human chorionic gonadotropin (B-HCG) pregnancy test documented within 2 days prior to any endoscopic or radiologic procedures done for research purposes. Any standard of care tests will follow institutional policies regarding pregnancy test

• ALL GROUPS EXCEPT NO PANCREATIC DISEASE: Currently incarcerated

• ALL GROUPS EXCEPT NO PANCREATIC DISEASE: Inability to get MRI/MRCP in patients with chronic abdominal pain of suspected pancreatic origin (Green II) or suspected CP(Yellow groups) at baseline (e.g. metal object in the body which precludes performance of MRI)

Related Conditions & MeSH terms

• Acute Pancreatitis
• Chronic Pancreatitis
• Pancreatitis
• Pancreatitis, Chronic

Intervention

Procedure:
• Biospecimen Collection
Undergo collection of blood, urine, saliva, stool, and/or pancreatic fluid samples
• Computed Tomography with Contrast
Undergo contrast-enhanced CT scan
• Contrast-enhanced Magnetic Resonance Imaging
Undergo contrast-enhanced MRI
• Dual X-ray Absorptiometry
Undergo bone mineral density scan
• Endoscopic Ultrasound
Undergo EUS
• Esophagogastroduodenoscopy
Undergo EGD

Other:
• Questionnaire Administration
Ancillary studies

Locations

Country	Name	City	State
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center	Houston	Texas
United States	M D Anderson Cancer Center	Houston	Texas
United States	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	Cedars Sinai Medical Center	Los Angeles	California
United States	University of Minnesota/Masonic Cancer Center	Minneapolis	Minnesota
United States	Stanford Cancer Institute Palo Alto	Palo Alto	California
United States	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania
United States	Mayo Clinic in Rochester	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
M.D. Anderson Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Risk of progression from suspected to definite chronic pancreatitis (CP)	The progression rate and the risk factors for progression will be studied by statistical methods for survival analysis, including Kaplan-Meier analysis and Cox regression model.	Up to 20 years
Primary	Risk of new-onset diabetes or exocrine insufficiency in definite CP	Will use Kaplan-Meier method and Cox regression model to study the risk of new-onset diabetes or exocrine insufficiency in definite CP and their risk factors.	Up to 20 years
Primary	Predictive capability of candidate biomarkers		Up to 20 years