Pediatric Longitudinal Cohort Study of Chronic Pancreatitis
Condition: Pancreatitis, Chronic; Pancreatitis, Acute
MeSH terms: Pancreatitis; Pancreatitis, Chronic
Study type: Observational [Patient Registry]

Summary: 
      The investigators will enroll a total of 628 patients under 18 years of age with ARP or CP.
      Included in the total are the 357patients in the INSPPIRE 1 database who are planned to be
      reenrolled under this protocol over the next 4 years. Patient questionnaires and physician
      surveys will be applied at the time of enrollment and annually thereafter as long as
      possible. At the first study visit after turning 18 years of age, the patient will sign the
      informed consent to continue in the study. Specifically, the investigators will define the
      demographics of the pediatric ARP and CP cohort, describe risk factors, presence of family
      history of acute and chronic pancreatitis, diabetes and pancreatic cancer and assess disease
      burden and sequelae.
    

Detailed description: 
      Disease Burden Pain. The pattern of the pain (constant versus episodic), its frequency,
      duration, visits to the emergency room or hospitalizations for pain, impact of pain on
      quality of life will be recorded in questionnaires. The intensity of the pain will be
      measured at enrollment, during an attack and annually using FACES Pain Scale-Revised, a
      self-report questionnaire validated for children >4 y/o. The names, dosing and frequency of
      medications taken for pain will also be queried.

      Health-Related Quality of Life (HRQOL). An age-specific instrument validated for United
      States children will be used to measure HRQOL at enrollment and annually thereafter. Parents
      of children 5-18 years old will complete Child Health Questionnaire Parent Form 50 questions
      (CHQ PF-50). Children >10 years old will answer Child Health Questionnaire Child Form 87
      questions (CHQ-87). Adults >18 years old will not complete a health-related questionnaire.
      These questionnaires capture physical functioning, social, emotional, physical and behavioral
      limitations, bodily pain, general behavior, mental health, self-esteem, general health
      perceptions, change in health and parental emotional impact.

      Depression and anxiety. Depression and anxiety are strong predictors of chronic pain and
      pain-related disability in children, but it is not known whether this applies to children
      with ARP or CP. The investigators will assess for depression and anxiety in the INSPPIRE
      cohort at the time of enrollment and annually thereafter. The investigators will utilize the
      Child Behavioral Checklist (CBCL), one of the most widely-used standardized measures in child
      psychology for evaluating maladaptive behavioral and emotional problems in preschool subjects
      aged 1½ to 5 years and in school-age subjects between the ages of 6 and 18. For preschool-age
      children, the CBCL/1½-5 (completed by parents or surrogates) will be used. For school-age
      children 6-18 y/o, the investigators will utilize CBCL/6-18 y/o (completed by parents or
      surrogates). Children who are 11-18 y/o will answer a self-report questionnaire (Youth-Self
      Report Form or YSR/11-18). CBCL assesses internalizing (i.e., anxious, depressive, and over
      controlled) and externalizing (i.e., aggressive, hyperactive, noncompliant, and
      undercontrolled) behaviors. Adults >18 years old will not complete a behavioral checklist.

      Patients/parents will spend approximately 2 hours answering questionnaires; their time will
      be compensated at $50 per visit. Patients will be enrolled during clinic visit as outpatient
      or as an inpatient. Alternatively, questionnaires can be applied over the phone or completed
      at home and returned via mail if the patient is unable to travel. Self-addressed stamped
      envelopes will be given to the patient/parent as needed for returning the questionnaires.

      Disease Sequelae

      The presence of exocrine pancreatic insufficiency and glucose intolerance/diabetes will be
      monitored at the time of enrollment and annually thereafter. Monitoring will include
      specifically:

        1. Exocrine pancreatic insufficiency: defined as the presence of abnormal fecal elastase (<
           100 ug/ g stool on 2 separate samples ≥ 1 month apart) or abnormal serum trypsin or
           serum trypsinogen.

        2. Diabetes or prediabetes: Monitoring for diabetes in our cohort will include once yearly
           assessments with fasting glucose (diabetes range if ≥ 126 mg/dL), HbA1c (abnormal if >6;
           diabetic if >6.5%) and oral glucose tolerance test (OGTT). For OGTT, 1.75 grams/kg of
           standard glucose beverage (glucola, maximum 75 grams) will be consumed within 10 minutes
           at time 0. Glucose will be drawn prior to the beverage and at time 120 minutes. From
           this test, glycemic status will be defined as: (1) normal glucose tolerance (NGT,
           fasting glucose <100 mg/dL, 2 hour <140 mg/dL); (2) pre-diabetic based on impaired
           fasting glucose (IFG, fasting glucose 100-125 mg/dL) and/or impaired glucose tolerance
           (IGT, 2 hour glucose 140-199 mg/dL); or (3) diabetic (DM, fasting glucose >126 mg/dL or
           2 hour glucose >200 mg/dL).

        3. Nutritional status including micronutrient deficiency: To determine the nutritional
           sequelae of ARP or CP in children, the investigators will assess for
           malnutrition/obesity (weight, height, BMI, z scores; body fat mass and lean mass as
           measured by DXA scan), fat soluble vitamin deficiencies (serum vitamin levels for A, D,
           and E and bone density (DXA scan) in children with ARP or CP at the time of enrollment
           and annually thereafter.

      The investigators will identify subjects within our cohort that presented with acute
      recurrent pancreatitis episodes, normal exocrine and endocrine pancreas function and normal
      pancreas imaging without any signs of chronicity (ARP cohort). The investigators will
      identify the development of CP on an annual basis as long as possible, as well as development
      of sequelae and disease burden as listed above.

      Prospective Registry

      The investigators will develop a database of children with ARP and CP. This will provide a
      cohort of well-phenotyped subjects for future studies targeting pathogenesis and novel
      therapies. The investigators will establish a process by which investigators outside of the
      consortium may have access to the data and biospecimens.

      At enrollment, via the informed consent, subjects will choose whether or not to allow use of
      their biological samples for this study, future research, genetic analysis, genetic analysis
      for future research, and any type of future research. They will also choose whether or not we
      may keep their name and personal information in a registry to allow us to contact them for
      other future research.

      BIOSPECIMEN COLLECTION

      Sample collection for deoxyribonucleic acid (DNA): The subject will be able to give either
      blood or saliva. Six ml of blood will be collected from subjects in an
      ethylenediaminetetraacetic acid tube or 2 ml saliva samples in Oragene DNA collection kits
      then labeled with the barcoded specimen labels provided by the Consortium for the Study of
      Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) Coordinating Center. The
      specimen labels provided by CPDPC include a specimen identification (ID) number and barcode.
      Subject identifiers (for example names or initials) are not included on the labels. Before
      shipping the specimens to the central repository the specimen ID number from the label will
      be connected to the patient information in the CPDPC's secure IIMS Specimen Manager system.
      After the specimen ID number is linked to the subject in the CPDPC system the samples will be
      submitted to the central repository for the study via overnight courier. The central
      repository for DNA will be at the University of Iowa. The central repository at Iowa will not
      have access to the link that connects to the patient's personal identifiers in the Integrated
      Information Management System (IIMS). The central repository will log receipt of the
      specimens into the CPDPC IIMS Specimen Manager system using the specimen ID from the labeled
      vials. The central repository will process the specimens into aliquots for the extraction of
      genomic DNA following the CPDPC specimen processing described in the appendices. The aliquots
      will be labeled with CPDPC supplied labels and stored in a freezer at -80 degree Centigrade.
      The CPDPC aliquots labels contain barcodes and specimen ID numbers that do not link the
      aliquots to each other. The only link to the subject information resides in the secured
      database at the CPDPC coordinating and data management center. The central repository
      laboratory staff and the study researchers do not have access to this link. At the end of the
      study the specimens stored in the central repository at Iowa will be transferred to a central
      repository at National Institute of Diabetes and Digestive and Kidney Diseases.

      Urine collection for bio-markers: To be completed only at sites identified by the lead site
      to collect urine samples. Not all sites will be collecting urine. See Appendix 14.27 for
      collection and processing instructions. The subject will be instructed to collect a minimum
      of 50 mL clean-catch urine sample. A dipstick urine analysis will be performed immediately
      after urine collection. Urine samples will then be kept on wet ice or refrigerated until
      processed. Samples will be processed within 4 hours of collection. Samples will be labeled
      with the barcoded specimen labels provided by the CPDPC Coordinating Center. The specimen
      labels provided by CPDPC include a specimen ID number and barcode. Subject identifiers (for
      example names or initials) are not included on the labels. Before shipping the specimens to
      the central repository the specimen ID number from the label will be connected to the subject
      information in the CPDPC's secure IIMS Specimen Manager system. After processing, samples
      will be frozen at -80ºC. The urine processing log sheet will be completed. Samples will be
      stored and batch shipped to the Central repository at University of Iowa annually. The
      central repository will log receipt of the specimens into the CPDPC IIMs Specimen Manager
      system using the specimen ID from the labeled vials. The central repository at University of
      Iowa will not have access to the link that connects the subject's personal identifiers in the
      IIMS system. The central repository will log receipt of the specimens into the CPDPC IIMS
      Specimen Manager system using the specimen ID from the labeled vials. The CPDPC aliquots
      labels contain barcodes and specimen ID numbers that do not link the aliquots to each other.
      The only link to the subject information resides in the secured database at the CPDPC
      coordinating and data management center. The central repository laboratory staff and the
      study researchers do not have access to this link. At the end of the study the specimens
      stored in the central repository at Iowa will be transferred to a central repository at
      NIDDK.
    

Intervention name(s): Blood sample; Patient questionnaires; Saliva sample; Urine sample
Intervention type(s): Diagnostic Test; Behavioral; Diagnostic Test; Diagnostic Test
Intervention description(s): Six ml of blood will be collected from patients in an EDTA tube. 2 ml saliva samples in Oragene DNA collection kits; Questionnaires will be completed at the baseline and annual follow-up visits to collect data that will define the demographics of the pediatric ARP and CP cohort, describe risk factors, presence of family history of acute and chronic pancreatitis, diabetes and pancreatic cancer and assess disease burden and sequelae.; 2 ml saliva samples in Oragene DNA collection kits collected if no blood sample being collected.; 50 ml of urine in collection container.
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Children <18 years of age with acute recurrent pancreatitis or chronic pancreatitis.
      
Biospecimen description: 
      6 ml blood sample or 2 ml saliva sample collected 1 time. Urine 50 ml collected one time
    
Keywords: Pediatric; Pancreatitis; Chronic; Acute; Recurrent; ARP; CP; Pancreas; Children