Pediatric Longitudinal Cohort Study of Chronic Pancreatitis

Official Title

Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) CPDPC16-03 Pediatric Longitudinal Cohort Study of Chronic Pancreatitis

Summary:

The investigators will enroll a total of 860 patients under 18 years of age with ARP or CP. Included in the total are the 502 patients 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.

Trial Description

Primary Outcome:

  • Length of time from progression from Acute Recurrent Pancreatitis to Chronic Pancreatitis
Secondary Outcome:
  • Number of subjects with abdominal pain
  • Number of subjects with constant abdominal pain
  • Number of subjects with episodic abdominal pain
  • Number of emergency room visits subject had in the past 12 months
  • Number of emergency room visits subject had in whole life
  • Number of hospitalizations subject had in past 12 months
  • Number of hospitalizations subject had in whole life
  • Number of school days subject missed in the last month
  • Number of subjects with Exocrine Pancreatic Insufficiency
  • Number of subjects with abnormal fasting glucose
  • Number of subjects with abnormal hemoglobin A1c (HbA1c)
  • Number of subjects with abnormal oral glucose tolerance test (OGTT)

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 behavioural limitations, bodily pain, general behaviour, 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 Behavioural Checklist (CBCL), one of the most widely-used standardized measures in child psychology for evaluating maladaptive behavioural 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) behaviours. Adults >18 years old will not complete a behavioural 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:

  • Exocrine pancreatic insufficiency: defined as the presence of abnormal fecal elastase (< 100 ug/ g stool on 2 separate samples ≥ 1 month apart).
  • 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).
  • 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 DEXA scan), fat soluble vitamin deficiencies (serum vitamin levels for A, D, E, Pro Time/International Normalised Ratio and Partial Thromboplastin Time for vitamin K) and bone density (DEXA scan) in children with ARP or CP at the time of enrollment and annually thereafter. The investigators will identify patients 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 patients 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 patient will be able to give either blood or saliva. Six ml of blood will be collected from patients 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 Centre. The specimen labels provided by CPDPC include a specimen identification (ID) number and barcode. Patient 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 patient 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 centre. 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.

View this trial on ClinicalTrials.gov

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