The Effect of Vitamin D Substitution on the Development of Chronic Pancreatitis

The Effect of Vitamin D Substitution on Pancreatic Parenchyma and Development of Fibrosis After First Acute Alcoholic Pancreatitis: A Randomized Prospective Trial

Acute pancreatitis (AP) may develop to chronic pancreatitis (CP). In Finland, the ethiology is alcohol in about 80% of the cases. Several symptoms lower the quality of life in CP patients, including abdominal pain, exocrine and endocrine pancreatic insufficiency.

Recently, the investigators and others have found that vitamin D may protect from the formation of fibrosis on cellular level. The investigators hypothesized that after the first AP they may be able to protect the formation of fibrosis leading to CP with Vitamin D, and designed this RCT.

The aim is to study whether the investigators can prevent CP with vitamin D substitute.

In this randomized controlled patient study, the patients after their first AP are randomized to have either a normal recommended (10 μ) or a largest safe dose (100 μg). of vitamin D substitute daily. The patients are examined by MRI/MRCP imaging and laboratory tests at the baseline after recovery from AP and yearly then after.

Primary endpoint is the development of parenchymal changes possibly related to fibrosis. Secondary endpoints are the development of CP with Mannheim criteria, CP related complications and mortality.

The first analysis will be done after 7 years.

The enrollment will begin 26.9.2016

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Pancreatitis
• Intervention / Treatment: Dietary supplement: Vitamin D 100ug; Dietary supplement: Vitamin D 10ug

• Study Type: Interventional
• Enrollment (Anticipated): 260
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Finland
  • Tampere, Finland, 33520
    • Tampere university Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 101 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• First alcohol induced acute pancreatitis
• Willing to participate in a 3 year RCT

Exclusion Criteria:

• Renal failure
• Hypercalcemia
• High serum levels of vitamin D
• Unwilling to participate

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Vitamin D 100ug; The highest safest dose. Expected to lower risk of chronic pancreatitis after acute pancreatitis.	Dietary supplement: Vitamin D 100ug; Vitamin D 100 ug from Orion Pharma. Safest highest daily dose of vitamin D.
Placebo Comparator: Vitamin D 10ug; Placebo dose. Minimal recommended dose	Dietary supplement: Vitamin D 10ug; Placebo dose. Minimal recommended dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The development of parenchymal changes possibly related to fibrosis after acute pancreatitis analysed by magnetic resonance cholangiopancreatography imaging texture analysis	A radiologist analyses the pancreatic parenchymal changes from MRCP images	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The development of chronic pancreatitis (CP) with Mannheim criteria	The diagnostic Mannheim criteria include laboratory tests for measuring the endocrine and exocrine function of the pancreas and MRI/MRCP for measuring pancreatic duct lesions and calcifications.	3 years
The development of complications related to chronic pancreatitis	The complications are registered from the participants medical records.	3 years
Mortality related to chronic pancreatitis	The mortality is registered from the participants medical records.	3 years

Collaborators and Investigators

• Sponsor: Tampere University Hospital
• Collaborators: Orion Corporation, Orion Pharma

Publications and helpful links

General Publications

• Sherman MH, Yu RT, Engle DD, Ding N, Atkins AR, Tiriac H, Collisson EA, Connor F, Van Dyke T, Kozlov S, Martin P, Tseng TW, Dawson DW, Donahue TR, Masamune A, Shimosegawa T, Apte MV, Wilson JS, Ng B, Lau SL, Gunton JE, Wahl GM, Hunter T, Drebin JA, O'Dwyer PJ, Liddle C, Tuveson DA, Downes M, Evans RM. Vitamin D receptor-mediated stromal reprogramming suppresses pancreatitis and enhances pancreatic cancer therapy. Cell. 2014 Sep 25;159(1):80-93. doi: 10.1016/j.cell.2014.08.007.
• Blauer M, Sand J, Laukkarinen J. Physiological and clinically attainable concentrations of 1,25-dihydroxyvitamin D3 suppress proliferation and extracellular matrix protein expression in mouse pancreatic stellate cells. Pancreatology. 2015 Jul-Aug;15(4):366-71. doi: 10.1016/j.pan.2015.05.044. Epub 2015 May 14.
• Hathcock JN, Shao A, Vieth R, Heaney R. Risk assessment for vitamin D. Am J Clin Nutr. 2007 Jan;85(1):6-18. doi: 10.1093/ajcn/85.1.6.
• Steffensen LH, Jorgensen L, Straume B, Mellgren SI, Kampman MT. Can vitamin D supplementation prevent bone loss in persons with MS? A placebo-controlled trial. J Neurol. 2011 Sep;258(9):1624-31. doi: 10.1007/s00415-011-5980-6. Epub 2011 Mar 13.
• Stallings VA, Schall JI, Hediger ML, Zemel BS, Tuluc F, Dougherty KA, Samuel JL, Rutstein RM. High-dose vitamin D3 supplementation in children and young adults with HIV: a randomized, placebo-controlled trial. Pediatr Infect Dis J. 2015 Feb;34(2):e32-40. doi: 10.1097/INF.0000000000000483.

Helpful Links

• Scientific Opinion on the Tolerable Upper Intake Level of vitamin D

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2016
• Primary Completion (Anticipated): August 1, 2024
• Study Completion (Anticipated): January 1, 2027

Study Registration Dates

• First Submitted: September 23, 2016
• First Submitted That Met QC Criteria: November 14, 2016
• First Posted (Estimate): November 17, 2016

Study Record Updates

• Last Update Posted (Actual): November 30, 2022
• Last Update Submitted That Met QC Criteria: November 29, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: pancreatitis; chronic pancreatitis; vitamin d; Pancreatic stellate cell; rct
• Additional Relevant MeSH Terms: Digestive System Diseases; Pancreatic Diseases; Pancreatitis; Pancreatitis, Chronic; Physiological Effects of Drugs; Micronutrients; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Vitamins; Ergocalciferols
• Other Study ID Numbers: R16004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: The data will be written into an article, which shall be displayed in a national and international forum.
• IPD Sharing Supporting Information Type: Study Protocol; Informed Consent Form (ICF)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No