Clinical Trial: A Pilot Study of Use of Calcium Channel Blocker to Decrease Inflammation and Pain in Hereditary Pancreatitis

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Hereditary Pancreatitis Amlodipine Trial(H-PAT): A Pilot Study

Brief Summary: This pilot study is a feasibility, safety, and preliminary benefits study to look at whether giving the calcium channel blocker amlodipine to people with hereditary pancreatitis as a prophylactic measure can reduce the inflammatory process in the pancreas.

Detailed Summary:

Hereditary Pancreatitis is a rare, autosomal dominantly inherited condition causing mutations in the cationic trypsinogen gene. These mutations lead to excessive activation of trypsinogen within the pancreatic acinar cells and subsequent pancreatic inflammation. Clinically, this may be observed as recurrent acute pancreatitis, chronic pancreatitis, and eventual complications of exocrine and endocrine pancreatic insufficiencies and pancreatic adenocarcinoma. Currently, there are no specific treatment or prophylactic measures for this condition.

Calcium is the physiologic switch to activate trypsinogen. It has recently been found that the mutation sites affect how tightly calcium binds to trypsinogen, with mutations leading to excessive calcium binding and subsequent excessive trypsinogen activation. This study is to obtain baseline data on whether the prophylactic use of a long-acting calcium channel blocker, amlodipine, would lead to decrease in the inappropriate activation of trypsinogen, and thereby decrease the subsequent pancreatic inflammation.

Up to 15 subjects, aged 6 years and above, with mutations in the cationic trypsinogen gene (PRSS1) will be recruited and undergo a 16-week trial. This will include a one-month baseline symptoms assessment (daily symptoms diary) and blood pressure measurements (with an automated home blood pressure monitor). Subsequently, subjects will be placed on between 2.5 - 10 mg amlodipine po qd (with a weaning up and weaning down phase) for approximately 10 weeks. They will continue to fill out daily symptoms diary, blood pressure measurements (to ensure there are no decreases), fill out periodic quality of life questionnaires, and undergo periodic blood testing for routine biochemistry as well as more specialized testing for proteomics and other inflammatory cytokines analysis.

Sponsor: University of Pittsburgh

Current Primary Outcome:

  • safety of amlodipine: side effects, biochemistry, BP
  • efficacy: symptoms diary, SF-36, cytokines analysis


Original Primary Outcome: Same as current

Current Secondary Outcome: feasibility: ease of obtaining patient symptoms information, whether subjects need to be followed up as frequently as designated in this pilot, whether doing regular laboratory tests changed management in any way (i.e. whether it was necessary)

Original Secondary Outcome: Same as current

Information By: University of Pittsburgh

Dates:
Date Received: September 8, 2005
Date Started: August 2005
Date Completion:
Last Updated: December 13, 2007
Last Verified: December 2007