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

December 13, 2007 updated by: University of Pittsburgh

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

The study has three main purposes: to determine whether the use of amlodipine appears to be safe in this patient population, to determine how frequently and how best to follow subjects while they are taking the medication, and to determine whether there are any indications of potential benefits to the medication (whether by decreased symptoms frequency/ severity or by inflammatory cytokines analysis).

A subsequent larger study would be designed based on the above results.

Study Type

Interventional

Enrollment

8

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • General Clinical Research Center, University of Pittsburgh

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • mutation in cationic trypsinogen (PRSS1)gene
  • age 6 years and above
  • able to comply with study terms: taking daily oral medication, taking daily blood pressure, filling in daily symptoms diary, coming to all follow-up visits
  • having some symptoms of pain from pancreas

Exclusion Criteria:

  • combination of mutations in the 2 other loci associated with pancreatitis: Cystic fibrosis transmembrane regulator and serine protease inhibitor Kazal type 1 (having mutations in both genes)
  • pancreatic insufficiency (exocrine and endocrine)
  • already being on an antihypertensive medication
  • contraindication to taking amlodipine (allergic reaction, severe renal failure (creatinine > 3 mg/dL; hepatic dysfunction signified by INR > 1.5)
  • pregnancy or breastfeeding
  • systemic disease that the investigators feel would place patient at undue risk of being placed on amlodipine
  • newly-started (within past 3 months) pancreatic enzymes, acid blocking medication, antioxidants, or oral contraceptive medication

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Pittsburgh

Collaborators

National Center for Research Resources (NCRR)

Investigators

  • Study Director: David C Whitcomb, MD, PhD, Chief, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh and University of Pittsburgh Medical Center, M2, C-Wing, Presbyterian Hospital, 200 Lothrop Street, Pittsburgh PA 15213

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2005

Study Completion (Actual)

December 1, 2005

Study Registration Dates

First Submitted

September 8, 2005

First Submitted That Met QC Criteria

September 8, 2005

First Posted (Estimate)

September 12, 2005

Study Record Updates

Last Update Posted (Estimate)

December 17, 2007

Last Update Submitted That Met QC Criteria

December 13, 2007

Last Verified

December 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0505070
  • CReFF Award, GCRC U Pittsburgh
  • National Pancreas Foundation

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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