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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT00156403
First received: September 8, 2005
Last updated: December 13, 2007
Last verified: December 2007
  Purpose

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.


Condition Intervention Phase
Pancreatitis
Drug: amlodipine (drug)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Hereditary Pancreatitis Amlodipine Trial(H-PAT): A Pilot Study

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

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

Secondary Outcome Measures:
  • 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)

Estimated Enrollment: 8
Study Start Date: August 2005
Study Completion Date: December 2005
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.

  Eligibility

Ages Eligible for Study:   6 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00156403

Locations
United States, Pennsylvania
General Clinical Research Center, University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
University of Pittsburgh
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
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00156403     History of Changes
Other Study ID Numbers: 0505070, CReFF Award, GCRC U Pittsburgh, National Pancreas Foundation
Study First Received: September 8, 2005
Last Updated: December 13, 2007
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Pittsburgh:
pancreatitis, hereditary
trypsinogen, cationic
pilot study

Additional relevant MeSH terms:
Pancreatitis
Pancreatitis, Chronic
Pancreatic Diseases
Digestive System Diseases
Calcium Channel Blockers
Amlodipine
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Antihypertensive Agents
Vasodilator Agents

ClinicalTrials.gov processed this record on August 28, 2014