Hereditary pancreatitis amlodipine trial: a pilot study of a calcium-channel blocker in hereditary pancreatitis.
OBJECTIVE
Hereditary pancreatitis (HP) is a form of recurrent acute pancreatitis (AP) mediated by mutations in cationic trypsinogen (PRSS1). Mutations cluster in the calcium-associated regulator regions of PRSS1. In rats, calcium-channel blockers (CCB) prevent hyperstimulation-associated AP. Because of the potential importance of hyperstimulation in triggering episodes of AP in HP, we designed a pilot study to evaluate the safety and potential benefit of CCB use in HP.


METHODS
Subjects 6 years or older had a PRSS1 mutation, recurrent AP, and pain. Total study duration was 16 weeks. Amlodipine was given during weeks 0 to 11. Dose (2.5, 5, or 10 mg) was based on weight (range, 0.08-0.17 mg x kg(-1) x d(-1)). Subjects filled a daily diary including pain (0-10 scale) and blood pressure reading. Clinical assessments occurred at weeks -4, 0, 1, 2, 6, 10, 11, and 12. Subjects filled a Medical Outcomes Study Short-Form Survey version 2 (SF-10 for children <14 years old) at weeks -4, 0, 6, and 10. Data were compared for weeks -4 to 0 and 6 to 10.


RESULTS
Nine subjects signed informed consent (4 males; 12-52 years old). Four were excluded during the screening phase. Drug was discontinued in one due to development of unilateral lower-extremity numbness. Four subjects (12-31 years old) completed the study. Mean blood pressure, laboratory tests, physical findings, and daily pain scores did not clinically significantly differ before and during drug therapy, but all reported reduced symptoms. Three reduced analgesic use. Three had improved scores on the Medical Outcomes Study Short-Form Survey version 2.


CONCLUSIONS
Amlodipine is generally safe in subjects with HP and does not increase pain or episodes of AP. Further research into the mechanism of CCB on pancreatitis would be important to provide a pathophysiologic basis to support further trials in HP.
Morinville
Véronique D
VD
Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Lowe
Mark E
ME
Elinoff
Beth D
BD
Whitcomb
David C
DC
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D017311:Amlodipine / Q000009:adverse effects / Q000627:therapeutic use*; D000700:Analgesics / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D005240:Feasibility Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010146:Pain / Q000209:etiology / Q000517:prevention & control*; D010147:Pain Measurement; D010195:Pancreatitis / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D010352:Patient Dropouts; D010865:Pilot Projects; D011446:Prospective Studies; D011788:Quality of Life; D012008:Recurrence; D012307:Risk Factors; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome; D014357:Trypsin; D014362:Trypsinogen / Q000235:genetics
D000700:Analgesics; D002121:Calcium Channel Blockers; D017311:Amlodipine; D014362:Trypsinogen; C489303:PRSS1 protein, human; D014357:Trypsin