Trial of Pancreatic Enzyme Supplements (Pancrelipase) for Treating Pain in Patients With Chronic Pancreatitis

Pancreatitis Clinical Trial

Official title:

A Single-Center Prospective Randomized Placebo Controlled Trial of Pancreatic Enzyme Supplements (Pancrelipase) for Treating Pain in Patients With Chronic Pancreatitis

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02706236
• Other study ID #: D16084
• Status: Withdrawn
• Phase: Phase 2
• First received: February 27, 2016
• Last updated: February 25, 2018
• Start date: April 2016
• Est. completion date: December 2018

Study information

• Verified date: February 2018
• Source: Dartmouth-Hitchcock Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study purpose is to characterize the effect of pancreatic enzyme supplementation on chronic pancreatitis type pain.

Description:

Study Type: Interventional, randomized, double-blind, placebo-controlled, crossover design, efficacy study Intervention arm: Pancreatic enzyme replacement (Pancrelipase) with meals and snacks daily, for 4 weeks.

Placebo arm: Lactose placebo tablets with meals and snacks, for 4 weeks. Washout Phase: Weeks 4 to 6, there will be cessation of placebo or Pancrelipase use.

Crossover Phase: Weeks 6 to 10, initial placebo arm receives Pancrelipase, Pancrelipase arm receives placebo

Surveys - Izbicki score and PANQOLI assessment occur at Week 0, 4, 6, and 10. Narcotic and non-narcotic usage will also be noted at these intervals. Patient will also report the tobacco and alcohol use.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 2018
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Diagnosis of chronic pancreatitis based on chronic pancreatitis-type pain > 6 months leading to impaired quality of life AND at least 1 of the following (27):

• Confirmed diagnosis of hereditary pancreatitis (PRSS1 gene mutation)

• History of recurrent acute pancreatitis (>1 documented episode of characteristic abdominal pain associated with diagnostic imaging and/or elevated serum amylase or lipase > 3 times upper limit of normal).

• Pancreatic calcifications on CT scan

• At least 2 of the following:

• Endoscopic Ultrasound (EUS) with = or > 4 criteria for chronic pancreatitis (hyperechoic foci, strands, or ducts, lobulation, irregular duct margin, visible side
• branches, calcifications, cysts, ductal dilatation) (28)

• Ductal (changes in side branch morphology) or parenchymal (loss of T1 signal intensity) abnormalities on secretin enhanced Magnetic resonance cholangiopancreatography (MRCP)

• Abnormal endoscopic pancreatic secretory function tests (HCO3 <= 75mmol/L at 30 or 45 minutes or <= 80mmol/L at 1 hour

• Subjects are capable of informed consent

Exclusion Criteria:

• Pregnancy

• Lactation

• Active acute pancreatitis or an episode of acute pancreatitis within 2 months of presentation for evaluation

• Pancreatic cancer

Related Conditions & MeSH terms

• Pancreatitis
• Pancreatitis, Chronic

Intervention

Drug:
• Pancrelipase
Oral Pancrelipase, 720,000 units spread throughout the day with meals and snacks, taken daily PO for 4 weeks
• placebo
Placebo will consist of lactose, spread throughout the day with meals and snacks, taken daily PO for 4 weeks

Locations

Country	Name	City	State
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire

Sponsors (1)

Lead Sponsor	Collaborator
Dartmouth-Hitchcock Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (28)

Bellin MD, Freeman ML, Schwarzenberg SJ, Dunn TB, Beilman GJ, Vickers SM, Chinnakotla S, Balamurugan AN, Hering BJ, Radosevich DM, Moran A, Sutherland DE. Quality of life improves for pediatric patients after total pancreatectomy and islet autotransplant for chronic pancreatitis. Clin Gastroenterol Hepatol. 2011 Sep;9(9):793-9. doi: 10.1016/j.cgh.2011.04.024. Epub 2011 May 5. — View Citation

Bloechle C, Izbicki JR, Knoefel WT, Kuechler T, Broelsch CE. Quality of life in chronic pancreatitis--results after duodenum-preserving resection of the head of the pancreas. Pancreas. 1995 Jul;11(1):77-85. — View Citation

Blondet JJ, Carlson AM, Kobayashi T, Jie T, Bellin M, Hering BJ, Freeman ML, Beilman GJ, Sutherland DE. The role of total pancreatectomy and islet autotransplantation for chronic pancreatitis. Surg Clin North Am. 2007 Dec;87(6):1477-501, x. Review. — View Citation

Brown A, Hughes M, Tenner S, Banks PA. Does pancreatic enzyme supplementation reduce pain in patients with chronic pancreatitis: a meta-analysis. Am J Gastroenterol. 1997 Nov;92(11):2032-5. — View Citation

Catalano MF, Sahai A, Levy M, Romagnuolo J, Wiersema M, Brugge W, Freeman M, Yamao K, Canto M, Hernandez LV. EUS-based criteria for the diagnosis of chronic pancreatitis: the Rosemont classification. Gastrointest Endosc. 2009 Jun;69(7):1251-61. doi: 10.1016/j.gie.2008.07.043. Epub 2009 Feb 24. — View Citation

Drewes AM, Krarup AL, Detlefsen S, Malmstrøm ML, Dimcevski G, Funch-Jensen P. Pain in chronic pancreatitis: the role of neuropathic pain mechanisms. Gut. 2008 Nov;57(11):1616-27. doi: 10.1136/gut.2007.146621. Epub 2008 Jun 19. Review. — View Citation

Green GM, Lyman RL. Feedback regulation of pancreatic enzyme secretion as a mechanism for trypsin inhibitor-induced hypersecretion in rats. Proc Soc Exp Biol Med. 1972 May;140(1):6-12. — View Citation

Gullo L, Barbara L, Labò G. Effect of cessation of alcohol use on the course of pancreatic dysfunction in alcoholic pancreatitis. Gastroenterology. 1988 Oct;95(4):1063-8. — View Citation

Ihse I, Lilja P, Lundquist I. Feedback regulation of pancreatic enzyme secretion by intestinal trypsin in man. Digestion. 1977;15(4):303-8. — View Citation

Isaksson G, Ihse I. Pain reduction by an oral pancreatic enzyme preparation in chronic pancreatitis. Dig Dis Sci. 1983 Feb;28(2):97-102. — View Citation

Kozarek RA, Ball TJ, Patterson DJ, Brandabur JJ, Traverso LW, Raltz S. Endoscopic pancreatic duct sphincterotomy: indications, technique, and analysis of results. Gastrointest Endosc. 1994 Sep-Oct;40(5):592-8. — View Citation

Lilja P. Effects of intraduodenal amylase, lipase, trypsin, and bile on pancreatic enzyme secretion in the rat. Eur Surg Res. 1980;12(6):383-91. — View Citation

Louie DS, May D, Miller P, Owyang C. Cholecystokinin mediates feedback regulation of pancreatic enzyme secretion in rats. Am J Physiol. 1986 Feb;250(2 Pt 1):G252-9. — View Citation

Midanik L. The validity of self-reported alcohol consumption and alcohol problems: a literature review. Br J Addict. 1982 Dec;77(4):357-82. Review. — View Citation

Miyasaka K, Green GM. Effect of partial exclusion of pancreatic juice on rat basal pancreatic secretion. Gastroenterology. 1984 Jan;86(1):114-9. — View Citation

Mössner J, Secknus R, Meyer J, Niederau C, Adler G. Treatment of pain with pancreatic extracts in chronic pancreatitis: results of a prospective placebo-controlled multicenter trial. Digestion. 1992;53(1-2):54-66. — View Citation

Owyang C, Louie DS, Tatum D. Feedback regulation of pancreatic enzyme secretion. Suppression of cholecystokinin release by trypsin. J Clin Invest. 1986 Jun;77(6):2042-7. — View Citation

Pancreatic Enzyme Supplementation for Treatment of Pain in Adult Patients with Chronic Pancreatitis: a Meta-Analysis and Systematic Review [abstract]. Gardner TB, Michalak D, Harrington MW, et al

Puylaert M, Kapural L, Van Zundert J, Peek D, Lataster A, Mekhail N, van Kleef M, Keulemans YC. 26. Pain in chronic pancreatitis. Pain Pract. 2011 Sep-Oct;11(5):492-505. doi: 10.1111/j.1533-2500.2011.00474.x. Epub 2011 Jun 16. Review. — View Citation

Radnay PA, Brodman E, Mankikar D, Duncalf D. The effect of equi-analgesic doses of fentanyl, morphine, meperidine and pentazocine on common bile duct pressure. Anaesthesist. 1980 Jan;29(1):26-9. — View Citation

Sahai AV, Zimmerman M, Aabakken L, Tarnasky PR, Cunningham JT, van Velse A, Hawes RH, Hoffman BJ. Prospective assessment of the ability of endoscopic ultrasound to diagnose, exclude, or establish the severity of chronic pancreatitis found by endoscopic retrograde cholangiopancreatography. Gastrointest Endosc. 1998 Jul;48(1):18-25. — View Citation

Slaff J, Jacobson D, Tillman CR, Curington C, Toskes P. Protease-specific suppression of pancreatic exocrine secretion. Gastroenterology. 1984 Jul;87(1):44-52. — View Citation

Slaff JI, Wolfe MM, Toskes PP. Elevated fasting cholecystokinin levels in pancreatic exocrine impairment: evidence to support feedback regulation. J Lab Clin Med. 1985 Mar;105(3):282-5. — View Citation

US Food and Drug Administration. FDA Approves Pancreatic Enzyme Replacement Product for Marketing in United States. Creon designed to help those with cystic fibrosis, others with exocrine pancreatic insufficiency. May 7th, 2009. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm149579.htm

Waljee AK, Dimagno MJ, Wu BU, Schoenfeld PS, Conwell DL. Systematic review: pancreatic enzyme treatment of malabsorption associated with chronic pancreatitis. Aliment Pharmacol Ther. 2009 Feb 1;29(3):235-46. doi: 10.1111/j.1365-2036.2008.03885.x. Epub 2008 Nov 8. Review. — View Citation

Wilder-Smith CH, Hill L, Osler W, O'Keefe S. Effect of tramadol and morphine on pain and gastrointestinal motor function in patients with chronic pancreatitis. Dig Dis Sci. 1999 Jun;44(6):1107-16. — View Citation

Winstead NS, Wilcox CM. Clinical trials of pancreatic enzyme replacement for painful chronic pancreatitis--a review. Pancreatology. 2009;9(4):344-50. doi: 10.1159/000212086. Epub 2009 May 18. Review. — View Citation

Zubarik R, Ganguly E. The rosemont criteria can predict the pain response to pancreatic enzyme supplementation in patients with suspected chronic pancreatitis undergoing endoscopic ultrasoun. Gut Liver. 2011 Dec;5(4):521-6. doi: 10.5009/gnl.2011.5.4.521. Epub 2011 Nov 21. — View Citation

* Note: There are 28 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in pain scores based on Izbicki self-assessment score	Difference in pain scores based on Izbicki self-assessment will be evaluated to determine if pancrelipase improves pain symptoms in patients with chronic pancreatitis	Measured at weeks 0,4,6 and 10
Secondary	Quality of life	Difference in quality of live evaluated on PANQOLI assessment	Pancreatic Quality of Life Instrument (PANQOLI) assessment at weeks 0, 4, 6 and 10
Secondary	Change in Narcotic Use	Difference in narcotic and non-narcotic use at 0, 4, 6 and 10 weeks of treatment as measured by morphine equivalents	0, 4, 6 and 10 weeks of treatment