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

NCT02706236 | Withdrawn Phase 2 DMC

• 1 other identifier: D16084
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Pancreatitis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Quality of life

  Pancreatic Quality of Life Instrument (PANQOLI) assessment at weeks 0, 4, 6 and 10

• Change in Narcotic Use

  0, 4, 6 and 10 weeks of treatment

Study Arms (2)

Intervention Arm

ACTIVE COMPARATOR

Pancreatic enzyme replacement (Pancrelipase) with meals and snacks daily, for 4 weeks.

Drug: Pancrelipase

Placebo Arm

PLACEBO COMPARATOR

Lactose placebo tablets with meals and snacks, for 4 weeks.

Drug: placebo

Interventions

Pancrelipase DRUG

Oral Pancrelipase, 720,000 units spread throughout the day with meals and snacks, taken daily PO for 4 weeks

Intervention Arm

placebo DRUG

Placebo will consist of lactose, spread throughout the day with meals and snacks, taken daily PO for 4 weeks

Placebo Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Pregnancy
• Lactation
• Active acute pancreatitis or an episode of acute pancreatitis within 2 months of presentation for evaluation
• Pancreatic cancer

Sponsors & Collaborators

• Dartmouth-Hitchcock Medical Center: lead

Study Sites (1)

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Related Publications (28)

• Drewes AM, Krarup AL, Detlefsen S, Malmstrom 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.

  PMID: 18566105 BACKGROUND

• 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.

  PMID: 21676159 BACKGROUND

• 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. doi: 10.1016/s0016-5107(94)70260-8.

  PMID: 7988825 BACKGROUND

• 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. doi: 10.1097/00006676-199507000-00008.

  PMID: 7667246 BACKGROUND

• 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.

  PMID: 21683160 BACKGROUND

• 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. No abstract available.

  PMID: 6104938 BACKGROUND

• 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. doi: 10.1023/a:1026607703352.

  PMID: 10389680 BACKGROUND

• 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. doi: 10.3181/00379727-140-36384. No abstract available.

  PMID: 5033119 BACKGROUND

• Ihse I, Lilja P, Lundquist I. Feedback regulation of pancreatic enzyme secretion by intestinal trypsin in man. Digestion. 1977;15(4):303-8. doi: 10.1159/000198016.

  PMID: 863133 BACKGROUND

• 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. doi: 10.1172/JCI112534.

  PMID: 3711342 BACKGROUND

• 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.

  PMID: 3973464 BACKGROUND

• 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.

  PMID: 9362186 BACKGROUND

• 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

  BACKGROUND

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

  PMID: 6202586 BACKGROUND

• Isaksson G, Ihse I. Pain reduction by an oral pancreatic enzyme preparation in chronic pancreatitis. Dig Dis Sci. 1983 Feb;28(2):97-102. doi: 10.1007/BF01315137.

  PMID: 6825540 BACKGROUND

• 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.

  PMID: 19243769 BACKGROUND

• 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.

  PMID: 22195253 BACKGROUND

• 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

  BACKGROUND

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

  PMID: 6689654 BACKGROUND

• 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. doi: 10.1152/ajpgi.1986.250.2.G252.

  PMID: 3953805 BACKGROUND

• 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. doi: 10.1159/000128145.

  PMID: 6167444 BACKGROUND

• Mossner 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. doi: 10.1159/000200971.

  PMID: 1289173 BACKGROUND

• 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.

  PMID: 19451744 BACKGROUND

• 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.

  PMID: 19035969 BACKGROUND

• Gullo L, Barbara L, Labo G. Effect of cessation of alcohol use on the course of pancreatic dysfunction in alcoholic pancreatitis. Gastroenterology. 1988 Oct;95(4):1063-8. doi: 10.1016/0016-5085(88)90184-9.

  PMID: 3410221 BACKGROUND

• Midanik L. The validity of self-reported alcohol consumption and alcohol problems: a literature review. Br J Addict. 1982 Dec;77(4):357-82. doi: 10.1111/j.1360-0443.1982.tb02469.x. No abstract available.

  PMID: 6762224 BACKGROUND

• 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. doi: 10.1016/j.suc.2007.08.014.

  PMID: 18053843 BACKGROUND

• 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. doi: 10.1016/s0016-5107(98)70123-3.

  PMID: 9684659 BACKGROUND

MeSH Terms

Conditions

Pancreatitis

Interventions

Pancrelipase

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Lipase; Carboxylic Ester Hydrolases; Esterases; Hydrolases; Enzymes; Enzymes and Coenzymes; Pancreatic Extracts; Tissue Extracts; Complex Mixtures

Study Officials

• Timothy B Gardner, MD

  Dartmouth-Hitchcock Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: February 27, 2016
• First Posted: March 11, 2016
• Study Start: April 1, 2016
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2018
• Last Updated: February 27, 2018

Record last verified: 2018-02

Data Sharing

• IPD Sharing: Will share

Locations

US (1)