Enzyme Suppletion in Exocrine Pancreatic Dysfunction (SAPES)

Enzyme Substitution in Exocrine Pancreatic Insufficiency; Self Administration Against a Fixed Dose Regimen

Treatment of exocrine insufficiency (EPI) consists of pancreatic enzyme replacement according to the fat intake. Prescribing a sufficient dose of pancreatic enzymes is mandatory for the treatment to be effective. In addition, consultation of a specialized dietician is pivotal to educate patients about the proper use of pancreatic enzymes. However, based on a recent prospective survey in the Netherlands amongst chronic pancreatitis patients, it seems that enzymes are underused and a dietician is seldom consulted. The aim of this study is to assess if there is a difference in efficacy of pancreatic enzymes in a self-dosage regimen after extensive patient-education in comparison to the standard treatment for patients with EPI.

Study Overview

• Status: Completed
• Conditions: Chronic Pancreatitis; Exocrine Pancreatic Insufficiency
• Intervention / Treatment: Drug: Panzytrat 25.000 FIP-E units of Lipase

Detailed Description

This is a prospective, open, comparative study with a linear design with two sequential phases (observatory, then patient-monitored).

The research population consists of patients who are treated with pancreatic enzymes (< 6 capsules p/d containing 25,000 units of lipase) for exocrine insufficiency caused by chronic pancreatitis.

After inclusion, patients will discontinue taking pancreatic enzymes during one week (wash-out period). The last four days of this week, a fecal fat balance test will be performed to quantify the fecal fat loss without enzyme correction. If the fecal fat excretion is less than 15%, this is considered normal and therefore the patient will be excluded from the study. Subsequently, the next three weeks of the trial the patient will restart using the same dose of pancreatic enzymes the way it was prescribed before inclusion. The last four days of the fourth week, a fecal fat balance test will be repeated to quantify the fecal fat loss with enzyme correction. After this test the intervention takes place, consisting of a standardised education of the patient by a dietician. In the second phase of four weeks, patients are stimulated to use this information to self-dose the amount of pancreatic enzymes according to the fat content of their diet. In the last week of the study a fecal fat balance test will be repeated.

The primary endpoint is the fecal fat excretion. Secondary endpoints are the change in enzyme dose after intervention, improvement of complaints (e.g. steatorrhoea related complaints, abdominal cramps, abdominal pain), change in dietary habits, patient satisfaction, quality of life, evaluation of the nutritional status, and the occurrence of side effects.

Because the maximum amount of 16 capsules of pancreatic enzymes a day according to the standard guidelines will not be exceeded in this trial, no risks are foreseen. The anticipated benefit of the study is that patients will be treated more effectively for their EPI. The burden of this trial for patients is the repeated fecal fat balance test.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 4

Contacts and Locations

Study Locations

• Netherlands
  • Zuid-Holland
    • Rotterdam, Zuid-Holland, Netherlands, 3000 WB
      • Erasmus Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 88 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age ≥ 18 years.
• EPI caused by CP.
• Treated with enzyme therapy (≤ 6 capsules of 25.000 FIP-E units of lipase per day).
• Fecal elastase < 0.200 mg/g
• fecal fat-absorption < 85% without using enzymes.

Exclusion Criteria:

• Subjects who are unwilling or unable to understand and participate in the study and/or sign the informed consent.
• Any known gastro-intestinal disease or major gastrointestinal or pancreatic surgery that could potentially affect the intestinal absorption or metabolism of fat
• Gastroparesis of any aetiology
• Hypersensitivity to pork protein
• Acute pancreatitis
• Limited life-expectancy of ≤ 6 months
• Malignancy of the pancreas
• Pregnancy/lactation

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Panzytrat fixed dose vs. self-dosing; In Phase I (week 1-4) patients will use the fixed amount of lipase as was prescribed by their treating physician. Phase II (week 5-9) patients will start the self-dosage regimen with pancreatic enzymes (without exceeding the maximum amount of 16 capsules per day). They are properly educated by the researcher and dietician how to adjust the amount of pancreatic enzymes to the fat intake in their diet.

Drug: Panzytrat 25.000 FIP-E units of Lipase; patients will experiment with Panzytrat (containing 25.000 units of lipase) to a maximum of 16 capsules a day according to general guidelines.; Other Names: Pancreatine of porcine-origin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fecal Fat percentage	difference in efficacy measured by the fecal fat content during treatment with pancreatic enzymes in a self-dosage regimen after extensive patient-education in comparison to the standard treatment for patients with EPI due to chronic pancreatitis	week 1, 5 and 9

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
enzyme dose	Change in enzyme dose	On a weekly base during 9 weeks
Improvement of steatorrhea-related complaints	Improvement of complaints (e.g. steatorrhoea, abdominal cramps, abdominal pain).	On a weekly base during 9 weeks
Change in dietary habits	Change in dietary habits by means of a food diary	Week 1, 5 and 9
Patient satisfaction	Patient satisfaction by means of a SF36 questionnaire	Week 4 and 9
Quality of life	Quality of life by means of a SF36 questionnaire	week 4 and 9
Evaluation of the nutritional status	Evaluation of the nutritional status in the blood and calculating the Body Mass Index (BMI)	week 5 and 9

Collaborators and Investigators

• Sponsor: Foundation for Liver Research
• Collaborators: Axcan Pharma
• Investigators: Principal Investigator: Marco Bruno, MD, PhD, Department of Gastroeneterology and Hepatology, Erasmus University Medical Center

Publications and helpful links

General Publications

• Ramo OJ, Puolakkainen PA, Seppala K, Schroder TM. Self-administration of enzyme substitution in the treatment of exocrine pancreatic insufficiency. Scand J Gastroenterol. 1989 Aug;24(6):688-92. doi: 10.3109/00365528909093110.
• Czako L, Takacs T, Lonovics J, Lakner L, Dobronte Z, Pronai L, Tulassay Z. [Quality of life in the course of enzyme replacement therapy for chronic pancreatitis]. Orv Hetil. 2002 Jun 23;143(25):1521-7. Hungarian.
• Delhaye M, Meuris S, Gohimont AC, Buedts K, Cremer M. Comparative evaluation of a high lipase pancreatic enzyme preparation and a standard pancreatic supplement for treating exocrine pancreatic insufficiency in chronic pancreatitis. Eur J Gastroenterol Hepatol. 1996 Jul;8(7):699-703.
• Bruno MJ, Tytgat GN. [4 patients with painless diarrhea and weight loss]. Ned Tijdschr Geneeskd. 1994 Dec 17;138(51):2529-33. No abstract available. Dutch.

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Actual): February 1, 2013
• Study Completion (Actual): February 1, 2013

Study Registration Dates

• First Submitted: September 1, 2011
• First Submitted That Met QC Criteria: September 7, 2011
• First Posted (Estimate): September 8, 2011

Study Record Updates

• Last Update Posted (Estimate): March 11, 2015
• Last Update Submitted That Met QC Criteria: March 10, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: Chronic pancreatitis; Exocrine insufficiency; Pancreatic enzyme replacement therapy; Self-administration
• Additional Relevant MeSH Terms: Digestive System Diseases; Pancreatic Diseases; Pancreatitis; Pancreatitis, Chronic; Exocrine Pancreatic Insufficiency; Gastrointestinal Agents; Pancreatin
• Other Study ID Numbers: SAPES