Symptomatic effect of pancreatic enzyme therapy in patients with chronic pancreatitis. Therapy of pancreatogenic steatorrhoea: does acid protection of pancreatic enzymes offer any advantage? Pain reduction by an oral pancreatic enzyme preparation in chronic pancreatitis. Comparative evaluation of a high lipase pancreatic enzyme preparation and a standard pancreatic supplement for treating exocrine pancreatic insufficiency in chronic pancreatitis. Omeprazole, a proton pump inhibitor, improves residual steatorrhoea in cystic fibrosis patients treated with high dose pancreatic enzymes. Treatment of pain with pancreatic extracts in chronic pancreatitis: results of a prospective placebo-controlled multicenter trial. The effects of oral pancreatic enzymes (Creon 10 capsule) on steatorrhea: a multicenter, placebo-controlled, parallel group trial in subjects with chronic pancreatitis. The exacerbation of pancreatic endocrine dysfunction by potent pancreatic exocrine supplements in patients with chronic pancreatitis. Effect of the administration schedule on the therapeutic efficacy of oral pancreatic enzyme supplements in patients with exocrine pancreatic insufficiency: a randomized, three-way crossover study.
The symptomatic effect of pancreatic enzyme substitution therapy was examined in a 4-week double-blind crossover study. Twenty patients, 11 with and 9 without steatorrhoea, were examined. Pancreatic steatorrhoea was reduced from a median of 24 g/day to 10 g/day by the enzyme therapy (P less than 0.01). No significant pain reduction was found in either of the two groups, although there was a tendency to reduction in pain and analgetic consumption in the patients with steatorrhoea when treated with pancreatic enzymes. It is concluded that pancreatic steatorrhoea is still the only indication for pancreatic enzyme therapy. Pancreatic enzyme replacement may fail to achieve a beneficial effect because of enzyme inactivation by gastric acid. In this controlled randomized study, 8 hospitalized patients with severe exocrine pancreatic insufficiency and considerable steatorrhoea (greater than 15 g faecal fat/day) were treated with a conventional pancreatic enzyme preparation (Pankreon 700; 3 X 3 dragees daily), with (300 mg) and without cimetidine before meals, and with a new pH-sensitive enzyme preparation (Kreon; 3 X 6 capsules daily) comprising acid-protected granules. Both conventional enzyme replacement plus cimetidine, and acid-protected pancreatin were significantly (p less than 0.05) more effective than conventional enzyme therapy alone. Since both regimens are equally potent in overcoming gastric acid-induced enzyme inactivation, it is concluded that therapy with acid-protected pancreatin may simplify and improve treatment of exocrine pancreatic insufficiency in the presence of gastric hyper- or normo-acidity. In a double-blind study on 19 patients with the diagnosis of chronic pancreatitis, the effects of treatment with a granulated pancreatic enzyme preparation (Pankreon) were compared with those of placebo administration. One week of treatment with each preparation was preceded by one week without any medication. The patients kept daily records of their symptoms, plotting the severity of pain on an analog scale. Weekly assessments of the mean pain level were also made by an examiner questioning the patients. Recordings of body weights and pancreas and liver laboratory tests were done weekly. Fifteen of 19 patients noted less pain during the week of treatment with pancreatic enzymes as compared to that of placebo treatment (P less than 0.05). The average reduction of pain, as calculated for all patients, was 30% as evaluated by both patients (P less than 0.01) and the examiner (P less than 0.05). No differences were found in other parameters examined. A possible explanation of the findings could be an effect on the intraductal pressure by intraluminal trypsin. To compare the efficacy and safety of two enzyme-containing preparations, Pancrease HL (Cilag) containing 25,000 units of lipase per capsule and Creon (Triosol) with 8000 units of lipase per capsule, in patients with chronic pancreatitis and exocrine insufficiency.
                The study is a monocentric open crossover prospective study including 25 patients entered from March 1993 to May 1994.
                Chronic pancreatitis was alcohol-related in 23 patients, previous surgery was performed in 9, 16 had diabetes and all had steatorrhoea (fat balance > 10g/24h).
                Patients were investigated during four periods of 2 weeks, each one corresponding to a new treatment regimen: Pancrease HL, 3 capsules/day or Creon, 9 capsules/day, with or without omeprazole 20 mg/day. Stools were collected on the last 3 days at the end of each period when the patients were on a standard diet with a fixed daily intake of 100 g fat/day.
                Faecal fat, protein and energy excretion did not differ when both preparations were compared at roughly pharmaceutically equivalent doses. No significant improvement in fat and protein absorption was observed when omeprazole was taken with the pancreatic enzymes. However, omeprazole treatment was associated with a marked decrease in the fat-protein content ratio, suggesting an improvement in the fat digestive process but a decrease in the efficiency of protein digestion. Drug safety was comparable in the four groups of treatment.
                Pancrease HL with high lipase activity provides effective pancreatic enzyme replacement therapy in patients with chronic pancreatitis at an appreciably lower number of capsules per day than with standard preparations. Despite treatment with supra-physiological doses of pancreatic enzyme supplements, residual steatorrhoea is a common problem in patients with cystic fibrosis (CF) and pancreatic insufficiency. Strategies to enhance the activity of pancreatic enzymes include decreasing duodenal acidity. The aim of this study was to evaluate the effect of omeprazole (Losec), a proton-pump inhibitor, on fat absorption in CF patients with residual steatorrhoea despite high dose pancreatic enzyme supplements (> or =10,000 U lipase/kg per day). A random cross-over design was chosen. Fat digestion was evaluated with and without omeprazole by means of chemical fat measurements in 3-day stool collections together with 3-day weighed food records for calculation of fat absorption. The results of 15 patients (3 girls and 12 boys) with confirmed steatorrhoea during the control evaluation were analysed. Median age was 8.7 years (range 3.5-15.9 years). Median daily lipase intake was 13,500 U/kg per day (range 10,000-22,000 U/kg per day). During treatment with omeprazole, median faecal fat loss (g fat/day) decreased from 13 g (quartiles 11.5-16.5 g/day) to 5.5 g (quartiles 4.9-8.1 g/day) (P<0.01). The same improvement was noted when fat absorption was calculated: 87% (quartiles 81-89%) without versus 94% (quartiles 90-96%) with omeprazole (P<0.001).
                Omeprazole improves fat digestion and absorption in cystic fibrosis patients with residual faecal fat loss despite maximal pancreatic enzyme substitution. According to the theory of negative feedback regulation of pancreatic enzyme secretion by proteases, treatment with pancreatic extracts has been proposed to lower pain in chronic pancreatitis by decreasing pancreatic duct pressure. We conducted a prospective placebo-controlled double blind multicenter study to investigate the effect of porcine pancreatic extracts on pain in chronic pancreatitis. 47 patients with pain (41 males, 6 females) due to chronic pancreatitis documented by sonography, endoscopic retrograde cholangiopancreatography, and CT were included. Exclusion criteria were steatorrhea above 30 g/day, gastric or pancreatic resections in the history, and serum bilirubin above 1.5 mg/dl. Patients received pancreatic extracts (acid-protected microtablets; Panzytrat -20,000; 5 x 2 capsules/day; proteases/capsule 1,000 Pharmacopoea europaea units) for 14 days followed by treatment with placebo for another 14 days or vice versa. Pain (graded from 0 to 3) and concomitant use of analgesics (N-butylscopolaminiumbromide and tramadol) were recorded by diary. Physical examination and blood chemistry were done at day -1, 15 and 29. Quantitative stool fat was determined at days -2/-1, 13/14 and 27/28. 43 patients completed the studies. Pain improved in most patients irrespective of whether they started with placebo or verum. There was no significant difference between both treatment arms. We conclude that pancreatic extracts are not very efficient in lowering pain. Creon 10 Minimicrospheres is an enteric-coated, delayed-release pancrelipase preparation designed to deliver active pancreatic enzymes to the small intestine. The primary objective of this study was to compare the effect of Creon 10 with placebo in the control of steatorrhea in chronic pancreatitis patients. Secondary objectives included evaluation of stool parameters and global improvement of symptoms scales.
                The study was a randomized, double-blind, placebo-controlled, 2-week trial. After a placebo run-in ("washout") phase, the effect on coefficient of fat absorption (%), daily fat excretion before and after treatment, and stool frequency and consistency were assessed.
                In Creon 10-treated subjects, the change in mean coefficient of fat absorption (%) from run-in to double-blind phase was significantly higher compared with placebo-treated subjects (+36.7 vs. +12.1, P = 0.0185). Stool consistency improved significantly more with Creon 10 than with placebo (P = 0.0102) resulting in more subjects with formed stool; stool frequency decreased significantly more with Creon 10 than with placebo (P = 0.0015) from 10.8 during placebo run-in to 5.2 stools per day during double-blind treatment; and daily mean fat excretion in stool decreased significantly more (-56.5 vs. -11.4 g/d, P = 0.0181) in Creon 10-treated subjects compared with placebo-treated subjects. Global disease symptom scores showed greater improvement for both physicians and subjects in the Creon 10 group relative to those receiving placebo. Between treatment difference reached statistical significance for Creon 10 (P = 0.0435) for physician score and showed a trend (P = 0.0634) favoring Creon for subject score.
                This randomized, placebo-controlled trial found that Creon 10 treatment controlled steatorrhea, as reflected in reduced fat excretion, decreased stool frequency and improved stool consistency. Creon 10 treatment was safe and well tolerated. Chronic pancreatitis often culminates in maldigestion and diabetes. Clinical management is complex as the correction of maldigestion often disturbs diabetic control.
                In the following study, we examined the effects of a potent new commercial pancreatic enzyme on food absorption and blood glucose control. Enzymes were manufactured in enteric-coated mini-microsphere form (0.7--1.6 mm), designed to prevent gastric acid degradation and facilitate co-migration with food, and given in quantities calculated to cover normal digestion requirements (four capsules with meals, two with snacks; content/capsule: lipase 10,000 USP units, protease 37,500 units, amylase 33,200 units). Forty patients with chronic pancreatitis were screened during a run-in nonenzyme-supplemented phase; only those with stool fat excretion rates over 10 g/d (n = 29) were advanced to a 14-day parallel randomized placebo versus enzyme supplement group comparison.
                Of these, 62% were diabetic (50% insulin-dependent) and 52% were malnourished (body mass index less than 20 kg/m(2) ). After enzyme supplementation, stool fat and nitrogen excretion decreased, whereas fat absorption increased from 54.0 +/- 9.7% to 80.8 +/- 3.8% per day (p = 0.002) and protein from 80.5 +/- 3.4% to 86.8 +/- 2.2% per day (p = 0.004). Changing treatment from active enzyme supplementation to placebo (and vice versa) resulted in major problems with glucose control; blood glucose levels became abnormal in 28 of 29 patients, one patient required hospitalization for symptomatic hypoglycemia (0.9 mmol/L) during placebo treatment, and one developed diabetic ketoacidosis after recommencing active enzyme supplementation.
                In conclusion, high-dose pancreatin mini-microspheres improved, but did not normalize, fat absorption, possibly because of the residual influence of diabetes and malnutrition on absorptive function. In view of the brittle nature of blood glucose control in malnourished insulin-dependent patients, enzyme adjustment should be carefully supervised in-hospital. Oral pancreatic enzyme supplements should be properly administered in order to ensure an adequate gastric mixing with the food and simultaneous gastric emptying with the chyme.
                To evaluate, in a prospective, randomized, open, comparative, three-way, crossover study, the effect of the administration schedule on the efficacy of oral pancreatic enzymes for the treatment of exocrine pancreatic insufficiency.
                Twenty-four consecutive chronic pancreatitis patients with maldigestion secondary to exocrine pancreatic insufficiency were treated with 40 000 U lipase in the form of capsules containing enteric-coated mini-microspheres. Capsules were taken just before meals (schedule A), just after meals (schedule B) or distributed along with meals (schedule C) for three consecutive 1-week crossover periods in a randomized order. Fat digestion before and during the three treatment periods was evaluated by an optimized mixed (13)C-triglyceride breath test.
                Before therapy, the (13)CO(2) recovery in the breath test was 23.8 +/- 15.8% (normal >58.0%). During therapy, the (13)CO(2) recovery tended to be higher when capsules were taken along with meals ((13)CO(2) recovery 61.4 +/- 21.4%) or just after meals ((13)CO(2) recovery 60.6 +/- 21.8%) than when taken just before meals ((13)CO(2) recovery 53.9 +/- 20.3%). The percentage of patients who normalized fat digestion under therapy was 50, 54 and 63% with schedules A, B and C respectively.
                The efficacy of pancreatic enzyme supplements for the treatment of exocrine pancreatic insufficiency may be optimized by administration during or after meals.
The role of pancreatic enzymes for abdominal pain, weight loss, steatorrhoea, analgesic use and quality of life in patients with chronic pancreatitis remains equivocal. Good quality, adequately powered studies are much warranted.