Polymeric enteral diets as primary treatment of active Crohn's disease: a prospective steroid controlled trial.

Thirty two patients with active Crohn's disease were included in a controlled randomised trial to determine the efficacy and safety of polymeric enteral nutrition compared with steroids, to achieve and maintain clinical remission. The polymeric diet was administered through a fine bore nasogastric tube by continuous, pump assisted infusion (2800 (SEM 120) kcal/day). The steroid group received 1 mg/kg/day of prednisone. Both treatments were effective in inducing clinical remission: 15 of the 17 patients given steroids and 12 of the 15 patients assigned to the polymeric diet went into clinical remission (defined by a Van Hees index < 120) within four weeks of treatment. The percentage reduction of the Van Hees index was 34.8 (4.9)% for steroids and 32.3 (5)% for enteral nutrition (mean difference 2.5%; 95% CI--11.8% to +16.8%). Mean time elapsed to achieve remission was similar in both groups (2.0 (1) v 2.4 (1.2) weeks). Tolerance of the enteral diet was excellent. Four patients in the steroid group had mild complications attributable to this treatment. Ten patients (66.6%) in the steroid group and five (41.6%) in the enteral nutrition group relapsed within a year of discharge, but no differences were found in the cumulative probability of relapse during the follow up period. These results suggest that polymeric enteral nutrition is as safe and effective as steroids in inducing short term remission in active Crohn's disease.     

Peripheral parenteral nutrition is no better than enteral nutrition in acute exacerbation of Crohn's disease: a prospective trial

The use of parenteral nutrition in patients with exacerbation of regional enteritis is controversial, the clinical dictum being bowel rest and nutritional repletion. In order to address this issue, on the short-term at least, a prospective randomized trial compared peripheral parenteral alimentation and elemental feedings for 2 weeks in patients hospitalized with regional enterities. Both groups had significant objective clinical improvement on their respective nutritional supplementation regimens pre- versus posttherapy as assessed by the Crohn's Disease Activity Index (CDAI) (p less than 0.05). However, there was no significant difference in improvement between parenteral versus enteral groups as assessed by the CDAI. Changes in nutritional assessment parameters, including retinol binding protein, nitrogen balance, total lymphocyte count, and transferrin, were related to the quantity of calories consumed rather than the mode of delivery. A positive nitrogen balance was obtained in all patients despite weight loss in the majority. The route of nutrient delivery in acute exacerbation of regional enteritis does not appear to have an impact on the short-term outcome.     

A randomised controlled trial of high versus low long chain triglyceride whole protein feed in active Crohn's disease

BACKGROUND: Polymeric feeds have shown variable efficacy in active Crohn's disease (CD) with remission rates from 36% to 82%. Meta-analyses of elemental, peptide, and whole protein feeds have shown a strong negative correlation between remission rate in CD and the long chain triglyceride (LCT) content of the feed. We performed a randomised controlled double blind trial in patients with active CD comparing two single whole protein feeds with LCT supplying 5% or 30% of the total energy. METHODS: Fifty four patients with active CD (Crohn's disease activity index (CDAI) >200, serum C reactive protein (CRP) 10 mg/l) were randomised to a high or low LCT feed for three weeks. The total amount of energy supplied by fat was identical in the two feeds. Remission was defined as a CDAI < or =150 and response as a fall in CDAI of > or =70 or a CRP <10 mg/l. RESULTS: Overall remission rate by intention to treat was 26% for the low LCT feed and 33% for the high LCT feed (p=0.38). Response was achieved in 33% with the low LCT and in 52% with the high LCT feed (p=0.27). CRP <10 mg/l was achieved in 30% in the low LCT and 33% in the high LCT group (p=0.99). Thirty nine per cent (21/54) of patients withdrew before three weeks because of inability to tolerate the diet. Excluding patients unable to tolerate the diet, remission rates were 46% for low LCT and 45% for high LCT (p=0.99). DISCUSSION: This trial has shown no difference in the effect of low and high LCT whole protein feeds in active CD. The previously reported correlation between LCT content of diet and response in active CD is unlikely to be due to LCT itself and may be due to some other component of high LCT feeds.     

Enteral nutrition in Crohn's disease: fat in the formula

Enteral nutrition is effective in inducing remission in active Crohn's disease. Speculation on the underlying mechanism of action has moved away from the presentation of nitrogen and towards the fat content of the various enteral feeds. Evidence is accumulating that additional long-chain triglyceride in such feeds impairs the response rate in active Crohn's disease, whereas no deleterious effects of additional medium-chain triglyceride have been identified. It has been proposed that long-chain triglycerides composed from n-6 fatty acids may be the most harmful, since such fatty acids are substrates for inflammatory eicosanoid production. However, recent studies comparing different enteral feeds are not consistent in identifying which additional fatty acids impair response rates to the greatest extent. Despite meta-analyses concluding that polymeric diets (typically containing large amounts of fat) are as effective as elemental diets, it would seem sensible to use enteral feeds with minimal fat content when treating active Crohn's disease.     

Combined budesonide and antibiotic therapy for active Crohn's disease: a randomized controlled trial

BACKGROUND & AIMS: Although antibiotics are frequently used to treat Crohn's disease, this practice is not supported by strong evidence from randomized trials. METHODS: We conducted a double-blind multicenter study of patients with active Crohn's disease of the ileum, right colon, or both. Patients were randomized to receive oral ciprofloxacin and metronidazole, both 500 mg twice daily, or placebo for 8 weeks. All patients received oral budesonide 9 mg once daily. The primary efficacy measure was the proportion of patients in remission at week 8. RESULTS: Of the 134 patients who were randomized, 130 were evaluated for efficacy; 66 received placebo, and 64 received antibiotics. At week 8, 21 patients (33%) assigned to antibiotics were in remission as compared with 25 patients (38%) in the placebo group (P = 0.55; absolute difference, -5%; 95% confidence interval, -21% to 11%). An interaction (P = 0.025) between treatment allocation and disease location on treatment response was identified. Among patients with disease of the colon, 9 of 17 (53%) were in remission after treatment with antibiotics, compared with 4 of 16 (25%) of those who received placebo (P = 0.10). Discontinuation of therapy because of adverse events occurred in 13 of 66 (20%) patients treated with antibiotics, compared with 0 of 68 in the group who received placebo (P < 0.001). CONCLUSIONS: In patients with active Crohn's disease of the ileum, the addition of ciprofloxacin and metronidazole to budesonide is an ineffective intervention, but this antibiotic combination may improve outcome when there is involvement of the colon.     

Exclusive enteral nutrition in children with crohn's disease

Exclusive enteral nutrition involves the use of a complete liquid diet, with the exclusion of normal dietary components for a defined period of time,as a therapeutic measure to induce remission in active Crohn's disease(CD). This very efficacious approach leads to high rates of remission, especially in children and adolescents newly diagnosed with CD. This intervention also results in mucosal healing,nutritional improvements and enhanced bone health.Whilst several recent studies have provided further elaboration of the roles of exclusive enteral nutrition in the management of CD, other reports have provided new understanding of the mechanisms by which this intervention acts.     

Selenium is depleted in Crohn's disease on enteral nutrition

BACKGROUD/AIMS: Selenium is an important trace element and its deficiency has been reported to be associated with cardiomyopathy or gastrointestinal cancer. The aim of this study is to clarify the selenium status in Crohn's disease (CD) on enteral nutrition. METHODS: We measured serum selenium concentrations in 53 patients with CD and compared them with those in 21 healthy controls. Twenty-nine patients were under the treatment by enteral nutrition (EN group), and the remaining 24 patients were free from formulated enteral nutrition (non-EN group). RESULTS: While the serum selenium concentration in the non-EN group was not decreased when compared to controls, the value in the EN group was significantly lower than those in the non-EN group and in controls. Clinical manifestations of selenium deficiency were found in a patient on exclusive enteral nutrition. In the EN group, the serum selenium concentration showed an inverse correlation with the duration and the daily dose of enteral nutrition. In the non-EN group, the serum selenium concentrations were inversely correlated with the Crohn's disease activity index. CONCLUSION: These findings suggest that patients with CD on enteral nutrition are at risk for selenium deficiency and that even patients without enteral nutrition may develop selenium deficiency at the active phase of the disease.     

Energy expenditure and body composition in children with Crohn's disease: effect of enteral nutrition and treatment with prednisolone

Background—Malnutrition and growth retardation arecommon complications of Crohn's disease in children. The contributionof resting energy expenditure (REE) to malnutrition is unclear.
Aims—To characterise the REE and body compositionin children with Crohn's disease and compare them with normal controlsand patients with anorexia nervosa; to compare the effects ofprednisolone and enteral nutrition on energy expenditure and body composition.
Subjects—Twenty four children with Crohn'sdisease, 19 malnourished females with anorexia nervosa, and 22 healthycontrol subjects were studied.
Methods—In children with Crohn's diseasemeasurements were done when the disease was acute and repeated at oneand three months after treatment with either prednisolone or enteralnutrition. Resting energy expenditure was measured by indirectcalorimetry and body composition by anthropometry, bioelectricalimpedance analysis, total body potassium,H₂¹⁸O, and bromide space studies.
Results—Body weight and ideal body weight weresignificantly lower in patients with Crohn's disease than in healthycontrols. Lean tissue was depleted and there was an increase inextracellular water. Per unit of lean body mass, there was nodifference between REE in patients with Crohn's disease and controls,whereas patients with anorexia nervosa had significantly reduced REE.With enteral nutrition all body compartments and REE increasedsignificantly (p<0.001). In a subgroup of age-matched men there was asignificant increase in height after three months of enteral nutritioncompared with prednisolone (p<0.01). Those treated with steroids didnot show a significant change in height but did show an increase in allbody compartments. However, intracellular water as well as lean bodymass accretion were significantly higher in the enteral nutrition groupthan in the prednisolone group.
Conclusions—Despite being malnourished, childrenwith Crohn's disease fail to adapt their REE per unit of lean bodymass. This might be a factor contributing to their malnutrition. Lean tissue accretion is higher in patients treated with enteral nutrition than in those treated with prednisolone.

Keywords:Crohn's disease; resting energy expenditure; bodycomposition; anorexia nervosa; prednisolone; enteral nutrition

     

Fat composition may be a clue to explain the primary therapeutic effect of enteral nutrition in Crohn's disease: results of a double blind randomised multicentre European trial

BACKGROUND: Dietary fat has been suggested to determine the therapeutic effect of enteral diets in Crohn's disease. AIM: To assess the efficacy of two whole protein based diets with different fat compositions (n6 polyunsaturated fatty acids v monounsaturated fatty acids) in inducing clinical remission in active Crohn's disease compared with steroids. METHODS: Sixty two patients with active Crohn's disease were randomised to receive, for not more than 4 weeks: (a) a polymeric enteral diet containing 35 g of lipids per 1000 kcal, high in oleate (79%) and low in linoleate (6.5%) (PEN1), (b) an identical enteral diet except for the type of fat which was high in linoleate (45%) and low in oleate (28%) (PEN2), or (c) oral prednisone (1 mg/kg/day). Diets were double blindly administered. The steroid group received a conventional ward diet. Treatment failure was considered when remission was not achieved at week 4. Clinical activity and biological and nutritional parameters were monitored. Independent predictors of remission were identified by stepwise logistic regression analysis. RESULTS: Overall remission rates (by intention to treat) were 20% (4/20) for PEN1, 52% (12/23) for PEN2, and 79% (15/19) for steroids (overall p=0.001; p<0.0005 steroids v PEN1, and p=0.056 PEN2 v PEN1). After excluding those patients who were non-compliant during the first week (per protocol analysis), remission rates were 27%, 63%, and 79%, respectively (p=0.008, steroids and PEN2 v PEN1). After adjusting for confounding variables, PEN1 remained significantly associated with a poor response. CONCLUSION: The type of dietary fat may be of importance for the primary therapeutic effect of enteral nutrition in active Crohn's disease.     

Ineffectiveness of probiotics in preventing recurrence after curative resection for Crohn's disease: a randomised controlled trial with Lactobacillus GG

BACKGROUND AND AIMS: Experimental studies have shown that luminal bacteria may be involved in Crohn's disease. Probiotics are a possible alternative to antibiotics. The aim of this randomised placebo controlled study was to determine if Lactobacillus GG, given by mouth for one year, could prevent Crohn's recurrent lesions after surgery or to reduce their severity. METHODS: Patients operated on for Crohn's disease in whom all of the diseased gut had been removed were randomly allocated to receive 12 billion colony forming units of Lactobacillus or identical placebo for one year. Ileocolonoscopy was performed at the end of the trial or at the onset of symptoms. Endoscopic recurrence was defined as grade 2 or higher of Rutgeerts scoring system. RESULTS: Eight of 45 patients were excluded from the trial (three for non-compliance and five for protocol violations). Clinical recurrence was ascertained in three (16.6%) patients who received Lactobacillus and in two (10.5%) who received placebo. Nine of 15 patients in clinical remission on Lactobacillus (60%) had endoscopic recurrence compared with six of 17 (35.3%) on placebo (p=0.297). There were no significant differences in the severity of the lesions between the two groups. CONCLUSIONS: Lactobacillus GG seems neither to prevent endoscopic recurrence at one year nor reduce the severity of recurrent lesions.     

Supplementary enteral nutrition maintains remission in paediatric Crohn's disease.

BACKGROUND--Liquid diets given enterally combined with "bowel rest'' are efficacious in the treatment of active Crohn''s disease, but rapid recrudescence of gastrointestinal symptoms after resumption of a normal diet is common. AIMS--This study examined whether continuation of enteral nutrition as a nocturnal supplement to an ad libitum daytime intake of a normal diet increased the length of remission of Crohn''s disease in children. PATIENTS AND METHODS--Children and adolescents with active Crohn''s disease treated successfully with exclusive enteral nutrition were classified retrospectively according to whether they continued supplementary enteral nutrition or not. Time to relapse and linear growth were compared between the two cohorts. RESULTS--Between January 1986 and December 1992, 65 patients aged 7-17 years (mean (SD) 13.6 (2.1) years) (36 males, 29 females) with Crohn''s disease in exacerbation were treated for > or = four weeks by bowel rest and nasogastric tube feeding of an oligopeptide or amino acid based formula. At first follow up visit, remission (fall in Paediatric Crohn''s Disease Activity Index, PCDAI to < or = 20) was achieved in 47 of 65 (72%) patients. Subsequently, 20 of these 47 (43%) relapsed by six months and 28 of 47 (60%) by 12 months. Patients who continued nasogastric supplementary feeding (n = 28) after resumption of an otherwise normal diet remained well longer than those who discontinued nocturnal supplements completely (n = 19) (p < 0.02). Furthermore, continued use of nasogastric supplements before completion of puberty was associated with improved linear growth. CONCLUSION--After successful treatment of active Crohn''s disease by exclusive enteral nutrition, supplementary enteral nutrition without restriction of normal diet is associated with prolongation of remission and improved linear growth in children and adolescents.     

Budesonide versus prednisolone for the treatment of active Crohn's disease in children: a randomized, double-blind, controlled, multicentre trial

OBJECTIVES: Budesonide is a corticosteroid with low systemic bioavailability because of its high first-pass metabolism in the liver. In this paediatric, randomized, double-blind, double-dummy, controlled, multicentre trial, the safety and efficacy of budesonide versus prednisolone were evaluated in children with active Crohn's disease. METHODS: Forty-eight children, aged 6-16 years, with active Crohn's disease (Crohn's Disease Activity Index > 200) involving ileum and/or ascending colon were randomized to receive budesonide (9 mg/day for 8 weeks, 6 mg/day for 4 weeks) or prednisolone (1 mg/kg/day for 4 weeks, tapering for 8 weeks). RESULTS: The groups were comparable for age, sex, pubertal stage, disease activity and disease duration. Mean morning plasma cortisol concentration was significantly higher in the budesonide group (200 nmol/l) than in the prednisolone group (98 nmol/l) after 8 weeks, reflecting less adrenal suppression by budesonide (difference -102 nmol/l; 95% CI -226, -52; P = 0.0028). Glucocorticosteroid side effects such as moon face and acne occurred significantly less frequently in the budesonide group. Remission (Crohn's Disease Activity Index < or = 150) was seen at 8 weeks in 12/22 (55%) patients treated with budesonide and in 17/24 (71%) patients receiving prednisolone (difference -16%; 95% CI -45,13; P = 0.25). CONCLUSIONS: Significantly fewer side effects and less adrenal suppression were observed in the children receiving budesonide. Remission rates were not significantly different in the two groups. However, there was a trend for prednisolone to be more effective for inducing remission.