Human growth hormone and glutamine for patients with
`short bowel syndrome (Review)
`
`Wales PW, Nasr A, de Silva N, Yamada J
`
`This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library
`2010, Issue 6
`
`http://www.thecochranelibrary.com
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`Human growth hormone and glutamine for patients with short bowel syndrome (Review)
`Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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`T A B L E O F C O N T E N T S
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`HEADER .
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`ABSTRACT .
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`PLAIN LANGUAGE SUMMARY
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`BACKGROUND .
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`OBJECTIVES
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`METHODS .
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`RESULTS .
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`Figure 1.
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`Figure 2.
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`Figure 3.
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`Figure 4.
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`Figure 5.
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`DISCUSSION .
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`AUTHORS’ CONCLUSIONS
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`ACKNOWLEDGEMENTS
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`REFERENCES .
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`CHARACTERISTICS OF STUDIES
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`DATA AND ANALYSES .
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`Analysis 1.1. Comparison 1 Comparison of growth hormone with or without glutamine versus placebo, Outcome 1
`Change in weight (Kg).
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`Analysis 1.2. Comparison 1 Comparison of growth hormone with or without glutamine versus placebo, Outcome 2
`Change in Lean Body Mass (Kg).
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`Analysis 1.3. Comparison 1 Comparison of growth hormone with or without glutamine versus placebo, Outcome 3
`Change in Energy absorption (Kcal).
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`Analysis 1.4. Comparison 1 Comparison of growth hormone with or without glutamine versus placebo, Outcome 4
`Change in carbohydrates absorption (g).
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`Analysis 1.5. Comparison 1 Comparison of growth hormone with or without glutamine versus placebo, Outcome 5
`Change in fat absorption (g).
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`Analysis 1.6. Comparison 1 Comparison of growth hormone with or without glutamine versus placebo, Outcome 6
`Change in nitrogen absorption (g).
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`Analysis 2.1. Comparison 2 Comparison of Growth Hormone versus placebo, Outcome 1 Change in weight (Kg).
`Analysis 2.2. Comparison 2 Comparison of Growth Hormone versus placebo, Outcome 2 Change in Lean Body Mass
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`Analysis 2.3. Comparison 2 Comparison of Growth Hormone versus placebo, Outcome 3 Change in energy absorption
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`Analysis 2.4. Comparison 2 Comparison of Growth Hormone versus placebo, Outcome 4 Change in nitrogen absorption
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`Analysis 3.1. Comparison 3 Studies with short durations (4 weeks or less), Outcome 1 Change in weight (Kg).
`Analysis 3.2. Comparison 3 Studies with short durations (4 weeks or less), Outcome 2 Change in Lean Body mass (Kg).
`Analysis 3.3. Comparison 3 Studies with short durations (4 weeks or less), Outcome 3 Change in energy absorption
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`Analysis 3.4. Comparison 3 Studies with short durations (4 weeks or less), Outcome 4 Change in nitrogen absorption (g).
`Analysis 4.1. Comparison 4 Studies with high treatment dose, Outcome 1 Change in weight.
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`Analysis 4.2. Comparison 4 Studies with high treatment dose, Outcome 2 Change in Lean Body Mass.
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`Analysis 4.3. Comparison 4 Studies with high treatment dose, Outcome 3 Change in Energy absorption (Kcal).
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`Analysis 4.4. Comparison 4 Studies with high treatment dose, Outcome 4 Change in nitrogen absorption (g).
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`WHAT’S NEW .
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`CONTRIBUTIONS OF AUTHORS
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`DECLARATIONS OF INTEREST .
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`SOURCES OF SUPPORT .
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`INDEX TERMS
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`Human growth hormone and glutamine for patients with short bowel syndrome (Review)
`Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
`
`Page 2
`
`

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`[Intervention Review]
`
`Human growth hormone and glutamine for patients with
`short bowel syndrome
`
`Paul W Wales1, Ahmed Nasr2, Nicole de Silva3, Janet Yamada4
`
`1Division of General Surgery and Group for Improvement of Intestinal Function and Treatment (GIFT), The Hospital for Sick
`Children, Toronto, Canada. 2Division of General Surgery, The Hospital for Sick Children, Toronto, Canada. 3Neonatology and Group
`for Improvement of Intestinal Function and Treatment (GIFT), The Hospital for Sick Children, Toronto, Canada. 4Nursing, The
`Hospital for Sick Children, Toronto, Canada
`
`Contact address: Paul W Wales, Division of General Surgery and Group for Improvement of Intestinal Function and Treatment (GIFT),
`The Hospital for Sick Children, Rm 1526, 555 University Ave, Toronto, Ontario, M5G 1X8, Canada. paul.wales@sickkids.ca.
`
`Editorial group: Cochrane IBD Group.
`Publication status and date: New, published in Issue 6, 2010.
`Review content assessed as up-to-date: 30 December 2009.
`
`Citation: Wales PW, Nasr A, de Silva N, Yamada J. Human growth hormone and glutamine for patients with short bowel syndrome.
`Cochrane Database of Systematic Reviews 2010, Issue 6. Art. No.: CD006321. DOI: 10.1002/14651858.CD006321.pub2.
`
`Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
`
`Background
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`A B S T R A C T
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`There has been clinical enthusiasm for treating short bowel patients with human recombinant growth hormone and/or glutamine in
`hopes of reducing parenteral nutrition dependency. It has been more than a decade since Byrne and colleagues reported enhanced
`absorption of nutrients, improved weight gain, and reduction in parenteral nutrition requirements with the administration of a
`combination of human growth hormone (HGH) and glutamine in patients with short bowel syndrome. Other studies have reported
`inconsistent results.
`
`Objectives
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`The purpose of this systematic review was to evaluate the efficacy of growth hormone with or without glutamine supplementation for
`adult patients with short bowel syndrome.
`
`Search methods
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`Electronic searches were performed to identify all publications describing randomised controlled trials of the use of human growth
`hormone with or without glutamine for the treatment of patients with short bowel syndrome.
`
`Selection criteria
`
`Randomised controlled trials of human growth hormone with or without glutamine for patients with short bowel syndrome were
`considered for inclusion.
`
`Data collection and analysis
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`Two authors independently extracted data from the published studies. The statistical analyses were performed using RevMan 5 software.
`Follmann’s method was used for cross-over studies.
`
`Human growth hormone and glutamine for patients with short bowel syndrome (Review)
`Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
`
`1
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`Page 3
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`Main results
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`Five studies were included in the review. Human growth hormone with or without glutamine appears to provide benefit in terms of
`increased weight (MD 1.66 Kg; 95% CI 0.69 to 2.63;P = 0.0008), lean body mass (MD 1.93 Kg; 95% CI 0.97 to 2.90; P = 0.0001)
`energy absorption (MD 4.42 Kcal; 95% CI 0.26 to 8.58; P = 0.04) and nitrogen absorption (MD 44.85 g; 95%CI 0.20 to 9.49; P =
`0.04) for patients with short bowel syndrome. The single RCT that focused on parenteral nutrition (PN) requirements demonstrated
`decreased PN volume and calories and number of infusions in patients who received HGH with or without glutamine supplementation.
`Only patients who received HGH with glutamine maintained statistically significant PN reductions at 3 month follow-up.
`
`Authors’ conclusions
`
`The results suggest a positive effect of human growth hormone on weight gain and energy absorption. However, in the majority of
`trials, the effects are short-lived returning to baseline shortly after cessation of therapy. The temporary benefit calls into question the
`clinical utility of this treatment. To date, the evidence is inconclusive to recommend this therapy. Consideration should be made to
`studying patients during the active phase of intestinal adaptation rather than in the setting of chronic intestinal failure. The role of
`HGH in paediatric short bowel syndrome remains unknown.
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`P L A I N L A N G U A G E S U M M A R Y
`
`Human growth hormone and glutamine for patients with short bowel syndrome
`
`Short bowel syndrome is a malabsorption disorder caused by the surgical removal of the small intestine, or by the complete dysfunction
`of a large segment of bowel. It is a challenging health problem to treat. Several small studies have assessed the benefit of providing drugs
`such as human growth hormone and glutamine in an attempt to improve intestinal function and wean intravenous nutrition (liquid
`food). The results of this review of 5 small studies suggest that human growth hormone used with or without glutamine may provide
`short term benefit for patients with short bowel syndrome in terms of weight gain and intestinal absorption of nutrients. However the
`benefits of treatment do not continue after treatment is stopped. Common side effects of treatment include peripheral edema (swelling
`of tissues, usually in the lower limbs), and carpal tunnel syndrome (numbness and muscle weakness in the hand). Conclusive evidence
`is not available to recommend this treatment. Further studies that evaluate human growth hormone treatment during the immediate
`phase of bowel adaptation are needed.
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`B A C K G R O U N D
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`Patients who undergo extensive resection of the gastrointestinal
`tract may subsequently develop intestinal failure secondary to
`short-bowel syndrome. Intestinal failure occurs in the absence of
`minimum intestinal mass required for adequate digestion and ab-
`sorption of nutrients leading to malnutrition and/or dehydration.
`Depending on the extent, degree, and location of the resection,
`patients may experience severe malabsorption of fluid, electrolytes,
`and other nutrients (Li-Ling 2001). Many of these patients be-
`come dependent on long-term parenteral nutrition. Due to the
`potential complications, cost, and quality of life issues, alternative
`therapies to parenteral nutrition such as aggressive intestinal re-
`habilitation and small bowel transplantation have been developed
`(Thompson 1993; Abu-Elmagd 1994).
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`Intestinal adaptation, first described by Flint (Flint 1912) is a
`process whereby the remnant bowel begins to compensate for
`the loss of the resected portion following small bowel resection.
`It is believed that this adaptive phase continues for 2 years in
`adults (Messing 1999;Nighttingale 1999). The exact mechanism
`by which these alterations in bowel morphology and function oc-
`cur is not known, but the process includes both structural and
`functional aspects (Nighttingale 1993). During this process the
`bowel dilates and elongates and there is an increase in villus height,
`crypt depth, cell proliferation and enzyme activity. This results
`in enhanced fluid, electrolyte, and nutrient absorption as well as
`prolonged transit time (Flint 1912).
`
`Intestinal adaptation occurs in response to enteral nutrition, in-
`testinal secretions and hormonal factors. Trophic changes have
`
`Human growth hormone and glutamine for patients with short bowel syndrome (Review)
`Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
`
`2
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`Page 4
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`been observed in animals when various growth factors such as
`growth hormone, insulin-like growth factor-1, glucagon-like pep-
`tide-2, specific nutrients such as glutamine, short-chain fatty acids,
`pancreatic-biliary secretions are supplemented (Rhoads 1991;
`Tamada 1993; Souba 1985; Jacobs 1983; Gardemann 1992). To-
`gether these trophic stimuli allow the remnant bowel to adapt
`(hypertrophy). Attempts to increase the absorptive capacity of
`the remnant bowel have been made by promoting pharmacologic
`adaptation through the use of hormonal intestinal trophic factors
`(Lentze 1989).
`
`Byrne and colleagues first demonstrated, through an open label
`clinical trial and a case series (Byrne 1995a; Byrne 1995b), the
`benefit to intestinal adaptation by administering growth hormone
`and glutamine in ten patients with remnant small intestine who
`had been on long term parenteral nutrition. These results attracted
`much interest and in the following years several other trials were
`published. A few case series were published suggesting the ben-
`efit of both human growth hormone (HGH) and glutamine in
`patients with short bowel (Scheppach 1994; Inoue 1994). How-
`ever, controversy still surrounds the use of growth hormone and
`glutamine in these patients. The number of studies in this area is
`limited and the results are conflicting.
`
`On the basis of previous animal studies, it appears that the com-
`bination of GH and glutamine has a synergistic effect on intesti-
`nal function (Gu 2001; Ziegler 1996). Glutamine is a required
`substrate for ornithine decarboxylase and an essential precursor
`for nucleotide biosynthesis. Certainly, there is no reason to sug-
`gest a negative or cancelling effect when glutamine is given with
`HGH. There appears to be no carry over effect using these drugs
`in a cross-over design, due to its confirmed short half life (Li-Ling
`2001).
`
`O B J E C T I V E S
`
`The purpose of this systematic review was to evaluate the efficacy
`of growth hormone with or without glutamine supplementation
`for adult patients with short bowel syndrome.
`
`M E T H O D S
`
`Criteria for considering studies for this review
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`Types of studies
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`Randomised controlled trials of human growth hormone with or
`without glutamine for patients with short bowel syndrome were
`considered for inclusion. Letters, editorials, commentaries, reviews
`and lectures that do not contain original research data and studies
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`that used historical controls were excluded. For studies in which
`further data were required the authors were contacted for further
`information.
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`Types of participants
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`Adult patients diagnosed with short bowel syndrome and depen-
`dent on parenteral nutrition support were considered for inclu-
`sion. Short bowel syndrome was defined as “reduction of function-
`ing gut mass below the amount necessary for adequate digestion
`and absorption of nutrients”.
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`Types of interventions
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`Studies in which human recombinant growth hormone with or
`without glutamine were compared to placebo were considered for
`inclusion.
`
`Types of outcome measures
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`Studies were considered for inclusion if they reported on one or
`more of the following outcomes:
`Primary outcome: Change in body weight (Kg); and
`Secondary outcomes:
`• Change in lean body mass (LBM) in Kg (measured using
`Dual energy x ray or bioelectric impedance analysis);
`• Change in total energy absorption in Kcal (measured using
`bomb calorimetry or by subtracting the amount of energy
`excreted in stool output from that actually ingested);
`• Changes in fat, carbohydrate and nitrogen absorption in
`grams (measured as the difference between intake and fecal loss);
`• Change in serum level of insulin-like growth factor-1 (IGF-
`1) ng/mL (measured by radio-immunoassay);
`• Change in parenteral nutrition requirements; and
`• Adverse events related to the intervention.
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`Adverse events related to the intervention included:
`A) Proportion of patients developing peripheral edema;
`B)Proportion of patients developing arthralgia; and
`C)Proportion of patients developing carpal tunnel syndrome.
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`Search methods for identification of studies
`
`All publications describing randomised controlled trials of the
`use of human growth hormone with or without glutamine were
`sought through the Cochrane IBD/FBD Group Trials Register,
`and the Cochrane Central Register of Controlled Trials (CEN-
`TRAL) database. All studies were identified through electronic
`searches of MEDLINE (1966 to December 31, 2009), EMBASE
`(1980 to Dec 31, 2009), and CINAHL (1982 to December 31,
`2009), and conference proceedings.
`Databases were searched using the following search terms: “growth
`hormone,” “glutamine,” “intestinal rehabilitation,” “intestinal
`
`Human growth hormone and glutamine for patients with short bowel syndrome (Review)
`Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
`
`3
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`Page 5
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`failure”, “malabsorption” and “short-
`adaptation,” “intestinal
`bowel syndrome.” There were no language restrictions.
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`R E S U L T S
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`Data collection and analysis
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`Selection of trials
`Four authors (AN, YJ, ND and PW) independently assessed all
`published articles identified as potentially relevant by the literature
`search for inclusion in the review using the criteria outlined above.
`Evaluation of methodological quality of trials
`Standard methods of the Cochrane Inflammatory Bowel Disease
`and Functional Disorder Group were used to assess the method-
`ological quality of studies.
`Two authors (AN,JY) independently assessed the quality of the in-
`cluded studies using the Cochrane risk of bias tool (Higgins 2008):
`An assessment was made of the method of allocation generation
`(i.e. was the allocation sequence adequately generated?), allocation
`concealment (i.e. was allocation adequately concealed?), blinding
`(i.e. was knowledge of the allocated intervention adequately pre-
`vented during the study?), and incomplete outcome data (i.e. were
`incomplete outcome data adequately addressed?). A judgement of
`’Yes’ indicates low risk of bias, ’No’ indicates high risk of bias, and
`’Unclear’ indicates unclear or unknown risk of bias.
`Data extraction
`Two authors (AN and JY) independently extracted data from the
`retrieved articles. The primary authors of any articles for which
`there was inadequate data were contacted for further information.
`Any discrepancies were resolved by discussion and consensus with
`a third reviewer.
`Statistical analysis
`The statistical analysis was performed using RevMan 5 software.
`Heterogeneity was assessed using the chi-square (Q test) and the
`I2 statistic. If the results of these tests showed heterogeneity, using
`a cut-off of 0.10 or larger in the Q test or more than 50% hetero-
`geneity using the I2 statistic, a random effects model was used for
`meta-analysis. Follmann’s method was used for cross-over studies.
`A correlation coefficient of 0.4 was used to calculate the standard
`error of the mean difference. The quantities of the mean difference
`and the standard error of the mean difference were then entered
`into RevMan and analysed using a generic inverse variance out-
`come. Sensitivity analyses were performed using correlation coef-
`ficients of 0.3 and 0.5 to test the robustness of the results.
`Subgroup analysis included:
`• Patients given only HGH;
`• Long versus short duration of treatment (4 weeks duration
`as a cut-off );
`• Inflammatory versus non-inflammatory cause of short
`bowel; and
`• Presence / absence of colon.
`
`Description of studies
`
`The literature search identified nine randomised controlled trials
`that were considered for inclusion. Two studies were excluded.
`Byrne 1995a was excluded because it was a non-randomised trial.
`Scoplapio 2001 was excluded because it used glutamine without
`HGH. Of the seven remaining studies two studies were secondary
`publications (Scolapio 1999; Jeppesen 2001) of the same patients
`with different outcomes of the Scolapio 1997 and Szkudlarek 2000
`studies respectively. Therefore, five studies were included in this
`review.
`Participants
`
`Ellegård 1997 was a randomised, double-blind, placebo-controlled
`crossover study. Criteria for eligibility included stable short bowel
`syndrome, i.e., at least 10% below premorbid body weight with
`stable (± 2 Kg) weight and nutritional support during the last 6
`months. Ten patients (3 women, 7 men, mean age 49 years, range
`30 to 72 years) with short bowel syndrome due to surgery for
`Crohn’s disease were included in this trial. The mean small bowel
`length was 130 cm (range 90 to 170 cm). Four patients had an
`intact colon.
`The Scolapio 1997 trial was a randomised, double-blind, placebo-
`controlled crossover study. Eight patients with short bowel syn-
`drome (6 men, 2 women, mean age 12.9 years, range 3 to 19 years)
`who were dependent on home parenteral nutrition were included.
`Seven patients had short bowel syndrome due to Crohn’s disease
`and one following ischemia. The mean small bowel length was 71
`cm (range 55 to 120 cm). Two patients had an intact colon.
`Szkudlarek 2000 was a randomised, double-blind, placebo-con-
`trolled crossover study. The trial included 8 patients (one man,
`7 women, age range 32 to 74 years) with short bowel syndrome.
`Six patients had short bowel due to Crohn’s disease and 2 due to
`mesenteric infarction. The mean small bowel length was 100 cm;
`range 30-150 cm. Four of whom had their colon intact.
`Seguy 2003 performed a
`randomised, placebo-controlled
`crossover study in 12 patients (mean age 35 years, range 19-51)
`with established short bowel syndrome caused by Crohn’s (n =
`3), mesenteric infarction (n = 3), small bowel volvulus (n = 2),
`necrotising enterocolitis (n = 2), abdominal wall defect (n = 1) and
`radiation enteritis (n = 1). The mean small bowel length was 48
`cm (range 0 to 120 cm). Nine patients had a partial colon.
`Byrne 2005 performed a prospective, double-blind, randomised,
`placebo-controlled clinical trial in 41 adult short bowel syndrome
`patients adults dependent on parenteral nutrition (PN). Eligibil-
`ity criteria included: adults aged 18 to 75 years; body mass index
`(BMI) 17 to 28 kg/m2; small intestinal length ≤ 200 cm; the
`ability to ingest solid food while requiring ≥ 3000 PN calories/
`week; acceptable liver and kidney function; and normal or stable
`cardiovascular status. Patients had to have undergone bowel re-
`
`Human growth hormone and glutamine for patients with short bowel syndrome (Review)
`Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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`section ≥ 6 months prior to study, and had intact stomach and
`duodenum and one or more of the following: 1) >= 30% of colon
`anastomosed to ≥ 15 cm jejunum-ileum; 2) < 30% colon anas-
`tomosed to ≥ 90 cm jejunum-ileum; or 3) < 3 L stool output/
`day. Total length of residual bowel was documented at the time of
`resection or, if operative reports were unavailable or unclear, from
`radiographic examinations, which were used in 2 individuals.
`Intervention
`
`Ellegård 1997
`Recombinant HGH in a dose of (0.024 mg/kg/day) or identical
`placebo were administered subcutaneously each evening by the
`patients. Patients received the intervention or placebo for 8 weeks
`separated by a washout period of12 weeks.
`Scolapio 1997
`Active treatment included subcutaneous recombinant HGH (0.14
`mg/kg/day), oral glutamine (0.63 g/kg per day), and a high carbo-
`hydrate low fat diet for 21 days. Subcutaneous injections of nor-
`mal saline served as a placebo for HGH and polycose powder as a
`placebo for glutamine. A washout period was not reported.
`Szkudlarek 2000
`Active treatment consisted of subcutaneous recombinant HGH
`(0.14 mg/kg/day) divided into two daily injections, oral L-glu-
`tamine (30 g/day) divided into six doses, and parenteral glutamine
`as glutamine enriched infusions which matched the patients’ usual
`parenteral intake of amino acid nitrogen. Placebo treatment con-
`sisted of subcutaneous injections of saline serving as a control for
`growth hormone, L-alanine powder 30 g/day in six daily doses as a
`control for oral glutamine, and the patient’s usual parenteral pro-
`gramme as a control for the glutamine enriched solutions. Each
`treatment period lasted 28 days. There was no washout period
`between active treatment and placebo.
`Seguy 2003
`Treatment consisted of 3 weeks of recombinant HGH (0.05 mg/
`kg per day) without glutamine. Placebo vials contained water and
`were visually indistinguishable from active treatment. The two
`3-week treatment periods were separated by a 1 week washout
`period.
`Byrne 2005
`There were three treatment groups: 1) oral glutamine (30 g/day)
`+ subcutaneous HGH placebo; 2) oral glutamine placebo + sub-
`cutaneous HGH (0.1 mg/kg/day); or 3) oral glutamine + HGH
`(using the doses noted above).
`The first group, which represented the effects of optimal dietary in-
`take + oral Gln, served as a control. In-house treatment continued
`for 4 weeks. Throughout the in-house period, patients were mon-
`itored by taking vital signs, weight, oral and parenteral intakes,
`stool and urine output, bioelectrical impedance (model 101A, RJL
`Systems, Clinton, MI), and selected blood concentrations at ap-
`propriate intervals. The PN was adjusted based on pre-established
`weaning criteria.
`At the conclusion of the in-house period, patients were discharged
`
`home on the optimal diet with glutamine or glutamine placebo.
`Their discharge PN prescription was the same as that received
`during the last week of their in-house therapy. All patients were
`monitored by their physicians and the study team for the next
`3 months. If indicated by changes in nutritional and hydration
`status, adjustments were made in PN. At week 18, a physical
`examination, body weight, nutritional history, and blood studies
`were obtained.
`Outcomes
`Ellegård 1997
`Body weight was recorded each morning, in light clothing after
`voiding, but before breakfast, on statmos scale to the nearest 0.1
`Kg. Lean tissue mass, body fat, bone mineral content and bone
`mineral density were measured by dual energy x-ray absorptiome-
`try (DEXA). Energy content was determined by combustion in a
`bomb calorimeter; nitrogen in fecal samples and food duplicates
`was analysed by a modified Kjeldahl technique. Absorptive ca-
`pacity in percent was expressed as (1 - (excretion/intake)) × 100.
`Blood samples were analysed in one batch for insulin-like growth
`factor-1 (IGF-1) by radioimmunoassay.
`Scolapio 1997
`Body weight was recorded daily before breakfast.The patients wore
`light clothing. Lean body mass and percent body fats were mea-
`sured by dual energy x-ray absorptiometry (DEXA scan). Fecal
`nitrogen and fat were measured by macro-Kjeldahl method and
`the gravimetric technique. The percent of nutrient absorption was
`calculated by subtracting stool losses from enteral intake divided
`by the enteral intake and multiplied by 100. D-xylose was used
`to test intestinal carbohydrate malabsorption. Serum IGF-1 level
`was measured by radioimmunoassay.
`Szkudlarek 2000
`Jeppesen 2001) Weight was measured daily. The wet weight of the
`diet was calculated as the total weight of food and beverages, and
`ostomy output was calculated as the wet weight of faeces. Absorp-
`tion of wet weight was calculated as the difference between these
`two values. Intestinal absorption was calculated as the difference
`between oral intake and faecal loss. Energy was measured by two
`different methods: bomb calorimetry or by summarising the en-
`ergy values of carbohydrates, fat, and proteins (calculated on the
`assumption that all nitrogen originated from protein). Blood was
`obtained weekly for measurement of serum insulin-like growth
`factor 1 (IGF-1).
`Seguy 2003
`Body weight and height were recorded to the nearest 0.1 kg and
`0.5 cm, respectively. The oral metabolizable energy was calculated
`by subtracting the amount of energy excreted in stool output from
`that actually ingested, which corresponded to the difference be-
`tween control-duplicate meals and leftovers of served meals. Ni-
`trogen, fat and total energy content were determined by nitrogen
`elemental analysis using the method of van de Kamer and bomb
`calorimetry, respectively. Stool output was collected daily. Bioelec-
`tric impedance analysis was also performed to assess body compo-
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`Human growth hormone and glutamine for patients with short bowel syndrome (Review)
`Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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`sition. For the D-xylose test, fasted patients ingested 25 g D-xylose
`with 250 ml water and serum D-xylose level was determined after
`2 hours using a colorimetric method. Fasting blood samples were
`taken and serum was stored at -80°C to assess IGF-1.
`Byrne 2005
`The primary objective of this study was to evaluate the change in
`PN measured in week 2 (last week of baseline period) versus week
`6 (last week of treatment). The primary endpoint was PN volume;
`secondary endpoints were changes in PN calories and frequency of
`administration. A second objective was to evaluate the durability
`of any treatment effect over time. Thus, the endpoints measured
`
`on week 18 were compared with those variables at baseline. A third
`objective was to evaluate the safety of treatment.
`
`Risk of bias in included studies
`
`The Cochrane risk of bias tool indicates that the risk of bias was
`low for all of the 5 included studies (See Figure 1). All included
`studies were randomised controlled trials and all achieved adequate
`allocation concealment. All of the trials were double blind. All of
`the trials achieved complete follow up to their patients.
`
`Figure 1. Methodological quality summary: review authors’ judgements about each methodological quality
`item for each included study.
`
`Human growth hormone and glutamine for patients with short bowel syndrome (Review)
`Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
`
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`Effects of interventions
`
`Five studies met the inclusion criteria (Ellegård 1997; Scolapio
`1997; Seguy 2003; Szkudlarek 2000; Byrne 2005)and were in-
`cluded in the review. All studies included in this review except for
`Byrne 2005 were cross-over trials. Follmann’s technique was used
`for pooling data from cross-over studies.
`Primary outcome:
`
`Change in Body weight (Kg)
`Scolapio 1997 and Seguy 2003 reported a statistically signifi-
`cant change in body weight among the intervention group com-
`pared to placebo, while Szkudlarek 2000 did not find a significant
`
`change in weight comparing both arms. Ellegård 1997 reported
`results by comparing both arms to baseline. Byrne 2005 found
`that body weight decreased from pretreatment (screening) to end
`of follow-up, but there was no significant difference between treat-
`ment groups. Decreases in weight were correlated with pretreat-
`ment BMI (R = 0.5, P = 0.001) and the average body weights of
`the groups remained within 3% of ideal body weight. Data were
`pooled from 3 studies (Ellegård 1997;Seguy 2003; Szkudlarek
`2000) for the purpose of meta-analysis. The results of this meta-
`analysis showed a statistically significant effect of HGH with or
`without glutamine in increasing the body weight of these patients
`(MD 1.66 Kg, 95%CI 0.69 to 2.63; P = 0.0008; See Figure 2) at
`the end of therapy.
`
`Figure 2. Forest plot of comparison: 1 Comparison of growth hormone with or without glutamine versus
`placebo, outcome: 1.1 Change in weight (Kg).
`
`Secondary outcomes:
`1) Change in lean body mass
`Seguy 2003, Szkudlarek 2000 and Scolapio 1997 reported a sta-
`tistically significant increase in lean body mass (LBM) in the in-
`tervention group compared to placebo. Ellegård 1997 reported a
`statistically significant change in LBM the intervention arm com-
`pared to baseline. Pooled estimates were calculated for 3 studies
`and the results showed a statistically significant effect of HGH
`with or without glutamine in increasing LBM in comparison to
`placebo (MD 1.93 Kg; 95% CI 0.97 to 2.90; P = 0.0001; See
`Figure 3).
`
`Figure 3. Forest plot of comp