rHGH and Intestinal Permeability in Intestinal Failure
Condition: Short Bowel Syndrome
MeSH terms: Short Bowel Syndrome; Intestinal Failure
Study type: Interventional
Phase: Phase 4

Summary: 
      Patients who are being asked to participate in this study have a short small bowel and will
      be prescribed to take the medication: Zorbtive® ("Zorbtive/Somatropin/(rHGH)"). Zorbtive® is
      an FDA approved recombinant human growth hormone (rHGH). The investigators want to see if
      taking this medication improves small bowel function by helping it to take in food,
      nutrients, vitamins and minerals. The investigators also believe that if the small bowel is
      absorbing food and nutrients better, liver function will improve as well. Therefore, liver
      function will also be monitored during the course of the study by performing blood tests.
    

Detailed description: 
      This is an open-label pilot study in which a convenience sample of 20 subjects will
      participate for up to 26 months.

      At the baseline visit, subjects will sign a consent form after all questions they have are
      answered. An inpatient appointment will be made at the General Clinical Research Center
      (GCRC). Subjects will be given instructions to fill out a 7-day food diary the week prior to
      their inpatient appointment. In this diary, subjects will be asked to record the types and
      amounts of food they ingest over a 7-day period. This will allow researchers to review
      subjects' food intake prior to sugar permeability testing. Although each subject serves as
      his/her own control, this information may be useful upon review of variations in permeability
      between subjects.

      To evaluate the potential hepato-protective effects of improving intestinal barrier function,
      blood tests evaluating liver injury and function (i.e. ALT, AST, total bilirubin, ALP, GGT)
      will be obtained. These labs are part of the subject's standard of care follow-up, therefore
      study staff will abstract these data from the subject's medical record. The sugar
      permeability testing requires an 8-hour overnight fast, followed by the ingestion of 4
      capsules of sucralose (250mg per capsule), 2.0 grams of mannitol, 7.5 grams of lactulose, and
      40 grams of sucrose in 150 mL of water. Over the next 5 hours, urine is collected. Intestinal
      permeability is quantified as the urine ratio of lactulose, mannitol and sucralose. After
      urine collection is complete, subjects will begin their 28 days of Zorbtive® administration.

      All evaluations (subject food diary, bloodwork, and sugar permeability testing) will be
      repeated 28 days later, within 72 hours of receiving the final dose of Zorbtive®. The
      bloodwork drawn is part of the subject's standard of care follow-up, therefore study staff
      will abstract these data from the subject's medical record.

      Following completion of study visits at the GCRC, study staff will obtain results of liver
      injury/ function tests [(ALT), (AST), bilirubin, alkaline phosphatase (ALK or ALP), (GGT)]
      from the medical record from each routine clinical exam from Month 3 through Month 24,
      following the 28-day treatment with Zorbtive® therapy. These labs are part of the subject's
      standard of care follow-up, therefore study staff will abstract these data from the subject's
      medical record. Subjects will not be asked to return for separate study visits.

      Since the intestinal epithelium is completely reconstituted approximately every 7 days, it is
      anticipated that the potential influences of rHGH on barrier function and related liver
      injury will be realized by the end of the 28 day study period. The long term durability of
      any changes observed after 28 days will be observed, but will likely require further study.
    

Intervention name(s): Somatropin; Seven Day Food Diary; Blood Tests (standard of care); Fasting; Sugar Permeability Test; Urine Collection
Intervention type(s): Drug; Procedure; Procedure; Other; Other; Other
Intervention description(s): Patients are given somatropin (growth hormone) for their short bowel syndrome for 28 days at a dose of 0.1 mg/kg subcutaneously daily to a maximum of 8 mg daily.; Subjects are asked to fill out a seven day food diary the week prior to their inpatient appointment, prior to receiving rHGH treatment for their short bowel syndrome. Subjects will be asked to repeat the use of a food diary after completing the administration of the growth hormone.; Blood tests are taken (standard of care) to evaluate the potential hepato-protective effects of improving intestinal barrier function on those receiving human growth hormone for short bowel syndrome. Per clinical protocol to test liver function i.e. Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline phosphatase (ALP), Gamma-glutamyl transpeptidase (GGT), Total Bilirubin). A complete blood count (CBC) with platelets (PLTS) and white-count differential (WBC with diff) is performed to check for anemia and infection. These tests will be taken at baseline (before fasting) and repeated again on the 28th day (last dose) of the growth hormone. Blood is also taken at clinical visit over the next two years (approximately every two months).; Eight hour overnight fast prior to being given sucralose, mannitol, lactulose, and sucrose. This is done at baseline (day one) and repeated again after the last dose of growth hormone and prior to sugar permeability urine tests.; Subject will be given 4 capsules of sucralose (250mg per capsule), 2.0 grams of mannitol, 7.5 grams of lactulose, and 40 grams of sucrose in 150 mL of water. This will be given on the second day of the study after an 8-hour overnight fast and repeated within 72 hours of the last dose of growth hormone.; Urine will be collected for the following five hours after subject has been given combination of sucralose, mannitol, lactulose, and sucrose to complete the intestinal sugar permeability test looking at urine ratio of lactulose to mannitol (L/M ratio). Tests include urinalysis (UA) and a blood urea nitrogen (BUN)/creatinine (Cr).
Other intervention name(s): Recombinant human growth hormone (rHGH); Zorbtive®
Intervention MeSH terms: Hormones
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Malabsorption