rHGH and Intestinal Permeability in Intestinal Failure

Short Bowel Syndrome Clinical Trial

— rHGH  

Official title:

Influence of Recombinant Human Growth Hormone on Intestinal Permeability and Liver Injury in Intestinal Failure Patients Receiving Parenteral Nutrition (Serono Project)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01380366
• Other study ID #: STU00012123 0208-007
• Secondary ID: CNV0050754
• Status: Completed
• Phase: Phase 4
• First received: June 22, 2011
• Last updated: January 12, 2016
• Start date: October 2006
• Est. completion date: February 2015

Study information

• Verified date: January 2016
• Source: Northwestern University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: February 2015
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Subjects must be between the ages of 18 and 80

• Subjects can be male or female

• Subjects must have short bowel syndrome with <200cm of functional small bowel or have severe small bowel dysfunction mandating regular (at least two times per week) administration of total parenteral nutrition (TPN) and/or IV fluids.

• Subjects must have been dependent on TPN or IV fluids for 1 year, or are expected to be dependent on TPN or IV fluids for at least 1 yr.

• Subjects must be patients being seen in the Northwestern intestinal failure clinic

• Subjects must be willing to spend one night in the Clinical Research Center

• Subjects must be able to read, understand and be able to sign the study specific informed consent

Exclusion Criteria:

• Subjects must be greater than or equal to 18 years of age, but less than or equal to 80 years of age

• Infections requiring antibiotic therapy within one week of starting the study

• Subjects must not have evidence of an ongoing malignancy for two years

• Subjects must not have history of antibiotic use within one week of initiating the study. Subjects may enroll in the study as long as Visit 1 is at least one week from the last dose of antibiotics.

• Subjects that have evidence of acute critical illness due to complications following open heart or abdominal surgery, multiple accidental trauma, or acute respiratory failure

• Subjects with known liver disease, positive hepatitis B virus (HBV), or hepatitis C virus (HCV) serology

• Subjects unwilling to abstain from alcohol 7 days prior to and during the 28 days of Zorbtive® therapy, until completion of Visit 2

• Subjects with a known sensitivity to Benzyl Alcohol

• Subjects with a known sensitivity to growth hormone

• Female subjects that are unable or unwilling to use effective, acceptable birth control methods throughout the study and for up to 6 months after completing treatment with Zorbtive therapy

• Female subject with a positive pregnancy test

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Short Bowel Syndrome

Intervention

Drug:
• Somatropin
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.

Procedure:
• Seven Day Food Diary
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 (standard of care)
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).

Other:
• Fasting
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.
• Sugar Permeability Test
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 Collection
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).

Locations

Country	Name	City	State
United States	Northwestern Memorial Hospital	Chicago	Illinois

Sponsors (3)

Lead Sponsor	Collaborator
Northwestern University	EMD Serono, Northwestern Memorial Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To Identify Small Intestinal Permeability Changes in Short Bowel Syndrome Patients After Administration of Recombinant Human Growth Hormone (Zorbtive®).	Permeability changes will be identified in short bowel syndrome patients by evaluating concentration of lactulose, mannitol and sucralose from Visit 1 to Visit 2. A decrease in concentration of sucralose in urine indicates Zorbtive potentially enhancing intestinal barrier function.	(Visit 1) Baseline to (Visit 2) 28-31 days after baseline	No
Secondary	To Evaluate Liver Enzymes in Total Parenteral Nutrition (TPN)-Dependent Short Bowel Syndrome Patients Before and After Administration of Zorbtive®.	Following completion of Visit 2, study staff will obtain results of liver injury/function tests (ALT, Aspartate transaminase (AST), bilirubin, alkaline phosphatase (ALK or ALP), GGT) from the medical record from each routine clinical exam from Month 3 through Month 24. Results that show decreased liver injury (ALT, AST, bilirubin, alkaline phosphate (ALK or ALP), GGT) will show Zorbtive administration enhanced intestinal permeability and enhanced liver function.	(Visit 1) Baseline, (Visit 2) 28-31 days after baseline, then at regularly scheduled follow-up clinic visits for two years from Month 3 through Month 24	No