Clinical trial NCT01380366: rHGH and Intestinal Permeability in Intestinal Failure
Official title: Influence of Recombinant Human Growth Hormone on Intestinal Permeability and Liver Injury in Intestinal Failure Patients Receiving Parenteral Nutrition (Serono Project)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Short Bowel Syndrome
Keywords: Malabsorption
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: Northwestern Memorial Hospital
name: EMD Serono
First posted: 2011-06-27
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: 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

Primary outcomes:
measure: To Identify Small Intestinal Permeability Changes in Short Bowel Syndrome Patients After Administration of Recombinant Human Growth Hormone (Zorbtive®).
timeFrame: (Visit 1) Baseline to (Visit 2) 28-31 days after baseline
Secondary outcomes:
measure: To Evaluate Liver Enzymes in Total Parenteral Nutrition (TPN)-Dependent Short Bowel Syndrome Patients Before and After Administration of Zorbtive®.
timeFrame: (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
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
Study officials:
affiliation: Northwestern Memorial Hospital, Northwestern University
name: Jonathan Fryer, MD
role: PRINCIPAL_INVESTIGATOR
References: