rHGH and Intestinal Permeability in Intestinal Failure

NCT01380366 | Completed Phase 4 Results

• 2 other identifiers: STU00012123 0208-007CNV0050754
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Short Bowel Syndrome

Keywords

Malabsorption

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• To Evaluate Liver Enzymes in Total Parenteral Nutrition (TPN)-Dependent Short Bowel Syndrome Patients Before and After Administration of Zorbtive®.

  (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

Study Arms (1)

Patients consent to rHGH study

OTHER

Patients consent to be given growth hormone (rHGH) for their short bowel syndrome.

Drug: Somatropin; Procedure: Seven Day Food Diary; Procedure: Blood Tests (standard of care); Other: Fasting; Other: Sugar Permeability Test; Other: Urine Collection

Interventions

Somatropin DRUG

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.

Also known as: Recombinant human growth hormone (rHGH), Zorbtive®

Patients consent to rHGH study

Seven Day Food Diary PROCEDURE

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.

Patients consent to rHGH study

Blood Tests (standard of care) PROCEDURE

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).

Patients consent to rHGH study

Fasting OTHER

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.

Patients consent to rHGH study

Sugar Permeability Test OTHER

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.

Patients consent to rHGH study

Urine Collection OTHER

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).

Patients consent to rHGH study

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Northwestern University: lead
• Northwestern Memorial Hospital: collaborator
• EMD Serono: collaborator

Study Sites (1)

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

MeSH Terms

Conditions

Short Bowel Syndrome; Malabsorption Syndromes

Interventions

Human Growth Hormone; Growth Hormone; Diet Records; Hematologic Tests; Standard of Care; Angptl4 protein, mouse; Urine Specimen Collection

Condition Hierarchy (Ancestors)

Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Pituitary Hormones, Anterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Records; Organization and Administration; Health Services Administration; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Quality Indicators, Health Care; Quality of Health Care; Health Care Quality, Access, and Evaluation; Specimen Handling

Limitations and Caveats

Number of participants is low. Time period of evaluation may not have been adequate for evaluating the impact on liver injury. Parameters used to evaluate the impact of gut permeability changes on hepatic inflammation and injury were very limited.

Results Point of Contact

• Title: Dr. Jonathan Fryer, MD
• Organization: Northwestern University

jfryer@nmh.org

312-695-2125

Study Officials

• Jonathan Fryer, MD

  Northwestern Memorial Hospital, Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor in Surgery-Organ Transplantation

Study Record Dates

• First Submitted: June 22, 2011
• First Posted: June 27, 2011
• Study Start: October 1, 2006
• Primary Completion: February 1, 2011
• Study Completion: February 1, 2015
• Last Updated: February 8, 2016
• Results First Posted: March 31, 2014

Record last verified: 2016-01

Locations

US (1)