Clinical trial NCT00742157: Evaluate the Efficacy and Safety Growth Hormone, Glutamine and Diet in Patients With Short Bowel Syndrome (SBS)
Official title: An Open-label Evaluation of the Long-term Efficacy and Safety of a Standardized Regimen of Growth Hormone, Glutamine and a Modified Diet in the Treatment of Patients With Short Bowel Syndrome
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Short Bowel Syndrome
Keywords: Growth Hormone
TPN
Total Parenteral Nutrition
Glutamine
Short Bowel Syndrome
Increase in absorption of small bowel.
Lead sponsor: University of Nebraska
Sponsor class: OTHER
Collaborators: name: Eli Lilly and Company
First posted: 2008-08-27
Enrollment: 5
Sex: ALL
Minimum age (years): 19
Maximum age (years): 78
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Treatment for 3.5-8 weeks with GH (0.05 mg/kg/day) +GLN+Diet, followed by continued compliance to the individualized oral diet and enteral GLN, will result in reduced volume of TPN infusion/week and/or reduced frequency of TPN infusions/week.

Detailed description: Long-term total parenteral nutrition (TPN) is a supportive, rather than curative, therapy for patients with severe short bowel syndrome (SBS). Because of the complications (liver and kidney dysfunction, bone demineralization, nutrient deficiencies, catheter sepsis) and costs (\>$100,000/ patient/year) associated with this therapy, researchers have attempted to identify a safe, cost-effective alternative treatment modality. Various surgical procedures (including bowel transplantation) have been explored; however, these options currently offer limited clinical efficacy and significant morbidity and mortality. In contrast, a non-invasive therapy utilizing a growth factor (growth hormone - GH) and a bowel-specific nutrient (glutamine - GLN) in combination with an individualized oral diet (GH+GLN+Diet) has recently been shown to significantly enhance nutrient absorption and eliminate or reduce TPN requirements in patients with severe SBS.

This open-labeled, single-center trial with a total enrollment of 30 patients with severe SBS will examine the safety and effectiveness of a lower dose (0.05 mg/kg/day) of growth hormone. Thirty-two subjects have previously been studied at the Nutritional Restart Center in Massachusetts utilizing a higher dose (0.1 mg/kg/day) of growth hormone and identical treatment parameters as described in this protocol. The University of Nebraska Medical Center and the Nutritional Restart Center have agreed to pool the data from both studies and analyze the data according to the same primary efficacy variable. Subjects recruited to the lower-dose growth hormone group will be matched, using specific clinical criteria, to patients in the higher dose growth hormone group. The primary efficacy variable will be the change in volume of TPN infusion/week and frequency of TPN infusions/week at 6 months following discharge compared to baseline.

After a 3 day, baseline evaluation at The Nebraska Medical Center to determine pre-treatment TPN requirements and to assess the specific indices of nutritional and hydration status and kidney and liver function, and physical functioning capacity, patients will begin to receive lower dose GH (0.05 mg/kg/day) in combination with GLN (30 grams/day, orally) and the individualized oral/enteral diet. Treatment will last for a minimum of 23 days and a maximum of 54 days. Duration of treatment will be tailored to the patients' individual needs (e.g., understanding and acceptance of the modified diet, successful weaning of TPN). Patients may return to their home to continue receiving the GH treatment, provided they are tolerating the GH injections and understand how to properly administer the injections.

Eligibility criteria: Inclusion Criteria:

* Be male or female between 19 and 78 years of age, inclusive
* Have a diagnosis of SBS and 1 or more of the following characteristics:
* Dependent upon TPN and/or IV fluids
* Unable to receive TPN because of a documented history of complications associated with the long-term parenteral infusions (e.g. lack of venous access, multiple septic events, progressive liver dysfunction while on TPN, etc)
* A documented remnant bowel anatomy that is inconsistent with adequately supporting life without parenteral support (e.g. \< 70 cm of healthy small intestine and a portion of colon, or less than 150 cm in patients with no colon)
* A documented history of diarrhea and/or malabsorption that has significantly compromised the patient's nutritional and hydration status (e.g. significant weight loss - 5% over 1 month or 10% over 6 months, or a serum albumin \< 3.5 g/dl, documented nutrient deficiencies, documented episodes of dehydration, etc).
* Is able to eat at least some (\>500 calories) of solid food on a regular basis or tolerate at least some (\>500 calories) of an enteral feeding formula
* Have stable liver and renal function
* For patients with known hypertension and other cardiovascular disorders, be both compensated and stabilized on a regular therapeutic regimen
* For women participating in the study, manifest or give assent to 1 of the following criteria to ensure that the patient does not become pregnant during the study:
* The patient must be surgically sterile or demonstrably postmenopausal.
* Any patient capable of becoming pregnant must have a negative urine pregnancy test and must agree to practice a method of contraception documented to have at least 90% reliability throughout the treatment period.
* Have the ability to understand the requirements of the study, to provide written Informed Consent, and to abide by the study restrictions and agree to complete the required assessments in the Follow-up Period

Exclusion Criteria:

* Be pregnant or lactating
* Have a history of mental deficiency or illness that might compromise compliance with the requirements of the study
* Have clinically serious neurological dysfunction
* Have hypoxemic pulmonary diseases (i.e., resting pAO2 \< 75 torr)
* Have unstable ischemic heart disease or uncompensated cardiac failure
* Have participated in any study involving an investigations drug within 30 days prior to entry into this trial.

Primary outcomes:
measure: Documenting the Reduction of TPN Infusion/Week for Participants at 6 Months Compared to Baseline.
timeFrame: 6 months
Secondary outcomes:
measure: Change in Hydration Status
timeFrame: 6 months
measure: Change in Kidney Function at 6 Months Post Treatment
timeFrame: 6 months
measure: Change in Liver Function at 6 Months Post Treatment
timeFrame: 6 months
measure: Change in Physical Functioning Capacity at 6 Months Post Treatment as Compared to Baseline
timeFrame: 6 months
Other outcomes:
Locations:
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
Study officials:
affiliation: University of Nebraska
name: Fedja Rochling, MB, ChB
role: PRINCIPAL_INVESTIGATOR
References: