Current Environment:

Summary

Children with inadequate intestinal absorption due to loss of large amounts of small bowel require intravenous nutrition (feeding through the vein) to sustain hydration and nutrition to avoid starvation and dehydration; however, intravenous (IV) nutrition can lead to complications including liver failure. Tube feeding directly to the small intestine avoids the complications of IV nutrition, but fats are not fully digestible due to inadequate bowel function. We propose to predigest the fat using a small cartridge attached to the feeding tube to allow for rapid absorption with the possibility of reducing or eliminating the need for intravenous nutrition

Conditions

Short Bowel Syndrome, Malabsorption

Recruitment Status

Recruiting

Detailed Description

Project Summary/Abstract Short bowel syndrome (SBS) is often due to the loss of large amounts of small intestine that compromises digestive absorption. The treatments include (1) a high-calorie diet that includes vitamins, minerals, carbohydrates, proteins and fats; (2) injections of vitamins and minerals; (3) administration of drugs to slow the normal movement of the intestine or to increase the surface area of the intestinal lining; and (4) feeding through the vein (i.e., parenteral nutrition or PN). Many patients cannot wean from PN due to reduced intestinal length or function. Patients on long-term PN frequently experience serious metabolic complications, sepsis, hepatic biliary disorders including cholestasis, and fibrosis and can progress to liver failure. Full intestinal feeding (enteral nutrition) without PN is the optimal way to prevent the above complications. Enterally administered long chain triglycerides in patients with SBS, especially those with hepatic dysfunction, are not well tolerated due to bile acid malabsorption, which leads to decreased micelle formation and fat digestion. The dietary fat is unable to be emulsified by the bile acids and acted on by lipases before exiting the patient as stool. Switching to other forms of fat such as medium-chain triglycerides (MCTs) that do not require micelles for absorption may be better tolerated in patients with bile acid or pancreatic insufficiency but are not optimal as they increase the osmotic load in the intestine. This may increase the chance of stool dumping; moreover, MCTs do not contain essential fatty acids (FAs). The ability to provide the essential FAs such as those present in enteral formulas in a form that does not require the formation of micelles for absorption, would allow patients with SBS and those who are no longer PN dependent to receive adequate nutrition and continue to maintain the same growth trajectory as when they received the majority of their nutrition parenterally. RELiZORB is a digestive enzyme cartridge connected in-line with enteral feed tubing sets designed to mimic the function of pancreatic lipase. It is hypothesized that by using an external lipase device (RELiZORB) enteral nutrition will be better absorbed, and PN dependence reduced as enteral autonomy is increased. This product uniquely eliminates the need for intestinal emulsification and lipase activity and eliminates the risk of drugs, including lipases, allowing absorption at the time the diet enters the gut. The device has been shown to digest >90% of fat in most enteral formulas. This is a phase 4, open label single center clinical trial to determine the safety, tolerability, and bioavailability of the RELiZORB enzyme cartridge with enteral nutrition when used daily for 90 days in pediatric subjects with SBS, aged 5 years - 18 years, who are PN dependent. The change in PN calories from baseline, assessed at Day 7, 14, 28, 60, and 90, will be assessed by area under the curve and presented with a 95% confidence interval. The number (percent) of treatment-emergent adverse events, grade 2 or above, will be tabulated. Changes in growth, fecal fat/protein, plasma FAs, PN volume, and enteral/oral nutrition will be described.

Eligibility Criteria

Inclusion Criteria:

Male or female patients, aged 5 years - 18 years, inclusively.
Diagnosed with SBS, as determined by medical history or PN dependence (i.e. need for PN for >60 days after intestinal resection or a bowel length <25% of expected).
Congenital or acquired gastrointestinal disease requiring surgical intervention that has occurred at least 3 months prior to screening.
Subject is receiving no more than 40% calories from enteral fat.
At least 30% of daily caloric and fluid intake has been provided by PN for at least 6 months prior to screening.
Stable PN nutrition requirement, determined by less than 10% reduction in PN nutrition for at least 1 month prior to screening, or at the discretion of the investigator.
Screening direct bilirubin that is in the normal range for age and is not determined to be clinically significant by the investigator.
The patient has an existing feeding tube and is able to tolerate at least 20 ml/kg/day enteral nutrition.
The patient or a parent or legal guardian of the patient is able to read, understand, and is willing to provide informed consent (or assent, if applicable) for the patient.
The patient (if assent is applicable) or a parent or legal guardian is able to understand the requirements of the study and is willing to bring the patient to all clinic visits and complete all study related procedures (as determined by the investigator).
A parent or legal guardian is willing to provide written authorization for the use and disclosure of protected health information.

Exclusion Criteria:

Had a bowel lengthening procedure performed.
Other causes of chronic liver disease other than SBS (i.e. hepatitis C, cystic fibrosis, biliary atresia, alpha 1 anti-trypsin deficiency, and Alagille syndrome).
Any serum triglyceride concentration greater than 400 mg/dL at screening.
Pancreatic insufficiency as defined as the use of pancreatic enzymes within 30 days prior to screening.
Use of enteral bile salt sequestering agents (e.g., cholestyramine, colestipol, colesevelam) within 3 months prior to screening.
Evidence of untreated intestinal obstruction or active stenosis, as determined by the investigator.
Unstable absorption due to cystic fibrosis or known DNA abnormalities (i.e., familial adenomatous polyposis, Fanconi syndrome) as determined by the investigator.
History of microvillus inclusion disease, as determined by medical history.
Severe known dysmotility syndrome (i.e., pseudo-obstruction, gastroschisis-related motility disorders), as determined by the investigator.
Use of teduglutide growth hormone, or supplemental glutamine within 3 months prior to screening.
Active clinically significant pancreatic or biliary disease, as determined by the investigator.
Determined by the investigator to be unsuitable for participation in this trial for any reason.

Intervention

Intervention Type

Intervention Name

Device

Relizorb

Phase

Not Applicable

Gender

All

Minimum Age

5 Years

Maximum Age

18 Years

Download Date

November 23, 2021

Principal Investigator

Mark Puder

Primary Contact Information

Mark Puder, MD, PhD

617-355-1838

mark.puder@childrens.harvard.edu

For more information on this trial, visit clinicaltrials.gov.

Contact

For more information and to contact the study team: