SBS short bowel disease
Conditions
Interventions
All three groups will receive NTRA-9620 or matching placebo four times per day
for 24 weeks.
Group 1: NTRA-9620 2 IU/kg for each dose (8 IU/kg per day).
Group 2: NTRA-9620 1 IU/kg for each dose (4 IU
intestinal malabsoption
Short Bowel Syndrome
surgical resection of the intestine.
Sponsors
Nutrinia Ltd
Eligibility
Age
2 Years to 11 Years
Inclusion criteria
Inclusion criteria: Subjects must meet all of the following criteria to be included: 1) Subject must be at least 28 weeks post-menstrual age and up to 52 weeks chronological age at enrollment. 2) Subject weight must be at least 500 grams (17.6 ounces) at time of enrollment. 3) Clinically diagnosed with SBS requiring PN/IV secondary to surgical resection of the intestine. 4) After major surgical resection leading to SBS, the subject has maximally 70% of expected bowel length preserved or an ostomy in place such that * 70% of the small bowel is available for absorption . 5) Subject can tolerate at least 10 mL/kg/day of enteral nutrition (EN) for at least 7 days at time of enrollment. 6) At time of enrollment subject is on at least 70% of prescribed PN/IV and no more than 30% of EN based on total caloric intake for at least 7 days prior to study entry. 7) Subject is randomized into the trial within 4 months from the surgical resection that has led to the diagnosis of SBS. 8) Subject*s parent(s) or legal guardian(s) provide written informed consent. 9) Subject*s parent(s) or legal guardian(s) understand and are willing to comply with all study procedures and requirements.
Exclusion criteria
Exclusion criteria: Subjects meeting any of the following criteria at study entry will be excluded: 1) Subject has undergone any bowel lengthening procedure. 2) Subject has a malabsorption disorder such as: * Congenital etiology (such as microvilli inclusion disease, tufting enteropathy) * Untreated Hirchsprung*s disease 3) Significant motility disorder such as: * Pseudo obstruction * Severe gastroschisis defined as: primary reason for PN support is due to persistent feeding intolerance of less than 20 ml/kg/day EN intake or signs and symptoms (i.e., abdominal distention, vomiting) requiring prokinetic agents. 4) Any known inherited abnormality (e.g., Fanconi syndrome,) that is not related to SBS. 5) Prior bowel resection due to isolated spontaneous intestinal perforation. 6)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoints are the percent changes in %PN (PC_PN0-t) from baseline based on caloric intake to 12 weeks and again to 24 weeks. Each endpoint is calculated as: *PC_PN*_(0-t)=100×(*%PN*_Baseline-*%PN*_t)/*%PN*_Baseline where: t = 12 or 24weeks. %PN = % Parenteral Nutrition (feeding) calculated as parenteral calories divided by calculated total caloric requirements (the Schofield equation ). Each *PC_PN*_(0-t) observation will be computed as an average over a single week. Thus, for example, PC_PN at 12 weeks will be the average of PC_PN over days 78 to 84. PC _PN at 24 weeks will be the average of PC_PN over days 162 to 168. The study will have shown benefit if either PC_PN0-12 or PC_PN0-24 in the treated group is statistically significantly superior to placebo. | — |
Secondary
| Measure | Time frame |
|---|---|
| Key Secondary Endpoint Time to reduction of PN to less than 10% of the total caloric intake on 14 consecutive days. Other Secondary Endpoints a) Time to wean off parenteral nutrition b) Number of patients reaching readiness to wean off at 12 and 24 weeks from baseline. c) Time to 50% PN/IV reduction from baseline in %PN based on total calories. d) Time to 50% PN/IV reduction from baseline in %PN based on volume. e) Number of patients reaching 50% PN/IV reduction from baseline in %PN based on total calories at 12 and 24 weeks. f) Number of patients reaching 50% PN/IV reduction from baseline in %PN based on volume at 12 and 24 weeks. g) Percent change from baseline in %PN/IV based on total calories. h) Percent change from baseline in %PN/IV based on volume. i) Percent change from baseline in PN/IV fluid volume during treatment period. j) Change in Z-scores (Fenton) from baseline during the treatment period k) Percent change from baseline in %EN based on total calories. l) Percent change from baseline in %EN based on total volume. m) Change from baseline in liver enzymes (ALT, GGT, and total and direct bilirubin). n) Change from baseline in plasma citrulline levels. o) Change from baseline in body weight during the treatment period. p) Weekly average of hours on prescribed PN/IV during the last month of treatment. q) General safety variables including episodes of significant feeding intolerance compared to placebo. | — |
Countries
The Netherlands
Outcome results
None listed