Subjects are initially evaluated in a screening visit (Day -3) during which they will be screened for eligibility, including baseline clinical and physical assessments (
Fig 1). At screening, the investigator or designee will review the subject’s medical history to determine eligibility, explain the study to the subject and the subject’s parent or legal guardian, and if eligible, obtain informed consent (
S3 File). Informed consent and assent will be obtained from study investigators and authorized personnel and the discussion will be documented in the patient’s electronic medical record. If consent is given and the subject is deemed eligible based on the results of the screening visit, they will be enrolled in the study and pre-baseline assessments will be performed, which will include physical examination, nutritional assessment, vital signs, and laboratory evaluations (
Fig 1). The subject’s parent or guardian will also receive education from a registered dietitian on recording caloric intake and composition in oral and enteral feeds, and PN. As part of this education, the dietitian will review how to record daily oral and enteral intake via paper dairy or with a HIPAA-compliant nutrition/food tracking phone application. If the latter, the subject’s parent or guardian will receive access to a nutrition/food tracking phone application.
The subject’s parent or guardian will then be asked to collect all stool for 72-hours over Day -3 to Day -1 and to record caloric intake and composition in oral and enteral feeds, and PN during that time. The collected stool will be submitted to the Boston Children’s clinical laboratory for total fat quantification. To evaluate the degree of fat malabsorption, the intake data and stool fat quantification will be used to measure the baseline CFA, as previously described [15 (
link)].
Treatment will be administered on study Day 1, followed by daily use of the RELiZORB enzyme cartridge whenever EN is administered, for a total of 90 days. During the treatment period, all EN will be administered through the RELiZORB enzyme cartridge. Nutritional intake (24-hour enteral dietary and PN volume intake), stool consistency/amount/frequency (if applicable) or ostomy (if applicable) output, study device use, and incidence of symptom changes will be recorded daily, in an electronic or paper diary, by the subject’s parent or guardian. Access to the nutrition/food tracking phone application along with a daily phone call from a study coordinator will be used to ensure accurate recording and completion of these tasks.
Subjects will return to the clinic on Days 7, 14, 28, 60, and 90 of the treatment period (
Fig 1). The final clinic visit will be preceded by a repeat 72-hour stool collection and measurement of CFA to determine the change (if any) in intestinal fat absorption. During the clinic visits, staff will review the information in the subject’s diary, review compliance with the use of the study device and discuss relevant observations with the subject during the visit. Upon review, information contained in the diary will be entered in the electronic database. In addition to a daily study coordinator phone call, the study staff will have weekly telephone contact with families during interim weeks after the day 14 visit. Prior to these visits, subjects will be weighed at home by their parent or guardian using a standardized weight scale. At the in-person clinic and weekly telephone visits, study staff will monitor safety, diaries, weight data, stool composition (Bristol scale) and output, changes in caloric intake, changes in urine output, and will make adjustments to PN and enteral feeding accordingly (
Fig 2). Adjustments will be based on the subject’s nutritional needs, weekly weights, height, hydration status and investigator’s medical judgement. If necessary, unscheduled visits can be arranged in place of the telephone contacts.
At each clinic visit, vital signs, physical examination, clinical evaluations, AEs, concomitant medications, medical/surgical procedures, and blood tests to determine the levels of liver enzymes will also be performed. Blood samples will be collected to analyze lipid profiles. All AEs post-baseline that occur will be recorded. Participants will meet with a study dietitian during each visit to assess nutritional needs and address issues or concerns.
Tsikis S.T., Fligor S.C., Mitchell P.D., Hirsch T.I., Carbeau S., First E., Loring G., Rudie C., Freedman S.D., Martin C.R., Gura K.M, & Puder M. (2023). Fat digestion using RELiZORB in children with short bowel syndrome who are dependent on parenteral nutrition: Protocol for a 90-day, phase 3, open labeled study. PLOS ONE, 18(3), e0282248.
