Functional Sucrase Deficiency in Short Bowel Syndrome Patients With Intestinal Failure
Phase: PHASE2
Conditions: Short Gut Syndrome
Sponsor: University of Miami

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Title page:
Protocol Title: Functional sucrase deficiency 
in short bowel syndrome patients with 
intestinal failure
eProst Number: 
20191253
Protocol Version Number: 2
Protocol Version Date: 
PI Name: 
NCT Number: 
2/6/2020 
Amanda Fifi, MD 
NCT04604275
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1) Protocol Title
Functional sucrase deficiency in short bowel syndrome patients with intestinal failure
2) Objectives
Primary Aim:
To determine if sucrase supplementation in intestinal failure resulting from short gut 
syndrome will improve carbohydrate malabsorption, reducing symptoms such as bloating, 
diarrhea and abdominal pain and thus improve patient’s ability to advance enteral nutrition 
in short gut syndrome patients.
Secondary aim:
To determine if reduced bowel mass/length that occurs in short gut syndrome results in 
decreased functional sucrase levels and thus disaccharide malabsorption causing symptoms 
such as bloating, diarrhea and abdominal pain and/or resulting in inability to advance enteral 
nutrition.
3) Background
Short gut syndrome patients have decreased production of disaccharidases, like sucrase, due 
to loss of enterocyte mass and thus these patients cannot digest sucrose fully.
The resulting maldigestion of sucrose causes abdominal distension, vomiting and diarrhea 
that limits the advancement of enteral nutrition in short gut syndrome patients with intestinal 
failure
The administration of exogenous sucrase will improve sucrose digestion and thus the 
advancement of enteral nutrition in short gut syndrome patients with intestinal failure.
Sucrose digestion:
Carbohydrates in the diet provide the major exogenous source for glucose, which is the 
primary energy source for cells. They account for 40-60% of the calories in the western diet 
and higher percentages in protein scarce diets.
Carbohydrates are hydrophilic and require a series of reactions to digest them to 
monosaccharides which are absorbed in the small intestine.  The goal of carbohydrate 
digestion is to break down all disaccharides and complex carbohydrates into 
monosaccharides for absorption, although not all are completely absorbed in the small 
intestine - disaccharides are digested by specific enzymes, disaccharidases, in the microvillus 
membrane brush border.  Disaccharidases are protected from proteolysis by glycosylation 
and are found in higher concentration in villus enterocytes of the proximal small bowel.  The 
jejunum is the middle portion (mid-gut) of the small intestine and is where most nutrient 
absorption occurs. Some products of digestion that are not absorbed by the jejunum may also 
be absorbed by the ileum as this area can adapt to compensate for many of the jejunal 
functions.
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Sucrase is the dissacharidase responsible for digestion of sucrose to fructose and glucose in 
the intestinal lumen.  Sucrose uptake is then regulated after hydrolysis, by the apical 
membrane uptake rate of fructose and glucose.  Carbohydrates not digested in the small 
intestine pass into the large intestine where they are digested by colonic bacteria. This results 
in the release of short chain fatty acids (SCFA) (propionate, butyrate and acetate) along with 
methane. The SCFA provide vital nutrition to colonocytes, but excess volumes induce 
diarrhea and abdominal cramping.  Disaccharide deficiency results in symptoms due to an 
increased osmotic load in the small intestine and frequently elevated short chain fatty acid 
(SCFA) production in the colon.
Short Bowel syndrome:
Short bowel syndrome occurs most commonly following resections of the terminal ileum 
(such as in Crohn's disease or post-radiation enteritis), massive intestinal resection of 
infarcted bowel (due to compromised blood supply) and gastric bypass surgery as a therapy 
for weight loss. Common pediatric causes of short bowel syndrome include resections after 
episodes of necrotizing enterocolitis and repair of a volvulus. In rare cases, infants are born 
with a short bowel, congenital short bowel syndrome.
Intestinal failure is a subset of patients that are dependent on parenteral nutrition for some or 
all of their nutrition and fluid needs. Intestinal Failure is generally categorized as occurring 
secondary to (1) short bowel syndrome, referring to the spectrum of malabsorption that 
occurs after reduction of mucosal surface area from congenital or acquired lesions; (2) 
dysmotility or (3) mucosal enteropathy. These patients are unable to utilize enteral nutrients 
to meet the demands required for normal growth and development.  Usually recurrent bouts 
of diarrhea, vomiting, abdominal distension and/or growth failure limit the advancement of 
enteral feeds.  Deprivation of enteral calories, often termed “gut rest” in patients failing 
enteral nutrition, causes atrophy of the intestinal mucosa, even in the presence of adequate 
PN support.  This may reduce the surface area of intestinal brush border and reduce the 
production of disaccharidases like sucrase and their release into the intestinal lumen for 
carbohydrate digestion.
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Figure 1: Intestinal digestion of macro and micronutrients
Table 1: SUCROSE IN FORMULA USED IN PEDIATRIC SHORT GUT SYNDROME
Short bowel syndrome has a reported 5-year mortality rate as high as 30%. The incidence of 
necrotizing enterocolitis (NEC) is increasing with increased survival of premature babies in 
neonatal intensive care units and it has been estimated that 12% of infants born weighing less 
than 1500g will develop NEC.  Approximately 25% of NEC survivors have some degree of 
SBS.  Updated medical management of these patients have improved survival in patients 
with SBS and at present, the 5-year survival rates from SBS in infancy and childhood range 
from 73% to 89%.  Increasing incidence of SBS and improving 5-year survival rates leads to 
increase likelihood of physicians encountering these patients at some point in their practice.  
The most significant sources of morbidity and mortality in children with SBS are blood 
stream infections and parenteral nutrition-associated liver disease.  Strategies that advance 
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enterally feeding thus eliminating need for parenteral nutrition and need for central venous 
catheters can significantly improve outcomes in short bowel population.
To my knowledge there have been no studies on disaccharidases in short bowel syndrome 
populations or the use of disaccharidase supplementation to improve carbohydrate digestion 
in these patients.
4) Inclusion and Exclusion Criteria*
Inclusion:

Short bowel syndrome, of all ages, with dependence on parental support to provide 
at least 50% of fluid or caloric needs. 

Must be on diet containing sucrose.

Must be willing and able to sign informed consent

Adult and Pediatric patients (all ages)
Exclusion:

No current IV antibiotic administration for confirmed bout of bacteremia.

Cannot be NPO

Any condition, disease, illness, or circumstance that in the investigator’s opinion puts 
the subject at any undue risk, prevents completion of the study, or interferes with 
analysis of the study results
5) Study Design
a) Overall Study Design (single arm, parallel, open label etc.)
Placebo controlled crossover trial.
b) Scientific rational for study design
Placebo-controlled design was chosen because when they are utilized with randomization, 
they allow for valid treatment group comparisons. The disadvantage of parallel designs is 
that they can require large sample sizes due to the existence of both within- and between-
subject variation. Cross over studies generally require fewer participants than parallel 
designs because each participant serves as his/her own control, thus eliminating inter-
participant variation. Secondly, researchers can study individual participant response to 
treatment and examine participant-by-treatment interactions. Lastly, study recruitment may 
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be enhanced as potential participants are aware that they will receive active treatment at 
some point during the study.
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c) End of study definition
End of study will occur once all participants have undergone both intervention and placebo 
arm of the study.  Each subject will be enrolled for study period of 9 weeks. 
6) Arms and Interventions
Study Arm Description
Patients meeting inclusion criteria will be enrolled in the study and will provide 
written consented in keeping with regulations of the IRB.
Once enrolled “subjects” will be observed for 1 week on their current care and we 
will record:
Record daily:
Stool frequency and consistency
Side effects on sucrase – blood sugar checks by finger stick and any new symptoms – 
nausea, heacache, etc
Emesis
Record weekly:
Ability to advance feeds
Abdominal circumference
Weight
Patient or parent perception of tolerance of feeds on sucrase by telephone questionnaire
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Study Intervention Description
Subjects will be administered sucraid (sucrase) daily as instructed and followed as above.
There will be a one week wash out period
During cross over subjects will be administered “placebo” daily as instructed and followed 
as above.
a) Intervention dosing and administration information
The recommended dosage is as follows: 1 mL (8,500 I.U.) (one full measuring scoop or 28 
drops) per meal or snack for patients up to 15 kg in body weight. 2 mL (17,000 I.U.) Dosage 
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is 1 or 2 mL (8,500 to 17,000 I.U.) taken orally or by g-tube with each meal or snack diluted 
in water, milk, or infant formula. Half of the dosage will be taken at the beginning of the 
meal or snack and the remainder be taken during the meal or snack.  The beverage or infant 
formula should be served cold or at room temperature. The beverage or infant formula 
should not be warmed or heated before or after addition of Sucraid because heating is likely 
to decrease potency.
b) Study Intervention Compliance
Patients will be called weekly for verification of compliance.  Most patients have home 
nursing so their home nursing records will be reviewed as well.  Finally patients will be 
asked to verify how much medication they have left at end of each week to assess 
compliance.
7) Procedures Involved
Patients meeting inclusion criteria will be enrolled in the study and will provide written 
consented in keeping with regulations of the IRB.
Once enrolled “subjects” will be observed for 1 week on their current care and we will record:
Record daily:
Stool frequency and consistency
Side effects on sucrase – blood sugar checks by finger stick and any new symptoms – 
nausea, headache, etc
Emesis
Record weekly:
Ability to advance feeds
Abdominal circumference
Weight
Patient or parent perception of tolerance of feeds on sucrase by telephone questionnaire
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In the treatment arm of the study, subjects we will give sucrase at standard dose, 1 mL (8,500 
I.U.) (one full measuring scoop or 28 drops) per meal or snack for patients up to 15 kg in 
body weight. 2 mL (17,000 I.U.), for a total of 4 weeks and follow patients recording stool 
frequency and consistency, emesis, weight, ability to advance enteral nutrition.  Possible 
adverse effects of sucrase administration will also be recorded in addition to parental or 
patient perception of tolerance of feeds while on sucrase.
Give sucrase by g-tube or orally for 4 weeks
Record daily:
Stool frequency and consistency
Side effects on sucrase – blood sugar checks by finger stick and any new symptoms – 
nausea, headache, etc
Emesis
Record weekly:
Ability to advance feeds
Abdominal circumference
Weight
Patient or parent perception of tolerance of feeds on sucrase by telephone questionnaire
ONE WEEK WASH OUT – no recordings
Give placebo by g-tube or orally for 4 weeks
Record daily:
Stool frequency and consistency
Side effects on sucrase – blood sugar checks by finger stick and any new symptoms – 
nausea, heacache, etc
Emesis
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Record weekly:
Ability to advance feeds
Abdominal circumference
Weight
Patient or parent perception of tolerance of feeds on sucrase by  telephone questionnaire
Possible additional tests:
Some patients will undergo blood test for genetic testing if available, those who have been 
scheduled for an endoscopy, for other medically indicated reasons as decided by the medical 
team, will have biopsies taken to rule out CSID.
Patients who consent to breath test for functional sucrase deficiency will have testing done.
Procedures:
SucraidTM (sucrase) administration:
Subject will be asked to take sucrase either orally or through g-tube with feeds daily and will be 
provided with this medication at no cost. Subjects will take sucrase or placebo each for 4 weeks 
so they will be taking additional medication daily for 8 weeks as they participate in the study.
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Sucrose breath test:
This is an optional test for children over 4 years old that can cooperate by drinking a solution 
containing sucrose (sugar water) and breathing into a device to record components of their breath. 
The test will be offered free of charge to subjects in the study. This test is performed at home and 
the kit can be mailed back to us. The mailing costs are pre-paid. Inability to perform breath test 
will not eliminate subject from the study.
Endoscopy:
Endoscopies are often performed to assess patients with short bowel syndrome with intestinal 
failure who are not progressing as expected. They are done to check for many things, such as, 
bacterial overgrowth in the intestine, inflammation in the intestine, loss of intestinal cell function, 
infections in the intestines etc. If a subject has had an endoscopy (obtained for clinical reasons), 
we will ONLY access these results for research purpose. If subject has not had an endoscopy one 
will only be performed if clinically indicated by medical team – we will not take additional biopsies 
or ask for additional tests at the time of endoscopy.
Telephone surveys:
We will conduct short telephone surveys of subject’s symptoms while participating in the study. 
This would be similar to the phone calls they receive from the intestinal rehabilitation team about 
their feeds, stools, and other associated symptoms.
Medical chart review:
We will also look at recent growth chart in medical record to check growth before and during
the study period, we will ask the parent or home nurse to measure abdominal circumference,
weight and to check subject’s blood sugars at home.
8) Outcome measures
Primary outcomes:

Outcome Measure Title: Change in Carbohydrate Malabsorption
Outcome Measure Description:  Degree of carbohydrate malabsorption will be 
assessed by decrease in number of stools per day.
Outcome Measure Timeframe:  Baseline to Week 9

Outcome Measure Title: Change in Carbohydrate Malabsorption
Outcome Measure Description:  Degree of carbohydrate malabsorption will be 
assessed by change in patient symptomatology by change in score on patient 
symptom survey.
Outcome Measure Timeframe:  Baseline to Week 9

Outcome Measure Title: Change in Carbohydrate Malabsorption
Outcome Measure Description:  Carbohydrate malabsorption will be measured by 
increase in growth velocity in kg/week
Outcome Measure Timeframe:  Baseline to Week 9

Outcome Measure Title: Change in Carbohydrate Malabsorption
Outcome Measure Description:  Carbohydrate malabsorption will be measured by 
ability to advance enteral nutrition in ml/day
Outcome Measure Timeframe:  Baseline to Week 9
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Secondary outcomes

Outcome Measure Title: Improved Digestion
Outcome Measure Description:  Improved digestion will be measured by decreased 
abdominal distension/girth measured in cm
Outcome Measure Timeframe:  Baseline to Week 9

Outcome Measure Title: Improved Digestion
Outcome Measure Description:  Improved digestion will be assessed by number of 
emesis per day
Outcome Measure Timeframe:  Baseline to Week 9

Outcome Measure Title: Improved Digestion
Outcome Measure Description:  Improved digestion will be assessed by change in 
stool consistency from hard to formed to semi solid to liquid with pieces to only 
liquid observed daily
Outcome Measure Timeframe:  Baseline to Week 9
9) Adverse Events 
a) Definition of AEs
Reported adverse events are minor and rare with Sucraid (sucrase) and overdose has not 
been described.  In clinical studies the adverse experiences were as follows: abdominal 
pain, vomiting, nausea, diarrhea, constipation, insomnia, headache, nervousness, and 
dehydration.
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b) Definition of SAEs
In one study, one asthmatic child experienced a serious hypersensitivity reaction 
(wheezing) probably related to sacrosidase. The event resulted in withdrawal of the patient 
from the trial but resolved with no sequelae.
c) Time Period and Frequency for AE assessment and Follow-up
During weekly phone calls we will assess for worsening symptoms, including but not 
limited to the AE as listed above
d) Adverse Event Reporting
All adverse events as defined by the FDA will be recorded by study team and reported in 
the results section of the study and publications.
e) Serious Adverse Event Reporting
All adverse events as defined by the FDA will be recorded by study team and reported in 
the results section of the study and publications.  Subjects will be withdrawn as necessary 
if SAE occurs during study period.
10) Data and Specimen Banking
Data will be kept on a secure drive and only be accessed by the study team members.  Data 
will be de-identified prior to data entry.
Specimens taken for pathology (for other medically indicated reasons) will be kept in patients 
private medical record as usual.
11) Data Management
Statistics will be done in compliance with HIPAA regulations on de-identified data.
Data will be stored on a secure drive and only accessible to study team members during and 
after the study.
Data will be kept post collection in compliance with regulations.
  
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12) Risks to Subjects
Sucrase may cause a serious allergic reaction. 
Blood glucose levels may change after taking sucrase – each patient already has monitor to 
check daily sugars while on therapy.
Some patients treated with sucrase may have worse abdominal pain, vomiting, nausea, or 
diarrhea. Constipation, difficulty sleeping, headache, nervousness, and dehydration have also 
occurred in patients treated with sucrase. 
Patients will only undergo endoscopy with biopsy if there is another medical indication as 
decided by the primary medical team (not the study team).  Thus this risk does not pertain to 
the study. 
13) Potential Benefits to Subjects
The most significant sources of morbidity and mortality in children with SBS are catheter 
related blood stream infections and parenteral nutrition-associated liver disease.  Strategies 
that advance enterally feeding thus eliminating need for parenteral nutrition and thus central 
venous catheters can significantly improve outcomes in short bowel population.
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14) Participant Discontinuation/ Withdrawal from the study
Participants may be discontinued if:

They have bacteremia during course of study period and require IV antibiotic 
administration.

They experience SAE or an AE that prevents them from continuing medication.

They are admitted to the icu or hospital and made NPO during study period

They undergo an unplanned surgery or procedure requiring them to be NPO for 
more than 12 hours

They are switched by medical team to a diet not containing sucrose.

They are no longer willing to participate in study
We will attempt to replace the withdrawn participant with another subject.
Any data collected on withdrawn subjects will be removed for purposes of statistical 
analysis.
15) Vulnerable Populations
 NIL
16) Setting
Jackson Memorial Health system/University of Miami
17) Resources Available
Amanda Fifi, Assistant Professor of Pediatrics, Pediatric GI and Nutrition Specialist who 
runs the nutrition program at UM and Jackson that treats many patients with SBS.  She has 
published articles on topic of SBS. 
Jenn Garcia, Assistant Professor of Pediatrics, Pediatric GI and Short Bowel Syndrome 
Specialist who heads the Intestinal Rehabilitation and Intestinal Transplant service at 
Jackson and UM.  She has published and presented data related to care of SBS for several 
years in many international meetings.
Miguel Saps, Professor of Pediatrics, Division Chief of Department of Pediatric GI, well-
published, world-renowned Pediatric GI specialist and also prior consultant on use of 
sucrase in patients with sucrase deficiency.
18) Prior Approvals
NIL
19) Recruitment Methods
We will obtain approval through the institutional review board (IRB)  at University of Miami 
and Jackson Health system.  We will recruit patients, both adult and pediatric, through our 
Intestinal Rehabilitation Program at their regular clinic appointments in conjunction with the 
medical team.  SGS is a rare disease and the list of patients with this condition that may meet 
criteria for this study is short.  They will be approached in clinic by the primary medical team 
who follow these patients regularly. Patients will be consented in keeping with regulations of 
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the IRB.  Only after recruitment and consent to participate in study will study access the 
medical records of the patients with their consent.
20) Local Number of Subjects
10 subjects
21) Confidentiality
Data, documents, reports, scans, specimens, etc. (not including consent documents) will be 
kept locally in a manner that is :
☐  Identifiable – provides least amount of protection
☒  De-identified and coded with the link between code and subject’s identity maintained 
separately from the data. 
☐  De-identified with no link to subject’s identity
How will specimens obtained for this research be maintained? 
☐  Identifiable – provides least amount of protection
☒  De-identified and coded with the link between code and subject’s identity maintained 
separately from the data. 
☐  De-identified with no link to subject’s identity
If data or specimens will be coded, who will have access to the code sheet?
☒  Principal Investigator at UM/JHS
☐  Sponsor/funding entity
☐  Other, specify:  
Data will be collected and stored on UM redcap and One Drive and will be password 
protected with password only known to specific members of the study team.
Paper Records (e.g., consent forms, data files, medical records, etc.): Paper files related to 
human subjects participation in research will be securely stored on campus. Access to files 
will be restricted to key personnel and supervised by the principal investigator(s) of the 
study. They will be kept in a secured office only accessible to PI.  
Digital Records (e.g., electronic files etc.): Digital files containing human subjects research 
data will be stored in password protected files, on University maintained servers with regular 
and secured back-up. Sensitive data will also be encrypted, stored, and securely erased when 
appropriate.
Only the study team will have access to data. 
Data will be de-identified and coded with the link between code and subject’s identity 
maintained separately from the data prior to data entry and statistical analysis.
We will destroy or de-identify the information we collect at the earliest opportunity.
The information we collect will not be reused or disclosed to any other person or entity, 
except as required by law, for authorized oversight of the research study or for other research 
for which the use or disclosure of PHI is permissible.
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22) Provisions to Protect the Privacy Interests of Subjects
Data will be stored on a zip drive that is password protected with password only known 
to specific members of the study team.
Only the study team will have access to data
Data will be deidentified prior to data entry and statistical analysis
23) Consent Process
Written consent will be obtained for all subjects >18 years old involved in the study.  One 
parent consent will be obtained for subjects <18 years old.  Additionally subject assent 
will be obtained for subjects 10-17 years old.
24) Process to Document Consent in Writing
As above.
25) References

Castillo RO1, Feng JJ, Stevenson DK, Kwong LK. Am J Clin Nutr. 1991 
Feb;53(2):558-61. Altered maturation of small intestinal function in the absence of 
intraluminal nutrients: rapid normalization with refeeding. 

E.J. Feldmanc R.H. Dowling J. McNaughton T.J. Peters. Effects of Oral Versus 
Intravenous Nutrition on Intestinal Adaptation After Small Bowel Resection in the Dog 
.

Kerri B. Gosselin, MD, MPH, Christopher Duggan, MD. Enteral Nutrition in the 
Management of Pediatric Intestinal Failure,.

Crenn P1, Messing B, Cynober L.  Citrulline as a biomarker of intestinal failure due to 
enterocyte mass reduction. 

Christine Waasdorp Hurtado, MD, MSCS, FAAP. Carbohydrate Digestion and 
Absorption NASPGHAN Physiology Series 

Khursheed N. Jeejeebhoy. Short bowel syndrome: a nutritional and medical approach. 

Schalamon J, Mayr JM, Hollwarth ME. Mortality and economics in short bowel 
syndrome. Best practice & research Clinical gastroenterology. 2003;17(6):931-42.

Gephart SM, McGrath JM, Effken JA, Halpern MD. Necrotizing enterocolitis risk: 
state of the science. Advances in neonatal care : official journal of the National 
Association of Neonatal Nurses. 2012;12(2):77-87; quiz 8-9.

Henry MC, Moss RL. Neonatal necrotizing enterocolitis. Seminars in pediatric surgery. 
2008;17(2):98-109.
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