Baby Observational and Nutritional Study

Study ID
BONUS-IP-11

Cancer Related
No

Healthy Volunteers
No

Study Sites

  • UT Southwestern-Other
  • Children’s Medical Center (Dallas, Plano, Southlake)

Contact
Andrew Hebert
214/456-7000
andrew.hebert@childrens.com

Principal Investigator
Preeti Sharma

Official Title

Baby Observational and Nutritional Study (BONUS)

Brief Overview


Cystic fibrosis (CF) is a life-shortening disease that causes breathing and digestive
problems, but can now be diagnosed at the time of birth. Lung function is very hard to
measure in infants, but growth is not. In this study the investigators aim to define growth
in infants with CF in the first year of life with research quality precision and to
understand factors that interfere with good growth.

Pancreatic enzyme replacement therapy (PERT) will be also be studied in a subgroup of
infants. Two different doses of PERT will be evaluated for improving fat and nitrogen
absorption in infants with CF.

Summary


Newborn screening (NBS) for cystic fibrosis (CF) has decreased the prevalence of
malnutrition in infancy, but suboptimal nutrition still persists. In one study, 60% of
infants diagnosed by NBS achieved their birth weight percentile by two years of age, while
40% did not. The many factors that contribute to this poor growth have not been defined and
persist despite pancreatic enzyme supplementation. Although published guidelines for the
clinical management of infants with cystic fibrosis in the U.S. and Europe exist, there is
an alarming scarcity of evidence to dictate care. In order to proceed with large scale
randomized studies to evaluate the range of interventions for infants with CF, we need to
not only develop precise techniques for measuring growth but also pursue unexplored factors
that may contribute to poor growth.

Enzyme therapy is a critical aspect of clinical management of nutrition and digestion in the
CF population. NBS has been implemented throughout the US, but there are no published
studies to guide dosing in infants. In addition to observing factors influencing growth, two
different doses of pancreatic enzyme replacement therapy (PERT) will be evaluated utilizing
the currently accepted measure of fat absorption, coefficient of fat absorption (CFA) in a
subgroup of infants using a crossover design.

This is a multi-center observational clinical study with a nested interventional PERT
sub-study. The observational study is designed to follow in a prospective manner incident
cases of CF for up to 12 months. The PERT sub-study is a randomized, double-blind, crossover
sub-study designed to evaluate the efficacy and safety of two doses of PERT (pancreatic
enzyme replacement therapy) for improving coefficient of fat absorption (CFA) in the stool
of infants with CF. All subjects will be enrolled in the observational study (a cohort of
approximately 225 subjects) and a subset of the observational study subjects will also be
enrolled in the PERT sub-study (approximately 24 subjects) at selected sites.

Participant Eligibility


Observational Study

Inclusion Criteria:

1. Signed informed consent

2. Males or females no more than three and one half (3.5) months of age at enrollment

3. Documentation of a CF diagnosis as evidenced by:

1. One or more of the following: one or more clinical features consistent with the
CF phenotype OR a positive newborn screening (NBS) OR a positive pre-natal
screen

AND

2. One or more of the following: sweat chloride ≥ 60 mEq/liter by quantitative
pilocarpine iontophoresis test (QPIT) OR two well-characterized mutations in the
cystic fibrosis transmembrane conductance regulator (CFTR) gene

4. Enrolled in the Cystic Fibrosis Foundation Patient Registry. (Patients may enroll in
the Registry at Enrollment Visit if not previously enrolled.)

Exclusion Criteria:

1. Children unable to take full oral feeds

2. Any serious or active medical condition, which in the opinion of the investigator,
contributes to malabsorption, interferes with normal growth, or would otherwise
interfere with subject's treatment, assessment, or compliance with the protocol.

3. Gestational age less than 35 weeks and/or birth weight < 2.5 kg.

PERT sub-study

Inclusion Criteria:

1. Currently enrolled in parent study (Observational study).

2. Written informed consent for PERT sub-study prior to any study related procedures.

3. Formula fed infants ≥ two (2) months of age but no more than five and one half (5.5)
months of age at PERT sub-study enrollment (Visit A).

4. Spot fecal elastase-1 (FE-1) ≤ 50 micrograms/g stool prior to Visit A.

5. Stable use of PERT at screening (any dose level that has not changed more than 1000
lipase units/kg/meal in seven (7) days prior to enrollment) or no prior pancreatic
enzyme replacement therapy.

Exclusion Criteria:

1. Unwilling or unable to remain on a stable caloric-density, cow or soy based formula
during the PERT sub-study.

2. Unwilling or unable to forgo breastfeeding and/or hydrolyzed or elemental formula
(e.g., Pregestimil, Alimentum, Nutramigen, Peptamen) during the PERT sub-study.

3. Weight for length (WFL) by WHO infant standards < 10th percentile at enrollment.

4. Weight less than five (5) kilograms at the time of PERT substudy enrollment.

5. Initiation of or dose change of Proton Pump Inhibitor (PPI) or other anti-acid
medications within the last seven (7) days.

6. Use of any systemic (oral or IV) antibiotics within the last (7) days.

7. Concurrent enrollment of a twin sibling in this study.