Baby Observational and Nutritional Study (BONUS)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Seattle Children's Hospital
Sponsor:
Collaborator:
Cystic Fibrosis Foundation
Information provided by (Responsible Party):
Seattle Children's Hospital
ClinicalTrials.gov Identifier:
NCT01424696
First received: August 25, 2011
Last updated: April 23, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Cystic Fibrosis
Growth Failure
Exocrine Pancreatic Insufficiency
Drug: Pancrelipase 3000 USP units of lipase
Drug: Pancrelipase 750 USP units of lipase
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Baby Observational and Nutritional Study (BONUS)

Resource links provided by NLM:


Further study details as provided by Seattle Children's Hospital:

Primary Outcome Measures:
  • Incremental gain in weight, length, and head circumference [ Time Frame: one year ] [ Designated as safety issue: No ]
    To define and describe incremental weight gain and linear growth in the first year of life utilizing research quality growth measures that will be applicable as efficacy outcomes for future interventional studies in infants with CF

  • The period adjusted change in coefficient of fat absorption between two different doses of PERT [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    Treatment will consist of two-14 day consecutive treatment windows with 72 hour stool collections during the last 3 days of treatment.


Secondary Outcome Measures:
  • Nutritional, respiratory, and inflammatory factors that affect growth in patients with CF [ Time Frame: one year ] [ Designated as safety issue: No ]
    To explore, in a prospective manner, nutritional, respiratory, and inflammatory characteristics that may be associated with optimal or impaired incremental weight gain and linear growth

  • The period adjusted change in coefficient of nitrogen absorption between two different doses of PERT [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    Treatment will consist of two-14 day consecutive treatment windows with 72 hour stool collections during the last 3 days of treatment

  • Parent-reported outcomes [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    • Daily PERT use
    • Stool quality and number of stools per day
    • Parental perception of infant discomfort

  • Incidence of adverse events and serious adverse events [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
    • Frequency of AEs across different dose groups
    • Frequency of SAEs across different dose groups


Estimated Enrollment: 225
Study Start Date: December 2011
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: low dose phase
Pancrelipase 750 USP units of lipase, 500 lipase units/kg/meal
Drug: Pancrelipase 750 USP units of lipase
The contents of the capsule will be administered orally with a small amount of applesauce or other acidic food prior to each feeding.
Other Name: APT-1001
Active Comparator: high dose phase
Pancrelipase 3000 USP units of lipase, 2000 lipase units/kg/meal
Drug: Pancrelipase 3000 USP units of lipase
The contents of the capsule will be administered orally with a small amount of applesauce or other acidic food prior to each feeding.
Other Name: Zenpep

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   up to 3 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01424696

Contacts
Contact: Jasna Hocevar-Trnka, MPH 206-884-7527 jasna.hocevar-trnka@seattlechildrens.org

  Show 27 Study Locations
Sponsors and Collaborators
Seattle Children's Hospital
Cystic Fibrosis Foundation
Investigators
Principal Investigator: Drucy Borowitz, MD State University of New York at Buffalo
Principal Investigator: Daniel Leung, MD Baylor College of Medicine
Principal Investigator: James Heubi, MD University of Cincinnati
Principal Investigator: Daniel Gelfond, MD Women & Children's Hospital of Buffalo
  More Information

No publications provided

Responsible Party: Seattle Children's Hospital
ClinicalTrials.gov Identifier: NCT01424696     History of Changes
Other Study ID Numbers: BONUS-IP-11
Study First Received: August 25, 2011
Last Updated: April 23, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Seattle Children's Hospital:
growth measures
nutritional status
pulmonary infection
inflammatory markers
pancreatic enzyme replacement therapy

Additional relevant MeSH terms:
Infant, Newborn, Diseases
Cystic Fibrosis
Exocrine Pancreatic Insufficiency
Failure to Thrive
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Signs and Symptoms
Pancrelipase
Pancreatin
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 16, 2014