Baby Observational and Nutritional Study (BONUS)
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
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) |
- 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.
- 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 |
Observational Study
Inclusion Criteria:
- Signed informed consent
- Males or females no more than three and one half (3.5) months of age at enrollment
Documentation of a CF diagnosis as evidenced by:
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
- 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
- Enrolled in the Cystic Fibrosis Foundation Patient Registry. (Patients may enroll in the Registry at Enrollment Visit if not previously enrolled.)
Exclusion Criteria:
- Children unable to take full oral feeds
- 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.
- Gestational age less than 35 weeks and/or birth weight < 2.5 kg.
PERT sub-study
Inclusion Criteria:
- Currently enrolled in parent study (Observational study).
- Written informed consent for PERT sub-study prior to any study related procedures.
- 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).
- Spot fecal elastase-1 (FE-1) ≤ 50 micrograms/g stool prior to Visit A.
- 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:
- Unwilling or unable to remain on a stable caloric-density, cow or soy based formula during the PERT sub-study.
- Unwilling or unable to forgo breastfeeding and/or hydrolyzed or elemental formula (e.g., Pregestimil, Alimentum, Nutramigen, Peptamen) during the PERT sub-study.
- Weight for length (WFL) by WHO infant standards < 10th percentile at enrollment.
- Weight less than five (5) kilograms at the time of PERT substudy enrollment.
- Initiation of or dose change of Proton Pump Inhibitor (PPI) or other anti-acid medications within the last seven (7) days.
- Use of any systemic (oral or IV) antibiotics within the last (7) days.
- Concurrent enrollment of a twin sibling in this study.
Contacts and Locations| Contact: Jasna Hocevar-Trnka, MPH | 206-884-7527 | jasna.hocevar-trnka@seattlechildrens.org |
Show 27 Study Locations| 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: | Ramsey, Bonnie, MD |
| ClinicalTrials.gov Identifier: | NCT01424696 History of Changes |
| Other Study ID Numbers: | BONUS-IP-11 |
| Study First Received: | August 25, 2011 |
| Last Updated: | December 20, 2012 |
| Health Authority: | United States: Institutional Review Board United States: Food and Drug Administration |
Keywords provided by Ramsey, Bonnie, MD:
|
growth measures nutritional status pulmonary infection inflammatory markers pancreatic enzyme replacement therapy |
Additional relevant MeSH terms:
|
Infant, Newborn, Diseases Cystic Fibrosis Failure to Thrive Fibrosis Exocrine Pancreatic Insufficiency Pancreatic Diseases Digestive System Diseases Lung Diseases Respiratory Tract Diseases |
Genetic Diseases, Inborn Growth Disorders Pathologic Processes Pancrelipase Pancreatin Gastrointestinal Agents Therapeutic Uses Pharmacologic Actions |
ClinicalTrials.gov processed this record on June 18, 2013