Clinical trial NCT01424696: Baby Observational and Nutritional Study
Official title: Baby Observational and Nutritional Study (BONUS)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cystic Fibrosis
Growth Failure
Exocrine Pancreatic Insufficiency
Keywords: growth measures
nutritional status
pulmonary infection
inflammatory markers
pancreatic enzyme replacement therapy
Lead sponsor: Seattle Children's Hospital
Sponsor class: OTHER
Collaborators: name: Cystic Fibrosis Foundation
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2011-08-29
Enrollment: 231
Sex: ALL
Maximum age (years): 3
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Infants diagnosed with CF who attend regular clinic visits during the first year of life

Brief summary: 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.

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.

This is a multi-center observational clinical study with a nested interventional PERT sub-study. The observational study was 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. The PERT sub-study was unable to enroll and closed. No results available.

Eligibility 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.

Primary outcomes:
measure: Incremental gain in weight, length, and head circumference
timeFrame: one year
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Atlanta
country: United States
facility: Emory CF Center
state: Georgia
city: Chicago
country: United States
facility: Lurie Children's Hospital of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital for Children
state: Indiana
city: Iowa City
country: United States
facility: Iowa City University of Iowa
state: Iowa
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Grand Rapids
country: United States
facility: Helen DeVos Children's Hospital CF Care Center
state: Michigan
city: Minneapolis
country: United States
facility: Children's Hospitals and Clinics of Minnesota
state: Minnesota
city: St. Louis
country: United States
facility: Cardinal Glennon Children's Medical Center
state: Missouri
city: St. Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Buffalo
country: United States
facility: State University of New York at Buffalo
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt CF Center
state: Tennessee
city: Austin
country: United States
facility: Austin Children's Chest Associates
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center at Dallas
state: Texas
city: Fort Worth
country: United States
facility: Cook Children's Medical Center
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
Study officials:
affiliation: State University of New York at Buffalo
name: Drucy Borowitz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Baylor College of Medicine
name: Daniel Leung, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Cincinnati
name: James Heubi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Women & Children's Hospital of Buffalo
name: Daniel Gelfond, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sathe M, Huang R, Heltshe S, Eng A, Borenstein E, Miller SI, Hoffman L, Gelfond D, Leung DH, Borowitz D, Ramsey B, Freeman AJ. Gastrointestinal Factors Associated With Hospitalization in Infants With Cystic Fibrosis: Results From the Baby Observational and Nutrition Study. J Pediatr Gastroenterol Nutr. 2021 Sep 1;73(3):395-402. doi: 10.1097/MPG.0000000000003173.
citation: Goetz D, Kopp BT, Salvator A, Moore-Clingenpeel M, McCoy K, Leung DH, Kloster M, Ramsey BR, Heltshe SH, Borowitz D. Pulmonary findings in infants with cystic fibrosis during the first year of life: Results from the Baby Observational and Nutrition Study (BONUS) cohort study. Pediatr Pulmonol. 2019 May;54(5):581-586. doi: 10.1002/ppul.24261. Epub 2019 Jan 22.
citation: LeGrys VA, Moon TC, Laux J, Accurso F, Martiniano SA. A multicenter evaluation of sweat chloride concentration and variation in infants with cystic fibrosis. J Cyst Fibros. 2019 Mar;18(2):190-193. doi: 10.1016/j.jcf.2018.12.006. Epub 2018 Dec 21.
citation: Kopp BT, Joseloff E, Goetz D, Ingram B, Heltshe SL, Leung DH, Ramsey BW, McCoy K, Borowitz D. Urinary metabolomics reveals unique metabolic signatures in infants with cystic fibrosis. J Cyst Fibros. 2019 Jul;18(4):507-515. doi: 10.1016/j.jcf.2018.10.016. Epub 2018 Nov 23.
citation: Gelfond D, Heltshe SL, Skalland M, Heubi JE, Kloster M, Leung DH, Ramsey BW, Borowitz D; BONUS Study Investigators. Pancreatic Enzyme Replacement Therapy Use in Infants With Cystic Fibrosis Diagnosed by Newborn Screening. J Pediatr Gastroenterol Nutr. 2018 Apr;66(4):657-663. doi: 10.1097/MPG.0000000000001829.