NCT03783286

Brief Summary

The purpose of this research study is to determine the effects of clinically prescribed ivacaftor treatment on 4-24 month old children with CF and gating mutations on sleeping energy expenditure, growth status and gut health and function.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
15

participants targeted

Target at below P25 for all trials

Timeline
Completed

Started Feb 2019

Typical duration for all trials

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 18, 2018

Completed
3 days until next milestone

First Posted

Study publicly available on registry

December 21, 2018

Completed
2 months until next milestone

Study Start

First participant enrolled

February 6, 2019

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 30, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 30, 2021

Completed
Last Updated

March 11, 2022

Status Verified

March 1, 2022

Enrollment Period

2.9 years

First QC Date

December 18, 2018

Last Update Submit

March 10, 2022

Conditions

Cystic Fibrosis

Keywords

CF transmembrane conductance regulatorCFTRGating Mutations

Outcome Measures

Primary Outcomes (2)

  • Sleeping Energy Expenditure

    Investigators will examine the effects of 12 weeks of Ivacaftor treatment on subject's SEE. Using indirect calorimetry, SEE will be assessed using a computerized metabolic cart Vmax ENCORE at each protocol visit while the child is asleep. SEE will be assessed in the morning if possible and careful note of previous feeding of the child, including the time of day, amount of food, and feeding interval prior to test

    12 Weeks

  • Anthropometric Assessment

    Investigators will examine the effects of 12 weeks of Ivacaftor treatment on subject's BMI. Investigators will compare the results to BMI Z scores over 12 weeks compared to baseline.

    12 Weeks

Secondary Outcomes (3)

  • Fecal Elastase I/Pancreatic Function

    12 Weeks

  • Fecal Calprotectin/Gut Inflammation

    12 Weeks

  • Plasma Total Fatty Acids:

    4 to 6 months

Other Outcomes (4)

  • Dietary Intake

    12 Weeks

  • Serum fat soluble vitamins A, D, E and K, bile acids, and serum calprotectin

    12 Weeks

  • Muscle/Fat Stores

    12 Weeks

  • +1 more other outcomes

Interventions

IvacaftorDRUG

Ivacaftor (Kalydeco®, Vertex Pharmaceuticals Inc.) was the first of a new class of drugs that improved CFTR gating dysfunction (2, 3, 4). For such mutations (G551D, G178R, S549N, S549R, G551S, G970R, G1244E, S1251N, S1255P, G1349D) that permit CFTR expression at the cell membrane but compromise its activity.

Also known as: Kalydeco

Eligibility Criteria

Age4 Months - 2 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)
Sampling MethodNon-Probability Sample
Study Population

4-24 month old subjects with a diagnosis of cystic fibrosis with at least one CFTR gating mutation of these ten (G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, G1439D, or R117H) approved for treatment in a usual state of good health with a clinical decision to start ivacaftor treatment.

You may qualify if:

  • Cystic fibrosis with at least one CFTR gating mutation (E56K, G178R, S549R, S977F, F1074L, 2789+5G→A,P67L, E193K, G551D, F1052V, D1152H, 3272-26A→G, R74W, L206W, G551S, K1060T, G1244E, 3849+10kbC→T, D110E, R347H, D579G, A1067T, S1251N, D110H, R352Q, 711+3A→G, G1069R, S1255P, R117C, A455E, E831X, R1070Q, D1270N, R117H, S549N, S945L, R1070W, G1349D) approved for treatment
  • Age: 4-24 months of age
  • In their usual state of good health
  • A clinical decision has been made for subject to begin ivacaftor treatment
  • Family committed to the 4 to 6 month study protocol with visits to CHOP that will last 2 or 3 days for the baseline visit (Visit 1) prior to ivacaftor and the 12 week visit (Visit 3) after clinically prescribed ivacaftor treatment has begun, and will last 2 days for the 6 week visit (Visit 2) after ivacaftor treatment has begun.

You may not qualify if:

  • On parenteral nutrition
  • Use of any medications which are as inhibitors or inducers of cytochrome P450 (CYP) 3A
  • Liver function tests elevated above 3x the reference range for age and sex
  • Other illness affecting growth or nutritional status
  • Other contraindications described for ivacaftor therapy

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19146, United States

Location

Related Publications (13)

  • Stallings VA, Sainath N, Oberle M, Bertolaso C, Schall JI. Energy Balance and Mechanisms of Weight Gain with Ivacaftor Treatment of Cystic Fibrosis Gating Mutations. J Pediatr. 2018 Oct;201:229-237.e4. doi: 10.1016/j.jpeds.2018.05.018. Epub 2018 Jul 18.

    PMID: 30029855BACKGROUND

  • Van Goor F, Hadida S, Grootenhuis PD, Burton B, Cao D, Neuberger T, Turnbull A, Singh A, Joubran J, Hazlewood A, Zhou J, McCartney J, Arumugam V, Decker C, Yang J, Young C, Olson ER, Wine JJ, Frizzell RA, Ashlock M, Negulescu P. Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770. Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18825-30. doi: 10.1073/pnas.0904709106. Epub 2009 Oct 21.

    PMID: 19846789BACKGROUND

  • Accurso FJ, Rowe SM, Clancy JP, Boyle MP, Dunitz JM, Durie PR, Sagel SD, Hornick DB, Konstan MW, Donaldson SH, Moss RB, Pilewski JM, Rubenstein RC, Uluer AZ, Aitken ML, Freedman SD, Rose LM, Mayer-Hamblett N, Dong Q, Zha J, Stone AJ, Olson ER, Ordonez CL, Campbell PW, Ashlock MA, Ramsey BW. Effect of VX-770 in persons with cystic fibrosis and the G551D-CFTR mutation. N Engl J Med. 2010 Nov 18;363(21):1991-2003. doi: 10.1056/NEJMoa0909825.

    PMID: 21083385BACKGROUND

  • Ramsey BW, Davies J, McElvaney NG, Tullis E, Bell SC, Drevinek P, Griese M, McKone EF, Wainwright CE, Konstan MW, Moss R, Ratjen F, Sermet-Gaudelus I, Rowe SM, Dong Q, Rodriguez S, Yen K, Ordonez C, Elborn JS; VX08-770-102 Study Group. A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N Engl J Med. 2011 Nov 3;365(18):1663-72. doi: 10.1056/NEJMoa1105185.

    PMID: 22047557BACKGROUND

  • Energy and protein requirements. Report of a joint FAO/WHO/UNU Expert Consultation. World Health Organ Tech Rep Ser. 1985;724:1-206. No abstract available.

    PMID: 3937340BACKGROUND

  • Schofield WN. Predicting basal metabolic rate, new standards and review of previous work. Hum Nutr Clin Nutr. 1985;39 Suppl 1:5-41.

    PMID: 4044297BACKGROUND

  • 7. World Health Organization. WHO Child Growth Standards: Length/height-for-age, weight-for-age, weight-for-length, weight-for-height, and body mass index-for-age. Geneva, Switzerland: WHO Press, World Health Organization; 2006.

    BACKGROUND

  • Borowitz D, Baker SS, Duffy L, Baker RD, Fitzpatrick L, Gyamfi J, Jarembek K. Use of fecal elastase-1 to classify pancreatic status in patients with cystic fibrosis. J Pediatr. 2004 Sep;145(3):322-6. doi: 10.1016/j.jpeds.2004.04.049.

    PMID: 15343184BACKGROUND

  • Borowitz D, Lin R, Baker SS. Comparison of monoclonal and polyclonal ELISAs for fecal elastase in patients with cystic fibrosis and pancreatic insufficiency. J Pediatr Gastroenterol Nutr. 2007 Feb;44(2):219-23. doi: 10.1097/MPG.0b013e31802c41de.

    PMID: 17255835BACKGROUND

  • O'Connor MG, Seegmiller A. The effects of ivacaftor on CF fatty acid metabolism: An analysis from the GOAL study. J Cyst Fibros. 2017 Jan;16(1):132-138. doi: 10.1016/j.jcf.2016.07.006. Epub 2016 Jul 26.

    PMID: 27473897BACKGROUND

  • 11. World Health Organization. WHO Child Growth Standards: Head circumference-for-age, arm circumference-for-age, triceps skinfold-for-age, and subscapular skinfold-for-age. Geneva, Switzerland: WHO Press, World Health Organization; 2007.

    BACKGROUND

  • 12. WHO Multicenter Growth Reference Study Group. WHO Child Growth Standards: Growth Velocity Based on Weight, Length and Head Circumference: Methods and Development. Geneva, Switzerland: WHO Press: World Health Organization; 2009.

    BACKGROUND

  • Tindall A, Bass R, Maqbool A, Stallings VA. Changes in nutrition and growth status in young children in the first 12 weeks of ivacaftor therapy. J Cyst Fibros. 2023 Nov;22(6):989-995. doi: 10.1016/j.jcf.2023.04.010. Epub 2023 Jul 10.

    PMID: 37438197DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood and stool collections

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

ivacaftor

Condition Hierarchy (Ancestors)

Pancreatic DiseasesDigestive System DiseasesLung DiseasesRespiratory Tract DiseasesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesInfant, Newborn, Diseases

Study Officials

  • Virginia Stallings, MD

    Children's Hospital of Philadelphia

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Director of Nutrition Center Children's Hospital of Philadelphia, Professor of Pediatrics, Perelman School of Medicine at the University of Pennsylvania

Study Record Dates

First Submitted

December 18, 2018

First Posted

December 21, 2018

Study Start

February 6, 2019

Primary Completion

December 30, 2021

Study Completion

December 30, 2021

Last Updated

March 11, 2022

Record last verified: 2022-03

Data Sharing

IPD Sharing
Will not share

Locations

US(1)