Energy Balance and Mechanisms of Weight Gain with Ivacaftor Treatment of Cystic Fibrosis Gating Mutations

Virginia A. Stallings; Nina Sainath; Megan Oberle; Chiara Bertolaso; Joan I. Schall

doi:10.1016/j.jpeds.2018.05.018

Energy Balance and Mechanisms of Weight Gain with Ivacaftor Treatment of Cystic Fibrosis Gating Mutations

Virginia A. Stallings, Nina Sainath, Megan Oberle, Chiara Bertolaso, Joan I. Schall

Research output: Contribution to journal › Article › peer-review

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Abstract

Objective: To determine if ivacaftor treatment results in weight gain and improved pulmonary function in people with cystic fibrosis transmembrane conductance regulator gating mutations. Study design: Children and adults with cystic fibrosis and at least 1 cystic fibrosis transmembrane conductance regulator gating mutation were evaluated in this observational study before and after 3 months of ivacaftor treatment. Body size and composition, total energy expenditure, resting energy expenditure (REE%) as percent predicted, coefficient of fat absorption (CFA%), fecal calprotectin, fecal elastase, and quality of life were assessed. Some outcomes were explored by pancreatic status. Results: There were 23 patients (5-61 years of age) who completed the study; 70% had pancreatic insufficiency (PI). Patients gained 2.5 ± 2.2 kg (P <.001) with increased (P <.05) fat-free mass (0.9 ± 1.9 kg) and fat mass (1.6 ± 1.5 kg). REE% decreased by 5.5 ± 12.0% (P <.05), fecal calprotectin decreased by 30 ± 40 µg/g stool (P <.01), and total energy expenditure was unchanged. Improvements were greater for PI than patients who were pancreatic-sufficient. CFA% increased significantly only with PI. The change (Δ) in weight was positively correlated with the percent change in forced expiratory volume at 1 second (r = 0.46; P =.028) and ΔCFA% (r = 0.47; P =.032) and negatively with ΔREE% (r = -0.50; P =.017). Together, ΔREE%, ΔCFA%, and the percent change in forced expiratory volume at 1 second explained 58% of the variance in weight gain (adjusted R ² = 0.579; P =.0007). Growth status and muscle strength improved, as did quality of life in several domains. Fecal elastase increased in most patients with pancreatic sufficiency, with no change in those with PI. Conclusions: Mechanisms identified for ivacaftor-associated weight gain were decreased REE, gut inflammation, and fat malabsorption (CFA). Trial registration: ClinicalTrials.gov: NCT02141464.

Original language	English (US)
Pages (from-to)	229-237.e4
Journal	Journal of Pediatrics
Volume	201
DOIs	https://doi.org/10.1016/j.jpeds.2018.05.018
State	Published - Oct 2018
Externally published	Yes

Bibliographical note

Funding Information:
Supported by Vertex Pharmaceuticals, Inc, The National Center for Advancing Translational Sciences, National Institutes of Health (UL1TR001878), the Clinical Translational Research Center (UL1RR024134, UL1TR000003), Nutrition Center, and the Cortner Endowed Chair (VAS) at Children's Hospital of Philadelphia. The study sponsor, Vertex Pharmaceuticals, Inc, had no involvement in the study design, the collection, analysis and interpretation of the data, the writing of the report, and the decision to submit the paper for publication. The malabsorption blood test patent invented by V.S. is held by Children's Hospital of Philadelphia and the test is not licensed commercially. All other authors declare no conflicts of interest.

Publisher Copyright:
© 2018 Elsevier Inc.

Keywords

cystic fibrosis
energy expenditure
fat absorption
gut inflammation

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title = "Energy Balance and Mechanisms of Weight Gain with Ivacaftor Treatment of Cystic Fibrosis Gating Mutations",

abstract = " Objective: To determine if ivacaftor treatment results in weight gain and improved pulmonary function in people with cystic fibrosis transmembrane conductance regulator gating mutations. Study design: Children and adults with cystic fibrosis and at least 1 cystic fibrosis transmembrane conductance regulator gating mutation were evaluated in this observational study before and after 3 months of ivacaftor treatment. Body size and composition, total energy expenditure, resting energy expenditure (REE%) as percent predicted, coefficient of fat absorption (CFA%), fecal calprotectin, fecal elastase, and quality of life were assessed. Some outcomes were explored by pancreatic status. Results: There were 23 patients (5-61 years of age) who completed the study; 70% had pancreatic insufficiency (PI). Patients gained 2.5 ± 2.2 kg (P <.001) with increased (P <.05) fat-free mass (0.9 ± 1.9 kg) and fat mass (1.6 ± 1.5 kg). REE% decreased by 5.5 ± 12.0% (P <.05), fecal calprotectin decreased by 30 ± 40 µg/g stool (P <.01), and total energy expenditure was unchanged. Improvements were greater for PI than patients who were pancreatic-sufficient. CFA% increased significantly only with PI. The change (Δ) in weight was positively correlated with the percent change in forced expiratory volume at 1 second (r = 0.46; P =.028) and ΔCFA% (r = 0.47; P =.032) and negatively with ΔREE% (r = -0.50; P =.017). Together, ΔREE%, ΔCFA%, and the percent change in forced expiratory volume at 1 second explained 58% of the variance in weight gain (adjusted R 2 = 0.579; P =.0007). Growth status and muscle strength improved, as did quality of life in several domains. Fecal elastase increased in most patients with pancreatic sufficiency, with no change in those with PI. Conclusions: Mechanisms identified for ivacaftor-associated weight gain were decreased REE, gut inflammation, and fat malabsorption (CFA). Trial registration: ClinicalTrials.gov: NCT02141464. ",

keywords = "cystic fibrosis, energy expenditure, fat absorption, gut inflammation",

author = "Stallings, {Virginia A.} and Nina Sainath and Megan Oberle and Chiara Bertolaso and Schall, {Joan I.}",

note = "Funding Information: Supported by Vertex Pharmaceuticals, Inc, The National Center for Advancing Translational Sciences, National Institutes of Health (UL1TR001878), the Clinical Translational Research Center (UL1RR024134, UL1TR000003), Nutrition Center, and the Cortner Endowed Chair (VAS) at Children's Hospital of Philadelphia. The study sponsor, Vertex Pharmaceuticals, Inc, had no involvement in the study design, the collection, analysis and interpretation of the data, the writing of the report, and the decision to submit the paper for publication. The malabsorption blood test patent invented by V.S. is held by Children's Hospital of Philadelphia and the test is not licensed commercially. All other authors declare no conflicts of interest. Publisher Copyright: {\textcopyright} 2018 Elsevier Inc.",

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T1 - Energy Balance and Mechanisms of Weight Gain with Ivacaftor Treatment of Cystic Fibrosis Gating Mutations

AU - Stallings, Virginia A.

AU - Sainath, Nina

AU - Oberle, Megan

AU - Bertolaso, Chiara

AU - Schall, Joan I.

N1 - Funding Information: Supported by Vertex Pharmaceuticals, Inc, The National Center for Advancing Translational Sciences, National Institutes of Health (UL1TR001878), the Clinical Translational Research Center (UL1RR024134, UL1TR000003), Nutrition Center, and the Cortner Endowed Chair (VAS) at Children's Hospital of Philadelphia. The study sponsor, Vertex Pharmaceuticals, Inc, had no involvement in the study design, the collection, analysis and interpretation of the data, the writing of the report, and the decision to submit the paper for publication. The malabsorption blood test patent invented by V.S. is held by Children's Hospital of Philadelphia and the test is not licensed commercially. All other authors declare no conflicts of interest. Publisher Copyright: © 2018 Elsevier Inc.

PY - 2018/10

Y1 - 2018/10

N2 - Objective: To determine if ivacaftor treatment results in weight gain and improved pulmonary function in people with cystic fibrosis transmembrane conductance regulator gating mutations. Study design: Children and adults with cystic fibrosis and at least 1 cystic fibrosis transmembrane conductance regulator gating mutation were evaluated in this observational study before and after 3 months of ivacaftor treatment. Body size and composition, total energy expenditure, resting energy expenditure (REE%) as percent predicted, coefficient of fat absorption (CFA%), fecal calprotectin, fecal elastase, and quality of life were assessed. Some outcomes were explored by pancreatic status. Results: There were 23 patients (5-61 years of age) who completed the study; 70% had pancreatic insufficiency (PI). Patients gained 2.5 ± 2.2 kg (P <.001) with increased (P <.05) fat-free mass (0.9 ± 1.9 kg) and fat mass (1.6 ± 1.5 kg). REE% decreased by 5.5 ± 12.0% (P <.05), fecal calprotectin decreased by 30 ± 40 µg/g stool (P <.01), and total energy expenditure was unchanged. Improvements were greater for PI than patients who were pancreatic-sufficient. CFA% increased significantly only with PI. The change (Δ) in weight was positively correlated with the percent change in forced expiratory volume at 1 second (r = 0.46; P =.028) and ΔCFA% (r = 0.47; P =.032) and negatively with ΔREE% (r = -0.50; P =.017). Together, ΔREE%, ΔCFA%, and the percent change in forced expiratory volume at 1 second explained 58% of the variance in weight gain (adjusted R 2 = 0.579; P =.0007). Growth status and muscle strength improved, as did quality of life in several domains. Fecal elastase increased in most patients with pancreatic sufficiency, with no change in those with PI. Conclusions: Mechanisms identified for ivacaftor-associated weight gain were decreased REE, gut inflammation, and fat malabsorption (CFA). Trial registration: ClinicalTrials.gov: NCT02141464.

AB - Objective: To determine if ivacaftor treatment results in weight gain and improved pulmonary function in people with cystic fibrosis transmembrane conductance regulator gating mutations. Study design: Children and adults with cystic fibrosis and at least 1 cystic fibrosis transmembrane conductance regulator gating mutation were evaluated in this observational study before and after 3 months of ivacaftor treatment. Body size and composition, total energy expenditure, resting energy expenditure (REE%) as percent predicted, coefficient of fat absorption (CFA%), fecal calprotectin, fecal elastase, and quality of life were assessed. Some outcomes were explored by pancreatic status. Results: There were 23 patients (5-61 years of age) who completed the study; 70% had pancreatic insufficiency (PI). Patients gained 2.5 ± 2.2 kg (P <.001) with increased (P <.05) fat-free mass (0.9 ± 1.9 kg) and fat mass (1.6 ± 1.5 kg). REE% decreased by 5.5 ± 12.0% (P <.05), fecal calprotectin decreased by 30 ± 40 µg/g stool (P <.01), and total energy expenditure was unchanged. Improvements were greater for PI than patients who were pancreatic-sufficient. CFA% increased significantly only with PI. The change (Δ) in weight was positively correlated with the percent change in forced expiratory volume at 1 second (r = 0.46; P =.028) and ΔCFA% (r = 0.47; P =.032) and negatively with ΔREE% (r = -0.50; P =.017). Together, ΔREE%, ΔCFA%, and the percent change in forced expiratory volume at 1 second explained 58% of the variance in weight gain (adjusted R 2 = 0.579; P =.0007). Growth status and muscle strength improved, as did quality of life in several domains. Fecal elastase increased in most patients with pancreatic sufficiency, with no change in those with PI. Conclusions: Mechanisms identified for ivacaftor-associated weight gain were decreased REE, gut inflammation, and fat malabsorption (CFA). Trial registration: ClinicalTrials.gov: NCT02141464.

KW - cystic fibrosis

KW - energy expenditure

KW - fat absorption

KW - gut inflammation

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Energy Balance and Mechanisms of Weight Gain with Ivacaftor Treatment of Cystic Fibrosis Gating Mutations

Abstract

Bibliographical note

Keywords

UN SDGs

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