TY - JOUR
T1 - Sildenafil improves exercise capacity in patients with cystic fibrosis
T2 - a proof-of-concept clinical trial
AU - Rodriguez-Miguelez, Paula
AU - Ishii, Haruki
AU - Seigler, Nichole
AU - Crandall, Reva
AU - Thomas, Jeffrey
AU - Forseen, Caralee
AU - McKie, Kathleen T.
AU - Harris, Ryan A.
N1 - Funding Information:
The authors would like to thank all of the patients and patients? families for their commitment to this research investigation. Special acknowledgment goes to the Pediatric and Adult CF Center teams at Augusta University for assisting with patient recruitment. The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by National Institute of Health/National Institute of Diabetes and Digestive and Kidney Diseases (NIH/NIDDK R21DK100783, RAH).
Funding Information:
In conclusion, for the first time our data documents an improvement in exercise capacity following both an acute dose and 4 weeks of sildenafil treatment in patients with CF. Indeed, pulmonary function prior to treatment could play a role in the efficiency of sildenafil to improve exercise capacity in CF. The present findings support proof-of-concept for the use of sildenafil to improve exercise tolerance in CF. These results could possibly represent an initial therapeutic approach to improve exercise capacity in patients with CF with the use of an already FDA-approved treatment. Future studies are certainly needed to evaluate the most effective dose, duration, and impact of PDE5 inhibition to better understand the treatment efficacy on exercise capacity in CF. The authors would like to thank all of the patients and patients’ families for their commitment to this research investigation. Special acknowledgment goes to the Pediatric and Adult CF Center teams at Augusta University for assisting with patient recruitment. Funding The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by National Institute of Health/National Institute of Diabetes and Digestive and Kidney Diseases (NIH/NIDDK R21DK100783, RAH). Conflict of interest statement The authors declare that there is no conflict of interest. ORCID iDs Paula Rodriguez-Miguelez https://orcid.org/0000-0003-3582-4483 Ryan A. Harris https://orcid.org/0000-0002-8826-681X
Publisher Copyright:
© The Author(s), 2019.
PY - 2019
Y1 - 2019
N2 - Background: Exercise intolerance is a common phenotype observed in patients with cystic fibrosis (CF). Treatment with sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor, has previously been shown to improve exercise capacity (VO2 peak) in other patient populations. Thus, the present study sought to determine the acute and subacute effects of sildenafil on exercise capacity in patients with CF. Methods: The present investigation utilized a randomized, double-blind, placebo-controlled, crossover study with an acute dose of either sildenafil (50 mg) or placebo (n = 13, age 25 ± 10), followed by a 4 week open-label extension with sildenafil (20 mg, TID; n = 15, age 23 ± 11). A comprehensive evaluation of pulmonary function and a maximal exercise test were each performed at every visit. Results: A significant increase in VO2 peak was observed after the acute sildenafil dose with no changes following placebo (77 ± 13 versus 72 ± 13% predicted; p = 0.033). In addition, after 4 weeks of treatment, patients showed a significant increase in exercise capacity (72 ± 12 versus 75 ± 12% predicted; p = 0.028) and exercise duration (409 ± 98 versus 427 ± 101 s; p = 0.014). A robust correlation (r = 0.656; p = 0.008) between baseline FEV1 (% predicted) and the change in exercise capacity following 4 weeks of treatment was identified. Conclusions: This proof-of-concept clinical trial demonstrates that sildenafil treatment can improve exercise capacity in patients with CF and that pulmonary function may play an important role in the effectiveness of treatment. Future investigations of sildenafil treatment in patients with CF are certainly warranted.
AB - Background: Exercise intolerance is a common phenotype observed in patients with cystic fibrosis (CF). Treatment with sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor, has previously been shown to improve exercise capacity (VO2 peak) in other patient populations. Thus, the present study sought to determine the acute and subacute effects of sildenafil on exercise capacity in patients with CF. Methods: The present investigation utilized a randomized, double-blind, placebo-controlled, crossover study with an acute dose of either sildenafil (50 mg) or placebo (n = 13, age 25 ± 10), followed by a 4 week open-label extension with sildenafil (20 mg, TID; n = 15, age 23 ± 11). A comprehensive evaluation of pulmonary function and a maximal exercise test were each performed at every visit. Results: A significant increase in VO2 peak was observed after the acute sildenafil dose with no changes following placebo (77 ± 13 versus 72 ± 13% predicted; p = 0.033). In addition, after 4 weeks of treatment, patients showed a significant increase in exercise capacity (72 ± 12 versus 75 ± 12% predicted; p = 0.028) and exercise duration (409 ± 98 versus 427 ± 101 s; p = 0.014). A robust correlation (r = 0.656; p = 0.008) between baseline FEV1 (% predicted) and the change in exercise capacity following 4 weeks of treatment was identified. Conclusions: This proof-of-concept clinical trial demonstrates that sildenafil treatment can improve exercise capacity in patients with CF and that pulmonary function may play an important role in the effectiveness of treatment. Future investigations of sildenafil treatment in patients with CF are certainly warranted.
KW - PDE5 inhibitors
KW - clinical trial
KW - cystic fibrosis
KW - exercise intolerance
UR - http://www.scopus.com/inward/record.url?scp=85075506135&partnerID=8YFLogxK
U2 - 10.1177/2040622319887879
DO - 10.1177/2040622319887879
M3 - Article
AN - SCOPUS:85075506135
VL - 10
JO - Therapeutic Advances in Chronic Disease
JF - Therapeutic Advances in Chronic Disease
SN - 2040-6223
ER -