NCT02626182

Brief Summary

This study evaluates the ability of the drug sildenafil to improved exercise capacity, cardiac performance during exercise, and quality of life in patients with moderate to severe CF lung disease. 3/4 of the subjects will receive sildenafil and 1/4 will receive placebo.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
14

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Dec 2015

Typical duration for phase_1

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

Study Start

First participant enrolled

December 1, 2015

Completed
2 days until next milestone

First Submitted

Initial submission to the registry

December 3, 2015

Completed
7 days until next milestone

First Posted

Study publicly available on registry

December 10, 2015

Completed
2.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 18, 2018

Completed
11 days until next milestone

Study Completion

Last participant's last visit for all outcomes

January 29, 2018

Completed
1.5 years until next milestone

Results Posted

Study results publicly available

July 15, 2019

Completed
Last Updated

July 24, 2019

Status Verified

July 1, 2019

Enrollment Period

2.1 years

First QC Date

December 3, 2015

Results QC Date

May 8, 2019

Last Update Submit

July 12, 2019

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (2)

  • 6 Minute Walk Distance

    Change in distance walked between week 1 and week 13 were compared. The difference between the two time points is reported.

    Weeks 1, 13

  • Cardiopulmonary Exercise Test Work Rate

    Work rate (the amount of energy being expended to cycle) was assessed at weeks 1 and 13. The change in maximum work measured during CPET between weeks 1 and 13 is reported.

    Weeks 1 and 13

Secondary Outcomes (1)

  • Cystic Fibrosis Quality of Life-Revised Respiratory Domain Score

    Assessed at weeks 1 and 13

Study Arms (2)

Sildenafil

EXPERIMENTAL

Subjects will be randomized in a 3:1 (sildenafil:placebo) fashion. Subjects randomized to the treatment arm will receive sildenafil 20 mg p.o. t.i.d for 1 week followed by 40 mg p.o. t.i.d. for 11 weeks.

Drug: sildenafil

Placebo

PLACEBO COMPARATOR

Subjects randomized to the placebo arm will receive placebo p.o. t.i.d for 1 week followed by 2 placebo tablets p.o. t.i.d. for 11 weeks.

Drug: placebo

Interventions

sildenafilDRUG

active sildenafil

Also known as: Revatio, Viagra
Sildenafil
placeboDRUG

sugar pill that looks like sildenafil tablets

Placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Confirmed diagnosis of CF based on the following criteria: Positive sweat chloride ≥60mEq/liter (by pilocarpine iontophoresis) and/or Genotype with two identifiable mutations consistent with CF, and accompanied by one or more clinical features consistent with the CF phenotype
  • Male or female patients ≥ 18 years of age
  • FEV1 ≥ 20% predicted and ≤ 70% predicted (Hankinson)
  • Clinically stable without evidence of acute upper or lower respiratory tract infection or current pulmonary exacerbation within the 14 days prior to the screening visit
  • Ability to reproducibly perform spirometry (according to ATS criteria)
  • Ability to understand and sign a written informed consent or assent and comply with the requirements of the study
  • Willingness to maintain chronic CF medication schedule (e.g. alternating month inhaled antibiotics)

You may not qualify if:

  • History of hypersensitivity to sildenafil
  • Use of an investigational agent within the 4-week period prior to Visit 1 (Day 0)
  • Breastfeeding, pregnant, or verbal expression of unwillingness to practice an acceptable birth control method (abstinence, hormonal or barrier methods, partner sterilization or intrauterine device) during participation in the study for women of child-bearing potential.
  • History of significant hepatic disease (AST or ALT \> 5 times the upper limit of normal at screening, documented biliary cirrhosis, or portal hypertension),
  • History of significant cardiovascular disease (history of aortic stenosis, coronary artery disease, or life-threatening arrhythmia),
  • History of severe neurological disease (e.g. history of stroke),
  • History of severe hematologic disease (e.g. history of bleeding diathesis; current INR \> 2.0
  • History of severe ophthalmologic disease (e.g. history of retinal impairment or non-arteritic ischemic optic neuritis)
  • History of severe renal impairment (creatinine \>1.8 mg/dL.)
  • Inability to swallow pills
  • Previous organ transplantation
  • Use of concomitant nitrates, α-blocker, or Ca channel blocker (currently or within one month of Visit 1)
  • History of sputum or throat swab culture yielding Burkholderia cepacia or Mycobacterium massiliense within 2 years of screening
  • Weight less than 40 kg at Screening
  • History of migraine headaches.
  • +5 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

National Jewish Health

Denver, Colorado, 80206, United States

Location

Related Publications (9)

  • Orenstein DM, Higgins LW. Update on the role of exercise in cystic fibrosis. Curr Opin Pulm Med. 2005 Nov;11(6):519-23. doi: 10.1097/01.mcp.0000181476.92810.07.

    PMID: 16217178BACKGROUND

  • Pianosi P, Leblanc J, Almudevar A. Peak oxygen uptake and mortality in children with cystic fibrosis. Thorax. 2005 Jan;60(1):50-4. doi: 10.1136/thx.2003.008102.

    PMID: 15618583BACKGROUND

  • Almajed A, Lands LC. The evolution of exercise capacity and its limiting factors in cystic fibrosis. Paediatr Respir Rev. 2012 Dec;13(4):195-9. doi: 10.1016/j.prrv.2012.01.001. Epub 2012 Feb 10.

    PMID: 23069115BACKGROUND

  • Jiang K, Jiao S, Vitko M, Darrah R, Flask CA, Hodges CA, Yu X. The impact of Cystic Fibrosis Transmembrane Regulator Disruption on cardiac function and stress response. J Cyst Fibros. 2016 Jan;15(1):34-42. doi: 10.1016/j.jcf.2015.06.003. Epub 2015 Jun 25.

    PMID: 26119592BACKGROUND

  • Galie N, Ghofrani HA, Torbicki A, Barst RJ, Rubin LJ, Badesch D, Fleming T, Parpia T, Burgess G, Branzi A, Grimminger F, Kurzyna M, Simonneau G; Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group. Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med. 2005 Nov 17;353(20):2148-57. doi: 10.1056/NEJMoa050010.

    PMID: 16291984BACKGROUND

  • Mourani PM, Sontag MK, Ivy DD, Abman SH. Effects of long-term sildenafil treatment for pulmonary hypertension in infants with chronic lung disease. J Pediatr. 2009 Mar;154(3):379-84, 384.e1-2. doi: 10.1016/j.jpeds.2008.09.021. Epub 2008 Oct 31.

    PMID: 18950791BACKGROUND

  • Montgomery GS, Sagel SD, Taylor AL, Abman SH. Effects of sildenafil on pulmonary hypertension and exercise tolerance in severe cystic fibrosis-related lung disease. Pediatr Pulmonol. 2006 Apr;41(4):383-5. doi: 10.1002/ppul.20393.

    PMID: 16479610BACKGROUND

  • Lubamba B, Lecourt H, Lebacq J, Lebecque P, De Jonge H, Wallemacq P, Leal T. Preclinical evidence that sildenafil and vardenafil activate chloride transport in cystic fibrosis. Am J Respir Crit Care Med. 2008 Mar 1;177(5):506-15. doi: 10.1164/rccm.200703-344OC. Epub 2007 Nov 15.

    PMID: 18006891BACKGROUND

  • Taylor-Cousar JL, Wiley C, Felton LA, St Clair C, Jones M, Curran-Everett D, Poch K, Nichols DP, Solomon GM, Saavedra MT, Accurso FJ, Nick JA. Pharmacokinetics and tolerability of oral sildenafil in adults with cystic fibrosis lung disease. J Cyst Fibros. 2015 Mar;14(2):228-36. doi: 10.1016/j.jcf.2014.10.006. Epub 2014 Nov 13.

    PMID: 25466700BACKGROUND

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

Sildenafil Citrate

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

SulfonamidesAmidesOrganic ChemicalsSulfonesSulfur CompoundsPiperazinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsPurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-Ring

Results Point of Contact

Title
Jennifer Taylor-Cousar, MD, MSCS, ATSF
Organization
National Jewish Health
Taylor-CousarJ@NJHealth.org
3032702764

Study Officials

  • Jennifer L Taylor-Cousar, MD

    National Jewish Health

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Associate Professor

Study Record Dates

First Submitted

December 3, 2015

First Posted

December 10, 2015

Study Start

December 1, 2015

Primary Completion

January 18, 2018

Study Completion

January 29, 2018

Last Updated

July 24, 2019

Results First Posted

July 15, 2019

Record last verified: 2019-07

Locations

US(1)