Clinical trial NCT02057458: Blood Flow and Vascular Function in Cystic Fibrosis
Official title: Role of Blood Flow and Vascular Function on Exercise Capacity in Cystic Fibrosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cystic Fibrosis
Keywords: arterial stiffness
flow-mediated dilation
endothelial function
pulse wave velocity
inflammation
oxidative stress
pulmonary function test
Cystic Fibrosis
Lung Disease
Nitric Oxide
Exercise Capacity
CF
Muscle Function
Sildenafil
Viagra
Revatio
Lead sponsor: Augusta University
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2014-02-07
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Cystic fibrosis (CF) has many health consequences. A reduction in the ability to perform exercise in patients with CF is related to greater death rates, steeper decline in lung function, and more frequent lung infections. However, the physiological mechanisms for this reduced exercise capacity are unknown. The investigators laboratory recently published the first evidence of systemic vascular dysfunction in patients with CF. Therefore, it is reasonable to suspect that the blood vessels are involved with exercise intolerance in CF. This study will look at how 1) blood flow and 2) artery function contribute to exercise capacity in CF.

Detailed description: The most disturbing aspect of Cystic Fibrosis (CF) is the associated premature death. Low exercise capacity predicts death in patients with CF and is also associated with a steeper decline in lung function and more lung infections. A critical barrier to improving exercise tolerance in patients with CF is the investigators lack of knowledge regarding the different physiological mechanisms which contribute to their lower exercise capacity. We have compelling data to indicate that the blood vessels may contribute to the low exercise capacity in CF. The impact of this proof of concept investigation will test Phosphodiesterase Type 5 inhibitors (PDE5) inhibitors as a potential therapy in CF and will explore blood flow and endothelial function as potential mechanisms which contribute to exercise intolerance in CF. Improvements in exercise capacity will not only contribute to a better quality of live for patients with CF, it will also increase longevity in these patients.

Eligibility criteria: Inclusion Criteria.

* Diagnosis of CF and healthy controls
* Men and women (greater than 18 yrs. old)
* Resting oxygen saturation (room air) greater than 90%
* Forced expiratory volume (FEV1) percent predicted greater than 30%
* Patients with or without CF related diabetes
* Traditional CF-treatment medications
* Ability to perform reliable/reproducible pulmonary function tests (PFT)
* Clinically stable for 2 weeks (no exacerbations or need for antibiotic treatment within 2 weeks of testing or major change in medical status)

Exclusion Criteria.

* Children less than 17 years old
* Body mass less than 20 kg
* A diagnosis of pulmonary arterial hypertension (PAH)
* FEV1 less than 30% of predicted
* Resting oxygen saturation (SpO2) less than 90%
* Self-reported to be a smoker
* Current use of any vaso-active medications
* History of migraine headaches
* Pregnant or nursing at the time of the investigation
* A clinical diagnosis of cardiovascular disease, hypertension, or CF related diabetes

Primary outcomes:
measure: Acute Study: Percentage Flow-Mediated Dilation (FMD)
timeFrame: pre-treatment Baseline and 1 hour post-treatment
measure: Baseline Diameter
timeFrame: pre-treatment Baseline and following 4 weeks sub-chronic treatment
measure: Peak Diameter
timeFrame: pre-treatment Baseline and following 4 weeks sub-chronic treatment
measure: Absolute Change in Diameter
timeFrame: pre-treatment Baseline and following 4 weeks sub-chronic treatment
measure: FEV1 (% Predicted)
timeFrame: pre-treatment Baseline, 1 hour post-treatment, and following 4 weeks sub-chronic treatment
measure: VO2 Peak (Absolute)
timeFrame: pre-treatment Baseline, 1 hour post-treatment, and following 4 weeks sub-chronic treatment
measure: VO2 Peak (Relative)
timeFrame: pre-treatment Baseline, 1 hour post-treatment, and following 4 weeks sub-chronic treatment
measure: VO2 Peak (Percent Predicted)
timeFrame: pre-treatment Baseline and 1 hour post-treatment, and 4 weeks sub-chronic treatment
measure: VE Peak
timeFrame: pre-treatment Baseline, 1 hour post-treatment, and following 4 weeks sub-chronic treatment
measure: RER Peak
timeFrame: pre-treatment Baseline, 1 hour post-treatment, and following 4 weeks sub-chronic treatment
Secondary outcomes:
Other outcomes:
Locations:
city: Augusta
country: United States
facility: Augusta University
state: Georgia
Study officials:
affiliation: Augusta University
name: Ryan Harris, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rodriguez-Miguelez P, Seigler N, Ishii H, Crandall R, McKie KT, Forseen C, Harris RA. Exercise Intolerance in Cystic Fibrosis: Importance of Skeletal Muscle. Med Sci Sports Exerc. 2021 Apr 1;53(4):684-693. doi: 10.1249/MSS.0000000000002521.