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| ID | Type | Description | Link |
|---|---|---|---|
| R21DK100783 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Acute Study: Sildenafil first, then Placebo | Experimental | In randomized order, on two separate days, endothelial function and exercise capacity will be determined 1 hour following a single dose of sildenafil (50 mg) or placebo. |
|
| Acute Study: Placebo first, then Sildenafil | Experimental | In randomized order, on two separate days, endothelial function and exercise capacity will be determined 1 hour following a single dose of sildenafil (50 mg) or placebo. |
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| Sub-Chronic Study Sildenafil | Experimental | Following the acute study, patients will be instructed to take 20 mg of sildenafil, three times a day, for 4 weeks. Endothelial function will be determined within 48 hours following the last dose. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sildenafil (Acute-1 hour) | Drug | Vascular function will be assessed 1 hour following oral ingestion of sildenafil (50 mg) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Acute Study: Percentage Flow-Mediated Dilation (FMD) | FMD determined one hour after ingestion of 50 mg Sildenafil or placebo | pre-treatment Baseline and 1 hour post-treatment |
| Baseline Diameter | Brachial Artery Diameter during FMD (pre-occlusion or "baseline") | pre-treatment Baseline and following 4 weeks sub-chronic treatment |
| Peak Diameter | Peak Brachial Artery Diameter during FMD (post-occlusion) | pre-treatment Baseline and following 4 weeks sub-chronic treatment |
| Absolute Change in Diameter | Absolute change in brachial artery diameter taken from the FMD assessment | pre-treatment Baseline and following 4 weeks sub-chronic treatment |
| FEV1 (% Predicted) | Forced Expiratory Volume in the first second expressed as a percent predicted. | pre-treatment Baseline, 1 hour post-treatment, and following 4 weeks sub-chronic treatment |
| VO2 Peak (Absolute) | absolute (L/min) peak oxygen consumption during maximal exercise test | pre-treatment Baseline, 1 hour post-treatment, and following 4 weeks sub-chronic treatment |
| VO2 Peak (Relative) | relative (mL/kg/min) peak oxygen consumption during maximal exercise test | pre-treatment Baseline, 1 hour post-treatment, and following 4 weeks sub-chronic treatment |
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Inclusion Criteria.
Exclusion Criteria.
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| Name | Affiliation | Role |
|---|---|---|
| Ryan Harris, Ph.D. | Augusta University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Augusta University | Augusta | Georgia | 30912 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33105385 | Derived | 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. |
| Label | URL |
|---|---|
| Laboratory of Integrative Vascular and Exercise Physiology | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Acute Study: Sildenafil First, Then Placebo | In randomized order, on two separate days, endothelial function and exercise capacity will be determined 1 hour following a single dose of sildenafil (50 mg) or placebo. |
| FG001 | Acute Study: Placebo First, Then Sildenafil | In randomized order, on two separate days, endothelial function and exercise capacity will be determined 1 hour following a single dose of sildenafil (50 mg) or placebo. |
| FG002 | Sub-Chronic Only | participants who were unable to participate in the acute study due to distance from lab but participated in sub-chronic |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Recruited for Participation |
| |||||||||||||
| Met Inclusion Criteria |
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| Acute Study (1 Hour): First Intervention |
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| Acute Study (1 Hour): Second Int. |
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| Sub-Chronic Study (4 Weeks) |
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| ID | Title | Description |
|---|---|---|
| BG000 | Overall Study | Baseline characteristics reported for the overall study |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Acute Study: Percentage Flow-Mediated Dilation (FMD) | FMD determined one hour after ingestion of 50 mg Sildenafil or placebo | Posted | Mean | Standard Deviation | percent flow mediated dilation | pre-treatment Baseline and 1 hour post-treatment |
|
|
2 years, 4 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Overall Study | Overall Study | 0 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Ryan Harris, PhD | Augusta University | 7067215998 | ryharris@augusta.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 27, 2014 | Apr 3, 2020 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D003550 | Cystic Fibrosis |
| D007249 | Inflammation |
| D008171 | Lung Diseases |
| ID | Term |
|---|---|
| D010182 | Pancreatic Diseases |
| D004066 | Digestive System Diseases |
| D012140 | Respiratory Tract Diseases |
| D030342 | Genetic Diseases, Inborn |
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| ID | Term |
|---|---|
| D000068677 | Sildenafil Citrate |
| ID | Term |
|---|---|
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D013450 | Sulfones |
| D013457 |
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| Sildenafil (Subchronic-4 weeks) | Drug | Vascular function will be assessed 4 weeks following 20 mg three times per day (TID) of sildenafil for four weeks |
|
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| Placebo | Drug | Sugar pill designed to mimic the sildenafil treatment |
|
| VO2 Peak (Percent Predicted) | Maximal Oxygen consumption expressed as percent predicted taken from maximal exercise test. | pre-treatment Baseline and 1 hour post-treatment, and 4 weeks sub-chronic treatment |
| VE Peak | peak ventilation (L/min) during maximal exercise test | pre-treatment Baseline, 1 hour post-treatment, and following 4 weeks sub-chronic treatment |
| RER Peak | peak respiratory exchange ratio during maximal exercise test | pre-treatment Baseline, 1 hour post-treatment, and following 4 weeks sub-chronic treatment |
| NOT COMPLETED |
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| NOT COMPLETED |
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| NOT COMPLETED |
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| NOT COMPLETED |
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| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Height | Mean | Standard Deviation | cm |
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| Weight | Mean | Standard Deviation | kg |
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| Body mass index | Mean | Standard Deviation | kg/m^2 |
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| Body fat | Mean | Standard Deviation | % |
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| O2 saturation | Mean | Standard Deviation | % |
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| Systolic blood pressure | Mean | Standard Deviation | mmHg |
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| Diastolic blood pressure | Mean | Standard Deviation | mmHg |
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| Participants |
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| Primary | Baseline Diameter | Brachial Artery Diameter during FMD (pre-occlusion or "baseline") | Posted | Mean | Standard Deviation | mm | pre-treatment Baseline and following 4 weeks sub-chronic treatment |
|
|
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| Primary | Peak Diameter | Peak Brachial Artery Diameter during FMD (post-occlusion) | Posted | Mean | Standard Deviation | mm | pre-treatment Baseline and following 4 weeks sub-chronic treatment |
|
|
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| Primary | Absolute Change in Diameter | Absolute change in brachial artery diameter taken from the FMD assessment | Posted | Mean | Standard Deviation | mm | pre-treatment Baseline and following 4 weeks sub-chronic treatment |
|
|
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| Primary | FEV1 (% Predicted) | Forced Expiratory Volume in the first second expressed as a percent predicted. | Posted | Mean | Standard Deviation | percent predicted | pre-treatment Baseline, 1 hour post-treatment, and following 4 weeks sub-chronic treatment |
|
|
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| Primary | VO2 Peak (Absolute) | absolute (L/min) peak oxygen consumption during maximal exercise test | Posted | Mean | Standard Deviation | L/min | pre-treatment Baseline, 1 hour post-treatment, and following 4 weeks sub-chronic treatment |
|
|
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| Primary | VO2 Peak (Relative) | relative (mL/kg/min) peak oxygen consumption during maximal exercise test | Posted | Mean | Standard Deviation | mL/kg/min | pre-treatment Baseline, 1 hour post-treatment, and following 4 weeks sub-chronic treatment |
|
|
|
| Primary | VO2 Peak (Percent Predicted) | Maximal Oxygen consumption expressed as percent predicted taken from maximal exercise test. | Posted | Mean | Standard Deviation | percent predicted | pre-treatment Baseline and 1 hour post-treatment, and 4 weeks sub-chronic treatment |
|
|
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| Primary | VE Peak | peak ventilation (L/min) during maximal exercise test | Posted | Mean | Standard Deviation | L/min | pre-treatment Baseline, 1 hour post-treatment, and following 4 weeks sub-chronic treatment |
|
|
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| Primary | RER Peak | peak respiratory exchange ratio during maximal exercise test | Posted | Mean | Standard Deviation | ratio | pre-treatment Baseline, 1 hour post-treatment, and following 4 weeks sub-chronic treatment |
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| 18 |
| 0 |
| 18 |
| 0 |
| 18 |
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| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D007232 | Infant, Newborn, Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| Sulfur Compounds |
| D010879 | Piperazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |