Cystic FibrosisPhase 2NCT01772758
Cystic Fibrosis and Endothelial Function: At Rest and During Exercise
A Phase 2 study testing BH4 5mg, BH4 20mg and Antioxidant Cocktail in people with Cystic Fibrosis, run by Augusta University at 1 site in United States.
Trial summary
Perhaps one of the most disturbing aspects of Cystic Fibrosis (CF) is the associated premature death. Oxidative stress has been observed in patients with CF and exercise intolerance has been shown to predict mortality in patients with CF, regardless of how healthy their lungs are. Read more about this study
- Who is it for?
- Ages 7 years and olderHealthy volunteers can take part
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- BH4 5mg, BH4 20mg and Antioxidant Cocktail
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 64 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2011to 21 Jun 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 7 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Diagnosis of CF and healthy controls
- Men and women (> 18 yrs. old)
- Boys and girls (7 -17 yrs. old)
- FEV1 percent predicted > 30%
- Resting oxygen saturation (room air) >90%
- Patients with or without CFRD
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- Traditional CF-treatment medications
- Ability to perform reliable/reproducible PFTs
- Clinically stable for 2 weeks (no exacerbations or need for antibiotic treatment within 2 weeks of testing or major change in medical status)
Who cannot join
- Children 6 yrs. old and younger
- FEV1 percent predicted < 30%
- Resting oxygen saturation (room air) < 90%
- Clinical diagnosis of heart disease
- Pulmonary artery hypertension
- Febrile illness within two weeks of visit
Show all 11Show fewer
- Current smokers
- Currently pregnant or nursing
- Individuals on vaso-active medications (i.e. nitrates, beta blockers, ACE inhibitors, etc.)
- Inability to swallow pills
- Patients with B. Cepacia (only ~3% of our CF center patient population)
Trial locations and contacts
1 site in 1 country.
United States1 site
Georgia Prevention Institute/ Laboratory of Integrative and Exercise Physiology
Augusta, Georgia, 30912
About this study
Official title: Influence of Cystic Fibrosis on Vascular Endothelial Function at Rest and During Exercise
Perhaps one of the most disturbing aspects of Cystic Fibrosis (CF) is the associated premature death. Oxidative stress has been observed in patients with CF and exercise intolerance has been shown to predict mortality in patients with CF, regardless of how healthy their lungs are. A critical barrier to improving the quality of life and longevity in patients with CF is our lack of knowledge regarding the different reasons why patients with CF cannot exercise to the level of their peers. We have collected preliminary data to support our central hypothesis that oxidative stress contributes to the impairment in blood vessel function at rest and during exercise which ultimately oxygen transport and delivery resulting in exercise intolerance. Exercise is therapeutic medicine for patients with CF and this investigation represents a major breakthrough in the approach to begin understanding the physiological mechanisms which contribute to exercise intolerance in these patients.
Read the detailed description
The overall goals of this proposal are to provide mechanistic evidence that oxidative stress contributes to 1) endothelial dysfunction and 2) exercise intolerance in patients with CF. This study consists of two separate sub-studies, or protocols. Protocol 1: AOC tested the effect of an antioxidant cocktail (AOC) on endothelial function at rest and during exercise in CF patients. Protocol 2: BH4 tested the effect of tetrahydrobiopterin (BH4) on endothelial function at rest and during exercise in CF patients.
- Conditions
- Cystic Fibrosis
- Being tested
- BH4 5mg, BH4 20mg, Antioxidant Cocktail
- Keywords
- CF, cystic fibrosis, exercise
- Medical subject headings
- Cystic Fibrosis, Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BH4 5mgDrug
Also called Tetrahydrobiopterin, Kuvan
Kuvan® or sapropterin dihydrochloride is a synthetic preparation of the dihydrochloride salt of naturally occurring tetrahydrobiopterin (BH4). Subjects received an oral dose of 5 mg/kg of Kuvan® (Biomarin Pharmaceuticals Inc.)
BH4 20mgDrug
Also called Tetrahydrobiopterin, Kuvan
Kuvan® or sapropterin dihydrochloride is a synthetic preparation of the dihydrochloride salt of naturally occurring tetrahydrobiopterin (BH4). Subjects received an oral dose of 20 mg/kg of Kuvan® (Biomarin Pharmaceuticals Inc.)
Antioxidant CocktailDietary supplement
Vitamin C (1000 mg) , Vitamin E (600 IU) , and alpha-lipoic acid (600 mg). all BID
| Study group | Role | What they receive |
|---|---|---|
| Protocol 1: AOC | Experimental | measurements at baseline and 2 hours following the antioxidant cocktail that is comprised of over the counter vitamins (vitamin C 1000mg, vitamin E 600 IU, and alpha lipoic acid 600 mg) that will be given in two doses, 30 minutes apart. Receives: Dietary Supplement: Antioxidant Cocktail |
| Protocol 2: BH4 (5mg) | Experimental | measurements at baseline and 3 hours following the single dose of 5mg/kg Kuvan® or sapropterin dihydrochloride which is a synthetic preparation of the dihydrochloride salt of naturally occurring tetrahydrobiopterin (BH4).BH4 has been shown in past studies to increase NO bioavailability. Receives: Drug: BH4 5mg |
| Protocol 2: BH4 (20mg) | Experimental | measurements at baseline and 3 hours following the single dose of 20mg/kg Kuvan® or sapropterin dihydrochloride which is a synthetic preparation of the dihydrochloride salt of naturally occurring tetrahydrobiopterin (BH4).BH4 has been shown in past studies to increase NO bioavailability. Receives: Drug: BH4 20mg |
| Healthy Controls | No intervention | baseline measurements were done with no intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage Flow-Mediated Dilation (FMD)
Brachial artery FMD induced by reactive hyperemia assessed vascular endothelial function at baseline and several hours after treatment.
Measured: pre-treatment Baseline and 2-3 hours post-treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jan 2013 (estimated)
- Study startAug 2011
- Primary completion21 Jun 2016
- Study completion21 Jun 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- Augusta University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ryan Harris, Augusta University
- Investigators
- Ryan Harris, PhD, CES, Principal investigator, Augusta University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01772758
- Sponsor's protocol ID
- CFD Study
- Status last verified
- Jun 2019
- First submitted
- 16 Oct 2012
- Last updated
- 20 Jun 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Influence of Cystic Fibrosis on Vascular Endothelial Function at Rest and During Exercise
- ClinicalTrials.gov ID
- NCT01772758
- Acronym / sponsor ID
- CFD Study
- Conditions
- Cystic Fibrosis
- Keywords
- CF, cystic fibrosis, exercise
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 64 participants (actual)
- Lead sponsor
- Augusta UniversityUniversity, hospital or other
- Study start
- Aug 2011
- Primary completion
- 21 Jun 2016 (actual)
- Study completion
- 21 Jun 2016 (actual)
- First posted
- 21 Jan 2013 (estimated)
- Results
- Posted 10 Jan 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Perhaps one of the most disturbing aspects of Cystic Fibrosis (CF) is the associated premature death. Oxidative stress has been observed in patients with CF and exercise intolerance has been shown to predict mortality in patients with CF, regardless of how healthy their lungs are. A critical barrier to improving the quality of life and longevity in patients with CF is our lack of knowledge regarding the different reasons why patients with CF cannot exercise to the level of their peers. We have collected preliminary data to support our central hypothesis that oxidative stress contributes to the impairment in blood vessel function at rest and during exercise which ultimately oxygen transport and delivery resulting in exercise intolerance. Exercise is therapeutic medicine for patients with CF and this investigation represents a major breakthrough in the approach to begin understanding the physiological mechanisms which contribute to exercise intolerance in these patients.
Detailed description
The overall goals of this proposal are to provide mechanistic evidence that oxidative stress contributes to 1) endothelial dysfunction and 2) exercise intolerance in patients with CF. This study consists of two separate sub-studies, or protocols. Protocol 1: AOC tested the effect of an antioxidant cocktail (AOC) on endothelial function at rest and during exercise in CF patients. Protocol 2: BH4 tested the effect of tetrahydrobiopterin (BH4) on endothelial function at rest and during exercise in CF patients.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Protocol 1: AOC | Experimental | Dietary Supplement: Antioxidant Cocktailmeasurements at baseline and 2 hours following the antioxidant cocktail that is comprised of over the counter vitamins (vitamin C 1000mg, vitamin E 600 IU, and alpha lipoic acid 600 mg) that will be given in two doses, 30 minutes apart. |
| Protocol 2: BH4 (5mg) | Experimental | Drug: BH4 5mgmeasurements at baseline and 3 hours following the single dose of 5mg/kg Kuvan® or sapropterin dihydrochloride which is a synthetic preparation of the dihydrochloride salt of naturally occurring tetrahydrobiopterin (BH4).BH4 has been shown in past studies to increase NO bioavailability. |
| Protocol 2: BH4 (20mg) | Experimental | Drug: BH4 20mgmeasurements at baseline and 3 hours following the single dose of 20mg/kg Kuvan® or sapropterin dihydrochloride which is a synthetic preparation of the dihydrochloride salt of naturally occurring tetrahydrobiopterin (BH4).BH4 has been shown in past studies to increase NO bioavailability. |
| Healthy Controls | No intervention | –baseline measurements were done with no intervention |
Who may qualify
- Ages
- 7 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- Diagnosis of CF and healthy controls
- Men and women (> 18 yrs. old)
- Boys and girls (7 -17 yrs. old)
- FEV1 percent predicted > 30%
- Resting oxygen saturation (room air) >90%
Key exclusion criteria (11 listed)
- Children 6 yrs. old and younger
- FEV1 percent predicted < 30%
- Resting oxygen saturation (room air) < 90%
- Clinical diagnosis of heart disease
- Pulmonary artery hypertension
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BH4 5mgAlso: Tetrahydrobiopterin, KuvanKuvan® or sapropterin dihydrochloride is a synthetic preparation of the dihydrochloride salt of naturally occurring tetrahydrobiopterin (BH4). Subjects received an oral dose of 5 mg/kg of Kuvan® (Biomarin Pharmaceuticals Inc.) | Drug | Protocol 2: BH4 (5mg) |
| BH4 20mgAlso: Tetrahydrobiopterin, KuvanKuvan® or sapropterin dihydrochloride is a synthetic preparation of the dihydrochloride salt of naturally occurring tetrahydrobiopterin (BH4). Subjects received an oral dose of 20 mg/kg of Kuvan® (Biomarin Pharmaceuticals Inc.) | Drug | Protocol 2: BH4 (20mg) |
| Antioxidant CocktailVitamin C (1000 mg) , Vitamin E (600 IU) , and alpha-lipoic acid (600 mg). all BID | Dietary supplement | Protocol 1: AOC |
Primary outcome
Percentage Flow-Mediated Dilation (FMD)
Time frame: pre-treatment Baseline and 2-3 hours post-treatment
Brachial artery FMD induced by reactive hyperemia assessed vascular endothelial function at baseline and several hours after treatment.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jun 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Laboratory of Integrative and Exercise Physiology WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ryan Harris, PhD, CES principal investigator
Augusta University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing BH4 5mg, BH4 20mg and Antioxidant Cocktail in people with Cystic Fibrosis, run by Augusta University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Jan 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage Flow-Mediated Dilation (FMD) (time frame: pre-treatment Baseline and 2-3 hours post-treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jun 2019.