Kidney Failure, ChronicPhase 2EIRFNCT01356966
Exercise Intolerance in Renal Failure
A Phase 2 study testing Tetrahydrobiopterin and Folate in people with Kidney Failure, Chronic, run by Emory University at 2 sites in United States.
Trial summary
Patients with chronic kidney disease have profound exercise intolerance which contributes to an increased risk of cardiovascular disease. The investigators have found that chronic kidney disease patients have an exaggerated increase in blood pressure during certain forms of exercise that could certainly contribute to… Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Kidney Failure, Chronic
- What is being tested?
- Tetrahydrobiopterin and Folate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 74 participants
- Where
- 2 sitesUnited States
- Study dates
- May 2011to May 2014
- 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 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- chronic kidney disease (CKD) stages I, II, and III and do not regularly exercise
- 1. CKD Stages I, II, and III will be defined as reduction in estimated glomerular filtration rate (eGFR) to 30-59 cc/minute as calculated by the Modification of Diet in Renal Disease (MDRD) equation, or an eGFR>60 cc/minute with proteinuria greater than 500 mg/g of Creatinine or 500 mg per 24 hours.
- willing and able to cooperate with the protocol
- CKD patients must have stable renal function (no greater than a 20% reduction in eGFR over the prior 3 months)
- controls will be matched for age, gender, race, and hypertensive status.
Who cannot join
- severe CKD (eGFR<30 cc/minute)
- drug or alcohol abuse
- diabetes
- any serious systemic disease that might influence survival
- severe anemia with hgb level <10 g/dL
- clinical evidence of congestive heart failure or ejection fraction below 35%
Show all 21Show fewer
- any history of past myocardial infarction or cerebrovascular accident
- symptomatic heart disease determined by electrocardiogram, stress test, and/or history
- treatment with central alpha agonists
- uncontrolled hypertension with BP greater than 160/90 mm Hg
- low blood pressure with BP less than 110/60
- history of nephrolithiasis
- pregnancy or plans to become pregnant
- treatment with vitamin C within the past 3 months
- hepatic enzyme concentrations greater than 2 times the upper limit of normal
- HIV infection
- surgery within the past 3 months
- previous treatment with BH4
- known hypersensitivity to BH4
- any condition that places the participant at high risk of poor adherence or poor follow-up
- patients must be willing to use an acceptable method of contraception if of childbearing age
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Emory University Hospital
Atlanta, Georgia, 30322
Atlanta VA Medical Center
Decatur, Georgia, 30033
About this study
Official title: The Role of Neurovascular Dysfunction and Oxidative Stress in the Exercise Intolerance of Renal Failure
Patients with chronic kidney disease have profound exercise intolerance which contributes to an increased risk of cardiovascular disease. The investigators have found that chronic kidney disease patients have an exaggerated increase in blood pressure during certain forms of exercise that could certainly contribute to exercise dysfunction as well as cardiovascular risk. The investigators will test the mechanisms underlying this exaggerated blood pressure response, as well as the potential benefits of short-term tetrahydrobiopterin (BH4) with folic acid on both exercise dysfunction and cardiovascular risk factors in chronic kidney disease. The investigators will test whether short-term treatment with tetrahydrobiopterin (BH4), a cofactor for nitric oxide, together with folic acid improves inflammation, vascular health, and adrenaline levels, both at rest and during exercise in chronic kidney disease.
- Conditions
- Kidney Failure, Chronic
- Being tested
- Tetrahydrobiopterin, Placebo, Folate
- Medical subject headings
- Kidney Failure, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TetrahydrobiopterinDrug
Also called Kuvan
Tetrahydrobiopterin (BH4) 200 mg PO BID for 12 weeks
PlaceboDrug
2 placebo pills PO BID for12 weeks
FolateDietary supplement
Also called Folic Acid
Folate 1 mg daily for 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| Tetrahydrobiopterin + Folate | Experimental | Male subjects with hypertension and chronic kidney disease stage 2 or 3 will receive Tetrahydrobiopterin (6R-BH4) 200 mg twice daily and folic acid 1 mg daily Receives: Drug: Tetrahydrobiopterin; Dietary Supplement: Folate |
| Placebo + Folate | Placebo comparator | Male subjects with hypertension and chronic kidney disease stage 2 or 3 will receive 2 placebo pills twice daily and folic acid 1 mg daily Receives: Drug: Placebo; Dietary Supplement: Folate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Resting Muscle Sympathetic Nerve Activity (MSNA)
Measured: Baseline, 12 weeks
Secondary outcomes (2)
Change in Mean Central Augmentation Index (AIx)
The augmentation index (AIx) is a measure of systemic arterial stiffness, and is defined as the ratio of augmentation (Δ P) to central pulse pressure and expressed as percent. AIx = (ΔP/PP) x 100, where P = pressure and PP = Pulse Pressure. The mean AIx for each group was estimated as an average and expressed as a change from baseline to 12 weeks.
Measured: Baseline, 12 weeks
Change in Heart-rate-corrected Augmentation Index (AIx)
The augmentation index (AIx) is a measure of systemic arterial stiffness, and is defined as the ratio of augmented aortic pressure (Δ P) to central pulse pressure expressed as a percent. AIx = (ΔP/PP) x 100, where P = pressure and PP = Pulse Pressure. Because heart rate (HR) affects AIx, AIx was corrected to a HR of 75 beats per minute (bpm) as follows: HR-corrected AIx = -0.39 x (75 - HR) + AIx. The mean AIx for each group was estimated as an average and expressed as a change from baseline to 12 weeks.
Measured: Baseline, 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 May 2011 (estimated)
- Study startMay 2011
- Primary completionMay 2014
- Study completionMay 2014
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Kidney Failure, ChronicStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 74 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Jeanie Park, Emory University
- Investigators
- Jeanie Park, MD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01356966
- Sponsor's protocol ID
- IRB00019181
- Other IDs
- K23HL098744
- Acronym
- EIRF
- Status last verified
- May 2015
- First submitted
- 18 May 2011
- Last updated
- 1 Jun 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Lin AM, Liao P, Millson EC, Quyyumi AA, Park J. Tetrahydrobiopterin ameliorates the exaggerated exercise pressor response in patients with chronic kidney disease: a randomized controlled trial. Am J Physiol Renal Physiol. 2016 May 1;310(10):F1016-25. doi: 10.1152/ajprenal.00527.2015. Epub 2016 Mar 9.
PubMed 26962106
Study at a glance
From the registry record, last updated by the sponsor on 1 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Neurovascular Dysfunction and Oxidative Stress in the Exercise Intolerance of Renal Failure
- ClinicalTrials.gov ID
- NCT01356966
- Acronym / sponsor ID
- EIRF / IRB00019181
- Conditions
- Kidney Failure, Chronic
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 74 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- May 2011
- Primary completion
- May 2014 (actual)
- Study completion
- May 2014 (actual)
- First posted
- 20 May 2011 (estimated)
- Results
- Posted 1 Jun 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Patients with chronic kidney disease have profound exercise intolerance which contributes to an increased risk of cardiovascular disease. The investigators have found that chronic kidney disease patients have an exaggerated increase in blood pressure during certain forms of exercise that could certainly contribute to exercise dysfunction as well as cardiovascular risk. The investigators will test the mechanisms underlying this exaggerated blood pressure response, as well as the potential benefits of short-term tetrahydrobiopterin (BH4) with folic acid on both exercise dysfunction and cardiovascular risk factors in chronic kidney disease. The investigators will test whether short-term treatment with tetrahydrobiopterin (BH4), a cofactor for nitric oxide, together with folic acid improves inflammation, vascular health, and adrenaline levels, both at rest and during exercise in chronic kidney disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tetrahydrobiopterin + Folate | Experimental | Drug: Tetrahydrobiopterin, Dietary Supplement: FolateMale subjects with hypertension and chronic kidney disease stage 2 or 3 will receive Tetrahydrobiopterin (6R-BH4) 200 mg twice daily and folic acid 1 mg daily |
| Placebo + Folate | Placebo comparator | Drug: Placebo, Dietary Supplement: FolateMale subjects with hypertension and chronic kidney disease stage 2 or 3 will receive 2 placebo pills twice daily and folic acid 1 mg daily |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- chronic kidney disease (CKD) stages I, II, and III and do not regularly exercise
- 1. CKD Stages I, II, and III will be defined as reduction in estimated glomerular filtration rate (eGFR) to 30-59 cc/minute as calculated by the Modification of Diet in Renal Disease (MDRD) equation, or an eGFR>60 cc/minute with proteinuria greater than 500 mg/g of Creatinine or 500 mg per 24 hours.
- willing and able to cooperate with the protocol
- CKD patients must have stable renal function (no greater than a 20% reduction in eGFR over the prior 3 months)
- controls will be matched for age, gender, race, and hypertensive status.
Key exclusion criteria (21 listed)
- severe CKD (eGFR<30 cc/minute)
- drug or alcohol abuse
- diabetes
- any serious systemic disease that might influence survival
- severe anemia with hgb level <10 g/dL
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 |
|---|---|---|
| TetrahydrobiopterinAlso: KuvanTetrahydrobiopterin (BH4) 200 mg PO BID for 12 weeks | Drug | Tetrahydrobiopterin + Folate |
| Placebo2 placebo pills PO BID for12 weeks | Drug | Placebo + Folate |
| FolateAlso: Folic AcidFolate 1 mg daily for 12 weeks | Dietary supplement | Placebo + Folate, Tetrahydrobiopterin + Folate |
Primary outcome
Change in Resting Muscle Sympathetic Nerve Activity (MSNA)
Time frame: Baseline, 12 weeks
2 secondary outcomes
Change in Mean Central Augmentation Index (AIx)
Time frame: Baseline, 12 weeks
Change in Heart-rate-corrected Augmentation Index (AIx)
Time frame: Baseline, 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26962106Lin AM, Liao P, Millson EC, Quyyumi AA, Park J. Tetrahydrobiopterin ameliorates the exaggerated exercise pressor response in patients with chronic kidney disease: a randomized controlled trial. Am J Physiol Renal Physiol. 2016 May 1;310(10):F1016-25. doi: 10.1152/ajprenal.00527.2015. Epub 2016 Mar 9.
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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.
Jeanie Park, MD principal investigator
Emory University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tetrahydrobiopterin and Folate in people with Kidney Failure, Chronic, run by Emory University at 2 sites 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 5 inclusion and 21 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 1 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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. Some participants in this study may receive a placebo. 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 1 Jun 2015). 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?
Change in Resting Muscle Sympathetic Nerve Activity (MSNA) (time frame: Baseline, 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01356966, which also lists 1 linked publication.
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 1 Jun 2015.