- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02947750
Neurovascular Transduction During Exercise in Chronic Kidney Disease (NeurovEx)
Neurovascular Regulation During Exercise in Humans With Chronic Kidney Disease
Study Overview
Status
Conditions
Detailed Description
The major problem addressed in this study is to understand mechanisms underlying poor exercise capacity in patients with chronic kidney disease (CKD). Prior research has found that CKD patients have an exaggerated increase in blood pressure during certain forms of exercise that could contribute to exercise dysfunction as well as cardiovascular disease. This study will test the mechanisms underlying this exaggerated blood pressure response, as well as the potential benefits of simple measures such as exercise training on a stationary bicycle, and treatment with 6R-BH4, a drug that is currently FDA-approved for the treatment of phenylketonuria, but has been shown to have beneficial effects on vascular health in patients with kidney disease. This study will also examine the effects of exercise with histidine and beta-alanine supplementation. Histidine and beta-alanine are two over-the-counter supplements commonly used to enhance sports performance in athletes.
Prior to the intervention portion of this study, the researchers will measure how much the vein constricts in response to adrenaline in CKD patients versus controls. The study will also measure muscle pH, and muscle oxygenation during exercise in CKD patients and controls.
The intervention portion of the study will test whether aerobic exercise training with and without 6R-BH4, or with and without histidine and beta-alanine supplementation might help muscle pH and adrenaline levels, vascular reactivity, muscle oxygenation, and the exaggerated blood pressure response during exercise in CKD patients. Participants will be randomized using a 2x2 factorial design to exercise training (ET) with 6R-BH4, ET with placebo, stretching (control condition to exercise) with 6R-BH4, and stretching with placebo. Participants will undergo exercise training on a stationary bicycle, or stretching exercises, 3 times per week for 6-14 weeks (depending on availability of the participant).
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Jeanie Park, MD
- Phone Number: 404-727-2525
- Email: jeanie.park@emory.edu
Study Locations
-
-
Georgia
-
Atlanta, Georgia, United States, 30308
- Recruiting
- Emory University Hospital Midtown
-
Principal Investigator:
- Jeanie Park, MD
-
Contact:
- Dana DaCosta
- Phone Number: 404-727-7762
- Email: drdacos@emory.edu
-
Atlanta, Georgia, United States, 30322
- Recruiting
- Emory University Hospital
-
Principal Investigator:
- Jeanie Park, MD
-
Contact:
- Dana DaCosta
- Phone Number: 404-727-7762
- Email: drdacos@emory.edu
-
Decatur, Georgia, United States, 30033
- Recruiting
- Atlanta VA Health Care System
-
Principal Investigator:
- Jeanie Park, MD
-
Contact:
- Melanie Kankam
- Phone Number: 7040 404-321-6111
- Email: mljeffe@emory.edu
-
Contact:
- Dana DaCosta
- Phone Number: 404-727-7762
- Email: drdacos@emory.edu
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria for Chronic Kidney Disease Patients:
- Stage III or IV Chronic Kidney Disease, defined as reduction in estimated glomerular filtration rate (eGFR) to 15-59 cc/minute as calculated by the modified Modification of Diet in Renal Disease (MDRD) Study equation or the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation
- Stable renal function, with no greater than a 30% reduction in eGFR over the prior 3 months
- Does not exercise regularly (defined as exercising less than 20 minutes twice per week)
- Willing and able to cooperate with the study protocol
Inclusion Criteria for Control Study Participants:
- Does not exercise regularly (defined as exercising less than 20 minutes twice per week)
- Willing and able to cooperate with the study protocol
Exclusion Criteria:
- severe CKD (eGFR<15 cc/minute)
- ongoing drug or alcohol abuse
- diabetic neuropathy
- any serious systemic disease that might influence survival
- severe anemia with hgb level <9 g/dL
- clinical evidence of congestive heart failure or ejection fraction below 35%
- symptomatic heart disease determined by prior electrocardiogram, stress test, and/or history
- treatment with central alpha agonists (clonidine)
- uncontrolled hypertension with BP greater than 170/100 mm Hg
- low blood pressure with BP less than 100/50
- pregnancy or plans to become pregnant
- current treatment with monoamine oxidase (MAO) inhibitors
- inability to exercise on a stationary bicycle
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Supportive Care
- Allocation: Randomized
- Interventional Model: Factorial Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Exercise training + 6R-BH4
Participants randomized to this arm will exercise on a stationary bicycle for 20-45 minutes, 3 times per week, for 6-12 weeks.
This arm will also take the study drug 6R-BH4.
|
Participants will receive 200 mg of 6R-BH4 twice daily for 12 weeks.
Study pills are dissolved in water or apple juice, and taken with food.
Other Names:
Participants will take 1 mg of folic acid daily for 12 weeks.
Folic acid is given because it enhances the binding affinity of BH4 to nitric oxide synthase (NOS), and also enhances the regeneration of BH4 from inactive BH2
Participants will exercise 3 times a week on a stationary ergometer.
Exercise intensity will begin at low levels (50% of maximal heart rate reserve) calculated utilizing the Karvonen method.
Briefly, target exercise heart rate (HR) is calculated by subtracting the persons age from 220.
Resting heart rate is then subtracted from this number.
The answer is then multiplied by the target percent (50% for example) and the product is added back to resting heart rate to provide the target exercise session heart rate.
Intensity will be increased by 5% every week (as tolerated by the participant) to a maximum of 80% of maximal heart rate.
Exercise time will progress from an initial 20 minutes per session to a maximum of 45 minutes by increasing 5 minutes each week.
|
Active Comparator: Exercise training + 6R-BH4 placebo
Participants randomized to this arm will exercise on a stationary bicycle for 20-45 minutes, 3 times per week, for 6-12 weeks.
This arm will also take a placebo to match the study drug 6R-BH4.
|
Participants will take 1 mg of folic acid daily for 12 weeks.
Folic acid is given because it enhances the binding affinity of BH4 to nitric oxide synthase (NOS), and also enhances the regeneration of BH4 from inactive BH2
Participants will exercise 3 times a week on a stationary ergometer.
Exercise intensity will begin at low levels (50% of maximal heart rate reserve) calculated utilizing the Karvonen method.
Briefly, target exercise heart rate (HR) is calculated by subtracting the persons age from 220.
Resting heart rate is then subtracted from this number.
The answer is then multiplied by the target percent (50% for example) and the product is added back to resting heart rate to provide the target exercise session heart rate.
Intensity will be increased by 5% every week (as tolerated by the participant) to a maximum of 80% of maximal heart rate.
Exercise time will progress from an initial 20 minutes per session to a maximum of 45 minutes by increasing 5 minutes each week.
Participants will receive a placebo that is identical to 200 mg of 6R-BH4.
The placebo will be taken twice daily for 12 weeks.
Study pills are dissolved in water or apple juice, and taken with food.
|
Active Comparator: Stretching + 6R-BH4
Participants randomized to this arm will do muscle stretching and toning for 20-45 minutes, 3 times per week, for 6-12 weeks.
This arm will also take the study drug 6R-BH4.
|
Participants will receive 200 mg of 6R-BH4 twice daily for 12 weeks.
Study pills are dissolved in water or apple juice, and taken with food.
Other Names:
Participants will take 1 mg of folic acid daily for 12 weeks.
Folic acid is given because it enhances the binding affinity of BH4 to nitric oxide synthase (NOS), and also enhances the regeneration of BH4 from inactive BH2
Participants randomized to 'No Exercise Training' group will instead of aerobic exercise, undergo progressive whole body stretching and toning exercises designed for individuals 65 and older.
This type of low intensity activity is designed not to increase heart rate and will serve as the Control group to the Exercise Training group.
The Control group will come in for stretching sessions 3 times per week for 20-45 minutes.
Other Names:
|
Placebo Comparator: Stretching + placebo
Participants randomized to this arm will do muscle stretching and toning for 20-45 minutes, 3 times per week, for 6-12 weeks.
This arm will also take a placebo instead of the active study drug.
|
Participants will take 1 mg of folic acid daily for 12 weeks.
Folic acid is given because it enhances the binding affinity of BH4 to nitric oxide synthase (NOS), and also enhances the regeneration of BH4 from inactive BH2
Participants will receive a placebo that is identical to 200 mg of 6R-BH4.
The placebo will be taken twice daily for 12 weeks.
Study pills are dissolved in water or apple juice, and taken with food.
Participants randomized to 'No Exercise Training' group will instead of aerobic exercise, undergo progressive whole body stretching and toning exercises designed for individuals 65 and older.
This type of low intensity activity is designed not to increase heart rate and will serve as the Control group to the Exercise Training group.
The Control group will come in for stretching sessions 3 times per week for 20-45 minutes.
Other Names:
|
Active Comparator: Exercise training + histidine and beta-alanine
Participants randomized to this arm will exercise on a stationary bicycle for 20-45 minutes, 3 times per week, for 6-12 weeks.
This arm will also take histidine and beta-alanine supplementation.
|
Participants will exercise 3 times a week on a stationary ergometer.
Exercise intensity will begin at low levels (50% of maximal heart rate reserve) calculated utilizing the Karvonen method.
Briefly, target exercise heart rate (HR) is calculated by subtracting the persons age from 220.
Resting heart rate is then subtracted from this number.
The answer is then multiplied by the target percent (50% for example) and the product is added back to resting heart rate to provide the target exercise session heart rate.
Intensity will be increased by 5% every week (as tolerated by the participant) to a maximum of 80% of maximal heart rate.
Exercise time will progress from an initial 20 minutes per session to a maximum of 45 minutes by increasing 5 minutes each week.
Histidine and beta-alanine are two over-the-counter supplements commonly used to enhance sports performance in athletes.
Participants randomized to this study arm will receive combined histidine (4g/day) and beta-alanine (3.2g/day) supplementation.
|
Active Comparator: Exercise training + histidine and beta-alanine placebo
Participants randomized to this arm will exercise on a stationary bicycle for 20-45 minutes, 3 times per week, for 6-12 weeks.
This arm will also take a placebo to match the histidine and beta-alanine supplementation.
|
Participants will exercise 3 times a week on a stationary ergometer.
Exercise intensity will begin at low levels (50% of maximal heart rate reserve) calculated utilizing the Karvonen method.
Briefly, target exercise heart rate (HR) is calculated by subtracting the persons age from 220.
Resting heart rate is then subtracted from this number.
The answer is then multiplied by the target percent (50% for example) and the product is added back to resting heart rate to provide the target exercise session heart rate.
Intensity will be increased by 5% every week (as tolerated by the participant) to a maximum of 80% of maximal heart rate.
Exercise time will progress from an initial 20 minutes per session to a maximum of 45 minutes by increasing 5 minutes each week.
Participants randomized to this study arm will receive a placebo to match combined histidine (4g/day) and beta-alanine (3.2g/day) supplementation.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in functional sympatholysis
Time Frame: Baseline, Week 12
|
Muscle oxygenation during exercise and sympathoexcitation will be measured.
|
Baseline, Week 12
|
Change in vascular alpha 1 adrenergic responsiveness
Time Frame: Baseline, Week 12
|
Changes in vascular diameter in response to phenylephrine will be measured.
|
Baseline, Week 12
|
Change in exaggerated pressor responses during exercise
Time Frame: Baseline, Week 12
|
Blood pressure and sympathetic responses during exercise will be measured.
|
Baseline, Week 12
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Renal artery resistance during exercise
Time Frame: Baseline, Week 12
|
Renal artery blood flow will be measured.
|
Baseline, Week 12
|
Change in endothelial function
Time Frame: Baseline, Week 12
|
Endothelial function using peripheral arterial tonometry will be measured.
|
Baseline, Week 12
|
Change in vascular stiffness
Time Frame: Baseline, Week 12
|
Vascular stiffness using applanation tonometry.
|
Baseline, Week 12
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Joe Nocera, PhD, Emory University
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Urologic Diseases
- Disease Attributes
- Chronic Disease
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Male Urogenital Diseases
- Kidney Diseases
- Renal Insufficiency, Chronic
- Renal Insufficiency
- Physiological Effects of Drugs
- Micronutrients
- Vitamins
- Vitamin B Complex
- Hematinics
- Folic Acid
Other Study ID Numbers
- IRB00091660
- R01HL135183 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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