Recruiting
Phase 2

Observational Study

Sponsor:

Emory University

Code:

NCT02947750

Conditions

Renal Insufficiency, Chronic

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

6R-BH4

6R-BH4 placebo

Folic acid

Exercise training

Stretching

Study Details

Brief summary:

The purpose of this study is to find out why patients with chronic kidney disease (CKD) have poor exercise capacity and to explore what causes an increase in blood pressure during exercise (i.e. increased adrenaline levels, or decreased ability of blood vessels to dilate). This study will also test whether or not regular exercise on a bicycle and/or treatment with 6R-BH4 (Kuvan) pills, or histidine and beta-alanine supplementation improves these measures during exercise. 6R-BH4 is currently FDA-approved for use in patients with certain forms of a disease called phenylketonuria, but it is not currently FDA approved for blood pressure or exercise capacity in people with CKD.

Conditions

Renal Insufficiency, Chronic

Study ID

NCT02947750

Start date

Oct, 2016

Status verified date

May, 2026

Completion date

Apr 30, 2027

Anticipated

Primary completion date

Apr 30, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

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 Design

Enrollment

150 participants

Anticipated

Allocation

Randomized

Intervention Model

Factorial

Primary purpose

Supportive Care

Interventions and Outcome Measures

Arms

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.

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.

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.

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.

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.

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.

Interventions

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.

6R-BH4 placebo

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.

Folic acid

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

Exercise training

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.

Stretching

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.

Histidine and beta-alanine supplementation

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.

Histidine and beta-alanine placebo

Participants randomized to this study arm will receive a placebo to match combined histidine (4g/day) and beta-alanine (3.2g/day) supplementation.

Primary outcome measure

  • Change in functional sympatholysis [ Time Frame: Baseline, Week 12 ]
  • Change in vascular alpha 1 adrenergic responsiveness [ Time Frame: Baseline, Week 12 ]
  • Change in exaggerated pressor responses during exercise [ Time Frame: Baseline, Week 12 ]

Central Contacts and Locations

Central contacts

Jeanie Park, MD

404-727-2525jeanie.park@emory.edu

Locations

Emory University Hospital Midtown

Recruiting

Atlanta, Georgia, United States, 30308

Contacts

Dana DaCosta

404-727-7762drdacos@emory.edu

Principal Investigator:

Jeanie Park, MD

Emory University Hospital

Recruiting

Atlanta, Georgia, United States, 30322

Contacts

Dana DaCosta

404-727-7762drdacos@emory.edu

Principal Investigator:

Jeanie Park, MD

Atlanta VA Health Care System

Recruiting

Decatur, Georgia, United States, 30033

Contacts

Dana DaCosta

404-727-7762drdacos@emory.edu

Melanie Kankam

404-321-6111mljeffe@emory.edu

Principal Investigator:

Jeanie Park, MD

More Information

Sponsor

Emory University

Last update posted

May 18, 2026

Last verified

May, 2026

Keywords

  • Hypertension
  • Kidney Disorder
  • Nephrology
  • Physiology

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Emory University on 2026-05-18.