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Neurovascular Transduction During Exercise in Chronic Kidney Disease

ConditionRenal Insufficiency, Chronic
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-75
SponsorEmory University

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

severe CKD (eGFR<15 cc/minute)

ongoing drug or alcohol abuse

diabetic neuropathy

any serious systemic disease that might influence survival

Trial design

Design model

Factorial

Treatments tested in this trial

  • 6R-BH4

    Drug

    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

    Other intervention

    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

    Dietary supplement

    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

    Other intervention

    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

    Other intervention

    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

    Dietary supplement

    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

    Other intervention

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

Treatment groups

150 Participants
are divided into 6 treatment groups

6

Treatment groups

See each treatment group below.

Group A: Exercise training + 6R-BH4Experimental treatment 3 interventions
Group B: Exercise training + 6R-BH4 placeboActive comparator 3 interventions
Group C: Stretching + 6R-BH4Active comparator 3 interventions
Group D: Stretching + placeboPlacebo comparator 3 interventions
Group E: Exercise training + histidine and beta-alanineActive comparator 2 interventions
Group F: Exercise training + histidine and beta-alanine placeboActive comparator 2 interventions

Trial outcomes

Primary outcomes

1

Change in functional sympatholysis

Muscle oxygenation during exercise and sympathoexcitation will be measured.

Time frame
Baseline, Week 12
2

Change in vascular alpha 1 adrenergic responsiveness

Changes in vascular diameter in response to phenylephrine will be measured.

Time frame
Baseline, Week 12
3

Change in exaggerated pressor responses during exercise

Blood pressure and sympathetic responses during exercise will be measured.

Time frame
Baseline, Week 12

Secondary outcomes

1

Renal artery resistance during exercise

Renal artery blood flow will be measured.

Time frame
Baseline, Week 12
2

Change in endothelial function

Endothelial function using peripheral arterial tonometry will be measured.

Time frame
Baseline, Week 12
3

Change in vascular stiffness

Vascular stiffness using applanation tonometry.

Time frame
Baseline, Week 12

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Emory University

Lead sponsor

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Source ClinicalTrials.gov
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