What side effects are associated with this type of intervention?

Common treatments for Chronic Kidney Disease (CKD) include medications to manage blood pressure, blood glucose, and cholesterol levels, as well as drugs to reduce proteinuria and control anemia. Treatments similar to 6R-BH4 (Kuvan), which aid in blood vessel dilation, may include antihypertensive agents like ACE inhibitors and ARBs. Known side effects of these treatments can include hyperkalemia, hypotension, and renal function deterioration. Additionally, erythropoiesis-stimulating agents used for anemia management can cause hypertension and increased risk of thromboembolic events. Overall, while these treatments are essential for managing CKD, they require careful monitoring to mitigate potential adverse effects.

What prior FDA approvals exist?

The FDA has approved several treatments for Chronic Kidney Disease (CKD) that focus on improving renal function and aiding blood vessel dilation. Notably, renin-angiotensin system (RAS) blockers such as enalapril and lisinopril are commonly used to manage hypertension and reduce proteinuria in CKD patients. These drugs help in dilating blood vessels and reducing blood pressure, thereby protecting kidney function. Additionally, semaglutide, a GLP-1 receptor agonist, has shown nephroprotective effects in diabetic kidney disease. While 6R-BH4 (Kuvan) is not yet FDA-approved for CKD, it is being studied for its potential benefits in improving blood vessel dilation and exercise capacity in CKD patients.

What other types of research exist?

One promising alternative to 6R-BH4 (Kuvan) for CKD patients is tempol, a superoxide dismutase (SOD) mimetic. Chronic oral treatment with tempol has been shown to prevent increases in renal vascular resistance and nitrotyrosine levels, which are beneficial for renal hemodynamics. Additionally, therapies targeting nitric oxide (NO) signaling, such as those involving GTP cyclohydrolase I (GTPCH I) activation, may also be considered as they have shown efficacy in restoring NO/cGMP signaling in hypertensive models.

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Exercise & Supplements for Chronic Kidney Disease (NeurovEx Trial)

Phase 2

Recruiting

Led By Joe Nocera, PhD

Research Sponsored by Emory University

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Stable renal function, with no greater than a 30% reduction in eGFR over the prior 3 months

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

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline, week 12

Summary

This trial aims to see if regular cycling exercise, a medication called Kuvan, and common sports supplements can help people with chronic kidney disease improve their exercise ability and manage blood pressure during exercise.

Who is the study for?

This trial is for adults with moderate to severe chronic kidney disease (stages III or IV), which means their kidneys don't filter blood well. They should have stable kidney function without major changes in the last 3 months and not be regular exercisers, working out less than 40 minutes per week.

What is being tested?

The study looks at why patients with CKD struggle with exercise and high blood pressure during it. It tests if cycling, a drug called Kuvan (6R-BH4), or supplements like histidine and beta-alanine can help improve these issues. Some participants will receive placebos instead of actual drugs.

What are the potential side effects?

Possible side effects may include reactions to supplements or medication such as digestive discomfort, skin reactions, headaches, or dizziness. Exercise might cause muscle soreness or fatigue.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

My kidney function has been stable, with less than a 30% drop in efficiency.

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My kidney function is moderately to severely reduced.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline, week 12

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline, week 12

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline, week 12 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change in exaggerated pressor responses during exercise

Change in functional sympatholysis

Change in vascular alpha 1 adrenergic responsiveness

Secondary study objectives

Change in endothelial function

Change in vascular stiffness

Renal artery resistance during exercise

Trial Design

6Treatment groups

Experimental Treatment

Active Control

Placebo Group

Group I: Exercise training + 6R-BH4Experimental Treatment3 Interventions

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.

Group II: Exercise training + histidine and beta-alanineActive Control2 Interventions

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.

Group III: Exercise training + histidine and beta-alanine placeboActive Control2 Interventions

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.

Group IV: Exercise training + 6R-BH4 placeboActive Control3 Interventions

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.

Group V: Stretching + 6R-BH4Active Control3 Interventions

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.

Group VI: Stretching + placeboPlacebo Group3 Interventions

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Folic acid

2008

Completed Phase 4

~8330

0 / 2Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Chronic Kidney Disease (CKD) often target oxidative stress, endothelial dysfunction, and inflammation. For instance, 6R-BH4 (Kuvan) enhances nitric oxide production, aiding in blood vessel dilation and improving endothelial function. Other treatments, such as antioxidants like N-acetylcysteine and Nrf2 activators like RTA dh404, reduce oxidative stress and inflammation. These mechanisms are vital for CKD patients as they address the root causes of disease progression, potentially improving cardiovascular health and slowing kidney damage.

Blockage of the Na-K-ATPase signaling-mediated oxidant amplification loop elongates red blood cell half-life and ameliorates uremic anemia induced by 5/6th PNx in C57BL/6 mice.Antioxidant and Anti-Inflammatory Strategies Based on the Potentiation of Glutathione Peroxidase Activity Prevent Endothelial Dysfunction in Chronic Kidney Disease.The Effect of Dietary Supplementation With Curcumin on Redox Status and Nrf2 Activation in Patients With Nondiabetic or Diabetic Proteinuric Chronic Kidney Disease: A Pilot Study.