Mechanisms of Muscle Blood Flow Dysregulation and Exercise Intolerance in Chronic Kidney Disease

Chronic Kidney Disease Clinical Trial

Official title:

Mechanisms of Muscle Blood Flow Dysregulation and Exercise Intolerance in Chronic Kidney Disease

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02664519
• Other study ID #: STU 092015-005
• Status: Terminated
• Phase: N/A
• Start date: January 2016
• Est. completion date: March 18, 2021

Study information

• Verified date: March 2021
• Source: University of Texas Southwestern Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Patients with chronic kidney disease (CKD) experience fatigue and exercise intolerance. Increased oxidative stress in CKD may be a contributing factor. The role of impaired muscle blood flow regulation has not been fully explored. The investigators hypothesize that functional sympatholysis is exaggerated in CKD and this is associated with increased oxidative stress. The investigators also hypothesize that exercise training will improve functional sympatholysis and oxidative stress

Description:

Progressive muscle weakness and premature fatigue are characterize the condition of chronic kidney disease (CKD) which can be very debilitating. Mechanisms underlying exercise intolerance in CKD is not completely understood. Previous studies have demonstrated impaired skeletal muscle vasodilation during exercise in CKD patients, which may contribute to exercise intolerance. Normally, there is blunting of sympathetic mediated vasoconstriction in exercising muscle to allow for steady blood supply to exercising muscles. This phenomenon is called functional sympatholysis. Functional sympatholysis is impaired by increases in reactive oxygen specie and may be impaired in CKD.

Experiments will be performed on 2 groups of subjects 1) Normal kidney function (eGFR>90) 2) Stage 2-3 CKD (eGFR 30-89). VAsoactive medications will be held for 72 hours before study. All participants will attend a baseline study visit, which will include a physical examination, a medical history review, vital sign measurements, and blood collection. Muscle nerve activity and muscle oxygenation will be measured while the subjects perform hand grip exercise at 30% maximum voluntary contraction with and without lower body negative pressure (- 20 mmHg). Muscle blood flow will be measured before and after hand grip exercises. CKD subjects will then be randomized to exercise training (to squeeze a tennis ball repeatedly for at least 30 min/day) or no exercise training for 28 days. Procedures in baseline visit will be repeated followed by cross over to alternate group for 28 days followed by repeat of baseline procedures. Blood flow, muscle oxygenation and muscle nerve activity will be compared between CKD and normal subjects as well as before and after exercise training for CKD subjects.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 32
• Est. completion date: March 18, 2021
• Est. primary completion date: March 18, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Normotensive adults

• CKD 2-3

Exclusion Criteria:

• Blood Pressure =140/90

• eGFR >60ml/min/1.73 m2 or eGFR <30ml/min/1.73 m2

• Any evidence of cardiopulmonary disease, left ventricular hypertrophy or systolic dysfunction by echocardiography.

• Diabetes mellitus or other systemic illness

• Pregnancy

• Any history of substance abuse or current cigarette use

• Any history of psychiatric illness

• History of malignancy

Related Conditions & MeSH terms

• Chronic Kidney Disease
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Behavioral:
• Forearm exercise training
Subjects will be asked to squeeze a tennis ball repeatedly for at least 30 min/day for 28 days at an approximate rate of 20 squeezes/min.

Locations

Country	Name	City	State
United States	University of Texas Southwestern Medical Center at Dallas	Dallas	Texas

Sponsors (1)

Lead Sponsor	Collaborator
University of Texas Southwestern Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (10)

Adams GR, Vaziri ND. Skeletal muscle dysfunction in chronic renal failure: effects of exercise. Am J Physiol Renal Physiol. 2006 Apr;290(4):F753-61. Review. — View Citation

Bradley JR, Anderson JR, Evans DB, Cowley AJ. Impaired nutritive skeletal muscle blood flow in patients with chronic renal failure. Clin Sci (Lond). 1990 Sep;79(3):239-45. — View Citation

Hansen J, Sander M, Thomas GD. Metabolic modulation of sympathetic vasoconstriction in exercising skeletal muscle. Acta Physiol Scand. 2000 Apr;168(4):489-503. Review. — View Citation

Kumar S, Seward J, Wilcox A, Torella F. Influence of muscle training on resting blood flow and forearm vessel diameter in patients with chronic renal failure. Br J Surg. 2010 Jun;97(6):835-8. doi: 10.1002/bjs.7004. — View Citation

Mizuno M, Iwamoto GA, Vongpatanasin W, Mitchell JH, Smith SA. Exercise training improves functional sympatholysis in spontaneously hypertensive rats through a nitric oxide-dependent mechanism. Am J Physiol Heart Circ Physiol. 2014 Jul 15;307(2):H242-51. d — View Citation

Moore GE, Painter PL, Brinker KR, Stray-Gundersen J, Mitchell JH. Cardiovascular response to submaximal stationary cycling during hemodialysis. Am J Kidney Dis. 1998 Apr;31(4):631-7. — View Citation

Paglialonga F, Lopopolo A, Scarfia RV, Galli MA, Consolo S, Brivio A, Grassi MR, Salera S, Edefonti A. Correlates of exercise capacity in pediatric patients on chronic hemodialysis. J Ren Nutr. 2013 Sep;23(5):380-6. doi: 10.1053/j.jrn.2013.04.006. Epub 20 — View Citation

Piantadosi CA, Hemstreet TM, Jöbsis-Vandervliet FF. Near-infrared spectrophotometric monitoring of oxygen distribution to intact brain and skeletal muscle tissues. Crit Care Med. 1986 Aug;14(8):698-706. — View Citation

Sakkas GK, Ball D, Mercer TH, Sargeant AJ, Tolfrey K, Naish PF. Atrophy of non-locomotor muscle in patients with end-stage renal failure. Nephrol Dial Transplant. 2003 Oct;18(10):2074-81. — View Citation

Vongpatanasin W, Wang Z, Arbique D, Arbique G, Adams-Huet B, Mitchell JH, Victor RG, Thomas GD. Functional sympatholysis is impaired in hypertensive humans. J Physiol. 2011 Mar 1;589(Pt 5):1209-20. doi: 10.1113/jphysiol.2010.203026. Epub 2011 Jan 4. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in muscle oxygenation	Tissue oxygenation will be recorded using Near-infrared spectroscopy (NIRS)	After 28 days
Secondary	Change in Forearm vascular conductance (FVC)	Doppler ultrasonography to measure blood flow	After 28 days
Secondary	Change in plasma isoprostanes	Plasma isoprostanes will be used as a measure of oxidative stress	After 28 days
Secondary	Change in muscle sympathetic nerve activity (MSNA)	MSNA will be measured using tiny tungsten wire inserted into the common peroneal nerve below fibular head.	After 28 days