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

NCT ID: NCT02664519

Last Updated: 2021-03-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

NA

Total Enrollment

32 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-01-31

Study Completion Date

2021-03-18

Brief Summary

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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

Detailed Description

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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.

Conditions

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Chronic Kidney Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Exercise training followed by no exercise training

CKD subjects will 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.

Group Type EXPERIMENTAL

Forearm exercise training

Intervention Type BEHAVIORAL

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.

No exercise training followed by exercise training

CKD subjects will 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.

Group Type EXPERIMENTAL

Forearm exercise training

Intervention Type BEHAVIORAL

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.

Normal Control

Control subjects without CKD will undergo baseline assessment as above.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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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.

Intervention Type BEHAVIORAL

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of Texas Southwestern Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Wanpen Vongpatanasin

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Wanpen Vongpatanasin, MD

Role: PRINCIPAL_INVESTIGATOR

UT Southwestern Medical Center

Locations

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University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, United States

Site Status

Countries

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United States

References

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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. doi: 10.1053/ajkd.1998.v31.pm9531179.

Reference Type RESULT
PMID: 9531179 (View on PubMed)

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. doi: 10.1152/ajprenal.00296.2005.

Reference Type RESULT
PMID: 16527920 (View on PubMed)

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 2013 Jun 22.

Reference Type RESULT
PMID: 23800461 (View on PubMed)

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. doi: 10.1042/cs0790239.

Reference Type RESULT
PMID: 2169372 (View on PubMed)

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. doi: 10.1093/ndt/gfg325.

Reference Type RESULT
PMID: 13679483 (View on PubMed)

Hansen J, Sander M, Thomas GD. Metabolic modulation of sympathetic vasoconstriction in exercising skeletal muscle. Acta Physiol Scand. 2000 Apr;168(4):489-503. doi: 10.1046/j.1365-201x.2000.00701.x.

Reference Type RESULT
PMID: 10759586 (View on PubMed)

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.

Reference Type RESULT
PMID: 21224235 (View on PubMed)

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. doi: 10.1152/ajpheart.00103.2014. Epub 2014 May 9.

Reference Type RESULT
PMID: 24816260 (View on PubMed)

Piantadosi CA, Hemstreet TM, Jobsis-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. doi: 10.1097/00003246-198608000-00007.

Reference Type RESULT
PMID: 3013501 (View on PubMed)

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.

Reference Type RESULT
PMID: 20309951 (View on PubMed)

Other Identifiers

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STU 092015-005

Identifier Type: -

Identifier Source: org_study_id

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