Volume,Sodium and Blood Pressure Management in HD

End Stage Renal Failure Clinical Trial

— VSBP  

Official title:

Fluid-Weight, Volume, Sodium, Blood Pressure Management in Hemodialysis by Limiting Intradialytic and Inter-dialytic Exposure to Sodium and Protocol-based Challenge of Post-dialysis Target Weight: A Pilot and Feasibility Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01766882
• Other study ID #: HUM00054879
• Status: Completed
• Phase: N/A
• First received: January 9, 2013
• Last updated: July 14, 2016
• Start date: September 2012
• Est. completion date: March 2016

Study information

• Verified date: July 2016
• Source: University of Michigan
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of this study to conduct a pilot, randomized trial in stable HD patients to evaluate the effect of gradual, step-wise reduction of post-hemodialysis target weight, combined with diligent dietary sodium restriction and reduction in dialysate sodium exposure on hydration/volume status and blood pressure (BP) control.

Description:

Fluid-weight management is critical for dialysis patients 1, 2. Previous clinical trials have not comprehensively addressed the application of a strategy combining both sodium restriction and a progressive, but gradual challenge of post dialysis target weight for BP and fluid-weight management in hemodialysis (HD). The investigators postulate that a protocolized, stepwise and gradual challenge of post-hemodialysis target weight when combined with diligent dietary sodium restriction <2000mg sodium/day, will lead to better hydration/volume status and BP control in HD patients. A randomized, two parallel arm trial (n=40) among HD patients is proposed, that compares this comprehensive strategy in one group versus 'usual' HD volume/hydration and BP management in the control group. The two primary outcomes are change in volume/hydration status (assessed by bioelectrical impedance analysis-BIA) and change in BP (pre-dialysis in-center readings, home self-monitored readings as well as 44-hour interdialytic BP). Secondary outcomes include change in target post-dialysis weight, slope of on-line relative plasma volume monitoring (using Crit-line monitors), utilization and change, if any, in antihypertensive regimen, change in interdialytic weight gain, objectively assessed salt-appetite, thirst score, frequency of intradialytic hypotension, cramps and duration of post-dialysis fatigue and recovery, time to achievement of dry weight and laboratory parameters (hemoglobin, albumin, brain natriuretic peptide-BNP, aldosterone and hsCRP). The trial will be 14-weeks in duration and will involve comprehensive assessment of study parameters at baseline, middle and end of the trial. It is anticipated that the trial will lead to the the development of a simple and practical approach for volume and BP control in HD patients that will subsequently need to be studied on a larger scale, i.e., a larger, multicenter study with hard endpoints of death and hospitalization.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: March 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• Stable adult HD patient (age 18-85 years)

• Usual in-center pre-dialysis systolic blood pressure of =130mmHg. For this purpose mean of pre-dialysis sitting blood pressures for the past one month prior to randomization will be applied for evaluation of inclusion criteria.

• Able and willing to adhere to study protocol

Exclusion Criteria:

• Recent acute illness (=1month)

• Recent hospitalization (=1month)

• Any psychological condition that could interfere with compliance with study protocol.

• Amputation of both lower limbs (due to interference with electric current for BIA measurement)

• Pacemaker, defibrillator, implantable pump, artificial joint, pins, plates or other types of metal objects in the body (other than dental fillings), if their presence interfere with appropriate measurements. In such patients consideration will be given to only doing the calf-BIA measurements and not the total body, at the discretion of the investigators.

• Use of any investigational product or device within 30 days prior to screening, or requirement for any investigational agent prior to completion of all scheduled study assessments.

• Pregnancy or lactation (pregnancy test will be applied only if the patient is in the reproductive age range).

• Any condition that, in the view of the PI, places the subject at high risk of poor treatment compliance or of not completing the study

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• End Stage Renal Failure
• Kidney Failure, Chronic
• Renal Insufficiency
• Renal Insufficiency, Chronic

Intervention

Behavioral:
• Lower sodium intervention
1. Lower sodium intervention: Dietary sodium restriction of =2.0 g/day or =85 mmol/day (approximately >180-200mmol/day in the average American diet). Sodium restriction will be implemented using intensive dietary counseling performed weekly by a registered study dietitian using the motivational interviewing technique. Lower dialysate sodium at 137 mmol/L, if perchance a different concentration of dialysate is used for the enrolled individual, although this is unlikely in both the UM associated units, where for some time now, dialysate concentration of 137 mmol/L is currently being used as standard practice. Investigators will ensure that this sodium concentration is indeed used for all study participants.

Other:
• Progressive Challenge to Post Dialysis Weight
The existing target post-HD weight will be progressively challenged by removing additional fluid in small increments, unless clinical evidence of volume depletion or hypotension precludes this challenge in the intervention arm. To avoid the occurrence of intradialytic hypotension, the ultrafiltration rate shall not exceed15 ml/kg/hour and post dialysis weight will not be reduced by more than 0.5 kg per dialysis session. In some patients, this may warrant prolongation of the treatment time to achieve lowering of target post dialysis weight, and this process of target weight reduction may need to continue up to and through the interim assessment phase (6-8 weeks).

Locations

Country	Name	City	State
United States	University Dialysis Unit	Ann Arbor	Michigan
United States	University of Michigan Dialyisis Unit	Livonia	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
University of Michigan	Renal Research Institute

Country where clinical trial is conducted

United States, 

References & Publications (16)

Aybal Kutlugün A, Erdem Y, Okutucu S, Yorgun H, Atalar E, Arici M. Effects of lowering dialysate sodium on flow-mediated dilatation in patients with chronic kidney disease. Nephrol Dial Transplant. 2011 Nov;26(11):3678-82. doi: 10.1093/ndt/gfr092. Epub 2011 Mar 18. — View Citation

Bots CP, Brand HS, Veerman EC, Valentijn-Benz M, Van Amerongen BM, Valentijn RM, Vos PF, Bijlsma JA, Bezemer PD, Ter Wee PM, Amerongen AV. Interdialytic weight gain in patients on hemodialysis is associated with dry mouth and thirst. Kidney Int. 2004 Oct;66(4):1662-8. — View Citation

Charra B. Fluid balance, dry weight, and blood pressure in dialysis. Hemodial Int. 2007 Jan;11(1):21-31. Review. — View Citation

Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001 Sep;16(9):606-13. — View Citation

Kurtz TW, Griffin KA, Bidani AK, Davisson RL, Hall JE; Subcommittee of Professional and Public Education of the American Heart Association. Recommendations for blood pressure measurement in humans and experimental animals. Part 2: Blood pressure measurement in experimental animals: a statement for professionals from the subcommittee of professional and public education of the American Heart Association council on high blood pressure research. Hypertension. 2005 Feb;45(2):299-310. Epub 2004 Dec 20. — View Citation

Manlucu J, Gallo K, Heidenheim PA, Lindsay RM. Lowering postdialysis plasma sodium (conductivity) to increase sodium removal in volume-expanded hemodialysis patients: a pilot study using a biofeedback software system. Am J Kidney Dis. 2010 Jul;56(1):69-76. doi: 10.1053/j.ajkd.2009.12.037. Epub 2010 Mar 19. — View Citation

Maruyama C. Improvement of Threshold-Dosage Salt Sensitivity Strips in Evaluating Reduced Salt Diets. The Japanese Journal of Nutrition and Dietetics 1988;46:211-6.

Maruyama C. On Salt Taste Sensitivity of Healthy Patients and Patients with High Blood Pressure (Part 2). The Japanese Journal of Nutrition and Dietetics 1990;48:267-71.

McCarley P. Patient empowerment and motivational interviewing: engaging patients to self-manage their own care. Nephrol Nurs J. 2009 Jul-Aug;36(4):409-13. — View Citation

Munoz Mendoza J, Bayes LY, Sun S, Doss S, Schiller B. Effect of lowering dialysate sodium concentration on interdialytic weight gain and blood pressure in patients undergoing thrice-weekly in-center nocturnal hemodialysis: a quality improvement study. Am J Kidney Dis. 2011 Dec;58(6):956-63. doi: 10.1053/j.ajkd.2011.06.030. Epub 2011 Aug 27. — View Citation

Nanovic L. Electrolytes and fluid management in hemodialysis and peritoneal dialysis. Nutr Clin Pract. 2005 Apr;20(2):192-201. Review. — View Citation

Pickering TG, Hall JE, Appel LJ, Falkner BE, Graves J, Hill MN, Jones DW, Kurtz T, Sheps SG, Roccella EJ; Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research. Recommendations for blood pressure measurement in humans and experimental animals: Part 1: blood pressure measurement in humans: a statement for professionals from the Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research. Hypertension. 2005 Jan;45(1):142-61. Epub 2004 Dec 20. — View Citation

Ritz E, Dikow R, Morath C, Schwenger V. Salt--a potential 'uremic toxin'? Blood Purif. 2006;24(1):63-6. Review. — View Citation

Sinha AD, Light RP, Agarwal R. Relative plasma volume monitoring during hemodialysis AIDS the assessment of dry weight. Hypertension. 2010 Feb;55(2):305-11. doi: 10.1161/HYPERTENSIONAHA.109.143974. Epub 2009 Dec 28. — View Citation

Urbina E, Alpert B, Flynn J, Hayman L, Harshfield GA, Jacobson M, Mahoney L, McCrindle B, Mietus-Snyder M, Steinberger J, Daniels S; American Heart Association Atherosclerosis, Hypertension, and Obesity in Youth Committee. Ambulatory blood pressure monitoring in children and adolescents: recommendations for standard assessment: a scientific statement from the American Heart Association Atherosclerosis, Hypertension, and Obesity in Youth Committee of the council on cardiovascular disease in the young and the council for high blood pressure research. Hypertension. 2008 Sep;52(3):433-51. doi: 10.1161/HYPERTENSIONAHA.108.190329. Epub 2008 Aug 4. — View Citation

Ware J, Snow K K, Kosnski M, Gandek B. SF-36 Health Survey: Manual and Interpretation Guide. Boston: Health Institute, 1993.

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Blood Pressure	Change in blood pressure (pre-dialysis in-center blood pressure readings, ABPM and home BP monitoring)	Pre-dialysis BP measure at Baseline, 6 Weeks and 12 weeks. ABPM measured at baseline and 12 Weeks. Home BP measure through out the 12week period on non-dialysis days	No
Secondary	Post-dialysis Weight	Change in target post-dialysis weight	12weeks	No
Secondary	Heart Rate	Change in heart rate	12 weeks	No
Secondary	Plasma Volume	Slope of relative plasma volume monitoring	12 Weeks	No
Secondary	Medication Use	Change in the utilization of antihypertensive medication ( number of medication and dose)	12 Weeks	No
Secondary	Interdialytic Weight gain	Change in the mid-week interdialytic weight gain	12 Weeks	No
Secondary	Intradialytic Hypotension	Frequency of intradialytic hypotension; defined as drop in systolic blood pressure associated with symptoms suggestive of low blood pressure such as lightheadedness, dizziness, sweating, etc., or decrease in intradialytic systolic blood pressure to less than 90 mmHg.	12 Weeks	Yes
Secondary	Salt Appetite	A measure of salt taste impairment and preference	Baseline, 6 week and 12 week	No
Secondary	Thirst Score	A measure of general thirst.	Baseline, 6 week, 12 weeks	No
Secondary	Post-dialysis fatigue	A measure of post-dialysis fatigue and recovery after each treatment session	Baseline, 6 Weeks & 12 Weeks	No
Secondary	Routine Labs	o Routine labs including CBC, renal panel, hsCRP and brain natriuretic peptide (BNP). Interdialytic urine collection for residual renal function (urea and creatinine clearance) estimation will be made. Blood and urine samples will be archived for later analysis for biomarkers such as asymmetric dimethyl arginine (ADMA), plasma aldosterone, and urinary neutrophil gelatinase-associated lipocalin (NGAL), respectively	Baseline and 12Week	No
Secondary	True Dry Weight	Time to achievement of true 'dry weight' (in the intervention arm only)	12 weeks	No
Secondary	Hydration Status	Change in hydration status, as measured by BIA, using whole body and segmental techniques.	12 weeks	No