Chronotherapy Versus Conventional BP Control to Correct Abnormal Circadian BP Pattern in Kidney Transplant Recipients

Kidney Transplant Recipient Clinical Trial

Official title:

Randomized Trial to Explore the Effect of Chronotherapy Versus Conventional BP Control to Correct Abnormal Circadian BP Pattern and Improve Allograft Function in Kidney Transplant Recipients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01093703
• Other study ID #: 08-005049
• Status: Completed
• Phase: N/A
• First received: March 24, 2010
• Last updated: May 28, 2013
• Start date: December 2008
• Est. completion date: November 2012

Study information

• Verified date: May 2013
• Source: Mayo Clinic
• 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 is to identify and manage factors related to blood pressure control that impact organ function and survival in kidney transplant recipients. Loss of the circadian (relating to a 24-hour rhythm) blood pressure pattern is common in kidney transplant recipients and is associated with poor allograft kidney function. It is still unclear if restoring the normal day-night blood pressure (BP) pattern will translate into better allograft outcome. Although studies in patients with and without chronic kidney disease indicate that restoration of the normal nocturnal (night) dipping in BP is possible by changing the timing of the BP medications to cover the overnight period (chronotherapy), this has not been tested in kidney transplant patients.

Description:

The challenge in kidney transplantation is to identify and manage factors that impact allograft function and survival. Loss of the circadian blood pressure pattern is common in kidney transplant recipients and is associated with poor allograft kidney function. Nevertheless, it is unclear if restoring the normal day-night BP pattern will translate into better allograft outcome. Although studies in patients with and without chronic kidney disease indicate that restoration of the normal nocturnal dipping in BP is possible by changing the timing of the BP medications to cover the overnight period (chronotherapy), this has not been tested in kidney transplant patients. This exploratory study is driven by the hypothesis that chronotherapy will restore the normal circadian BP pattern and will translate into better allograft function and into lower LVM 1-year from transplantation.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 99
• Est. completion date: November 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Recipient of a kidney transplant.

• Age=18 years.

• Stable allograft function.

• Ability to give informed consent.

Exclusion Criteria:

• Multiorgan transplant recipients.

• Kidney transplant recipients with poor allograft function.

• Documented history of obstructive sleep apnea.

Study Design

Allocation: Randomized, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Blood Pressure Control
• Kidney Transplant Recipient

Intervention

Other:
• Medication Adjustment
Awake SBP=135/85mmHg and patient is on once daily medications: Switch BP medications to pm period. Awake SBP SBP=135/85mmHg and patient is on bid medications (e.g. metoprolol bid): Increase pm dose of the medication. If medication is already is at maximal dose or there is contraindication for increasing the dose (e.g. bradycardia), add another BP medicine in the evening time. Awake SBP=135/85mmHg and patient is not on anti-hypertensive medications: Add BP medication at the pm period. Awake SBP>135/85mmHg: increase dose of antihypertensive medications or add more medications. All medications to be given in the evening time.

Locations

Country	Name	City	State
United States	Mayo Clinic	Jacksonville	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Mayo Clinic

Country where clinical trial is conducted

United States, 

References & Publications (24)

Agarwal R, Andersen MJ. Prognostic importance of ambulatory blood pressure recordings in patients with chronic kidney disease. Kidney Int. 2006 Apr;69(7):1175-80. — View Citation

Clement DL, De Buyzere ML, De Bacquer DA, de Leeuw PW, Duprez DA, Fagard RH, Gheeraert PJ, Missault LH, Braun JJ, Six RO, Van Der Niepen P, O'Brien E; Office versus Ambulatory Pressure Study Investigators. Prognostic value of ambulatory blood-pressure recordings in patients with treated hypertension. N Engl J Med. 2003 Jun 12;348(24):2407-15. — View Citation

Covic A, Gusbeth-Tatomir P, Mardare N, Buhaescu I, Goldsmith DJ. Dynamics of the circadian blood pressure profiles after renal transplantation. Transplantation. 2005 Nov 15;80(9):1168-73. — View Citation

Davidson MB, Hix JK, Vidt DG, Brotman DJ. Association of impaired diurnal blood pressure variation with a subsequent decline in glomerular filtration rate. Arch Intern Med. 2006 Apr 24;166(8):846-52. Erratum in: Arch Intern Med. 2006 Aug 14-28;166(15):1619. — View Citation

Gali B, Whalen FX Jr, Gay PC, Olson EJ, Schroeder DR, Plevak DJ, Morgenthaler TI. Management plan to reduce risks in perioperative care of patients with presumed obstructive sleep apnea syndrome. J Clin Sleep Med. 2007 Oct 15;3(6):582-8. — View Citation

Haydar AA, Covic A, Jayawardene S, Agharazii M, Smith E, Gordon I, O'Sullivan H, Goldsmith DJ. Insights from ambulatory blood pressure monitoring: diagnosis of hypertension and diurnal blood pressure in renal transplant recipients. Transplantation. 2004 Mar 27;77(6):849-53. — View Citation

Hermida RC, Ayala DE, Calvo C, López JE, Mojón A, Fontao MJ, Soler R, Fernández JR. Effects of time of day of treatment on ambulatory blood pressure pattern of patients with resistant hypertension. Hypertension. 2005 Oct;46(4):1053-9. Epub 2005 Aug 8. — View Citation

Hermida RC, Ayala DE, Calvo C. Administration-time-dependent effects of antihypertensive treatment on the circadian pattern of blood pressure. Curr Opin Nephrol Hypertens. 2005 Sep;14(5):453-9. Review. — View Citation

Hermida RC, Ayala DE, Fernández JR, Calvo C. Chronotherapy improves blood pressure control and reverts the nondipper pattern in patients with resistant hypertension. Hypertension. 2008 Jan;51(1):69-76. Epub 2007 Oct 29. — View Citation

Hermida RC, Calvo C, Ayala DE, López JE. Decrease in urinary albumin excretion associated with the normalization of nocturnal blood pressure in hypertensive subjects. Hypertension. 2005 Oct;46(4):960-8. Epub 2005 Sep 6. — View Citation

Kapa S, Sert Kuniyoshi FH, Somers VK. Sleep apnea and hypertension: interactions and implications for management. Hypertension. 2008 Mar;51(3):605-8. doi: 10.1161/HYPERTENSIONAHA.106.076190. Epub 2008 Jan 28. Review. — View Citation

Kasiske BL, Anjum S, Shah R, Skogen J, Kandaswamy C, Danielson B, O'Shaughnessy EA, Dahl DC, Silkensen JR, Sahadevan M, Snyder JJ. Hypertension after kidney transplantation. Am J Kidney Dis. 2004 Jun;43(6):1071-81. — View Citation

Khot UN, Binkley PF, Haas GJ, Starling RC. Prospective study of the circadian pattern of blood pressure after heart transplantation. J Heart Lung Transplant. 1996 Apr;15(4):350-9. — View Citation

Logan AG, Tkacova R, Perlikowski SM, Leung RS, Tisler A, Floras JS, Bradley TD. Refractory hypertension and sleep apnoea: effect of CPAP on blood pressure and baroreflex. Eur Respir J. 2003 Feb;21(2):241-7. — View Citation

Lurbe E, Redon J, Kesani A, Pascual JM, Tacons J, Alvarez V, Batlle D. Increase in nocturnal blood pressure and progression to microalbuminuria in type 1 diabetes. N Engl J Med. 2002 Sep 12;347(11):797-805. — View Citation

Mange KC, Cizman B, Joffe M, Feldman HI. Arterial hypertension and renal allograft survival. JAMA. 2000 Feb 2;283(5):633-8. — View Citation

Minutolo R, Gabbai FB, Borrelli S, Scigliano R, Trucillo P, Baldanza D, Laurino S, Mascia S, Conte G, De Nicola L. Changing the timing of antihypertensive therapy to reduce nocturnal blood pressure in CKD: an 8-week uncontrolled trial. Am J Kidney Dis. 2007 Dec;50(6):908-17. — View Citation

Opelz G, Döhler B; Collaborative Transplant Study. Improved long-term outcomes after renal transplantation associated with blood pressure control. Am J Transplant. 2005 Nov;5(11):2725-31. — View Citation

Pennestri MH, Montplaisir J, Colombo R, Lavigne G, Lanfranchi PA. Nocturnal blood pressure changes in patients with restless legs syndrome. Neurology. 2007 Apr 10;68(15):1213-8. — View Citation

Shimada K, Kawamoto A, Matsubayashi K, Nishinaga M, Kimura S, Ozawa T. Diurnal blood pressure variations and silent cerebrovascular damage in elderly patients with hypertension. J Hypertens. 1992 Aug;10(8):875-8. — View Citation

Taler SJ, Textor SC, Canzanello VJ, Wilson DJ, Wiesner RH, Krom RA. Loss of nocturnal blood pressure fall after liver transplantation during immunosuppressive therapy. Am J Hypertens. 1995 Jun;8(6):598-605. — View Citation

Toprak A, Koc M, Tezcan H, Ozener IC, Oktay A, Akoglu E. Night-time blood pressure load is associated with higher left ventricular mass index in renal transplant recipients. J Hum Hypertens. 2003 Apr;17(4):239-44. — View Citation

Verdecchia P, Porcellati C, Schillaci G, Borgioni C, Ciucci A, Battistelli M, Guerrieri M, Gatteschi C, Zampi I, Santucci A, Santucci C, Reboldi G, et al. Ambulatory blood pressure. An independent predictor of prognosis in essential hypertension. Hypertension. 1994 Dec;24(6):793-801. Erratum in: Hypertension 1995 Mar;25(3):462. — View Citation

Wadei HM, Amer H, Taler SJ, Cosio FG, Griffin MD, Grande JP, Larson TS, Schwab TR, Stegall MD, Textor SC. Diurnal blood pressure changes one year after kidney transplantation: relationship to allograft function, histology, and resistive index. J Am Soc Nephrol. 2007 May;18(5):1607-15. Epub 2007 Apr 4. — View Citation

* Note: There are 24 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent drop in mean SBP at night-time compared to mean SBP in day-time		1 year	No
Primary	Glomerular filtration rate		1 year	No
Secondary	Awake mean SBP		1 year	No
Secondary	Presence of abnormal circadian BP pattern in recipients on steroid free and CIN free IS		1 year	No
Secondary	Change in LVM		1 year	No
Secondary	Urinary microalbumin excretion		4 months & 1 year	No
Secondary	Long term renal function		2 years	No
Secondary	Cardiovascular events (stroke, heart failure, myocardial infarction)		2 years	No

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