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

Study Overview
=================
Brief 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.

Detailed 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.

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

Conditions
-----------------
Blood Pressure Control, Kidney Transplant Recipient

Intervention / Treatment
-----------------
* Other: Medication Adjustment


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Conventional Therapy<br>In the conventional therapy group, no medication changes other than the ones needed to achieve target awake average SBP will be undertaken. Time at which patients are taking their BP medications will be recorded. | |
| Active Comparator: Intensive Therapy<br>In the intensive therapy group, BP medications will be adjusted to both control awake average systolic BP to target and to cover the overnight period in an attempt to control nocturnal hypertension. | Other: Medication Adjustment<br>* 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.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent drop in mean SBP at night-time compared to mean SBP in day-time |  | 1 year | 
| Glomerular filtration rate |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Awake mean SBP |  | 1 year | 
| Presence of abnormal circadian BP pattern in recipients on steroid free and CIN free IS |  | 1 year | 
| Change in LVM |  | 1 year | 
| Urinary microalbumin excretion |  | 4 months & 1 year | 
| Long term renal function |  | 2 years | 
| Cardiovascular events (stroke, heart failure, myocardial infarction) |  | 2 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
kidney transplantation, hypertension, chronotherapy, graft function, circadian pattern