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UMIN ID:

Recruitment status Enrolling by invitation
Unique ID issued by UMIN UMIN000002591
Receipt No. R000003165
Scientific Title Intrarenal activation of renin-angiotensin system impairs circadian blood pressure rhythm.
Date of disclosure of the study information 2009/10/16
Last modified on 2017/11/03

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Basic information
Public title Intrarenal activation of renin-angiotensin system impairs circadian blood pressure rhythm.
Acronym Intrarenal AGT and non-dipper BP rhythm
Scientific Title Intrarenal activation of renin-angiotensin system impairs circadian blood pressure rhythm.
Scientific Title:Acronym Intrarenal AGT and non-dipper BP rhythm
Region
Japan

Condition
Condition Chronic kidney disease (CKD)
Classification by specialty
Cardiology Nephrology
Classification by malignancy Others
Genomic information NO

Objectives
Narrative objectives1 Kidneys play an important role in determining the circadian rhythm of BP. We have postulated that reduced renal capacity to excrete sodium into urine causes nocturnal elevation of blood pressure (BP), ie, nondippers, to compensate for diminished daytime natriuresis by enhancing pressure natriuresis during sleep. Furthermore, we had reported that not only in patients with reduced glomerular filtration rate (GFR), but also in patients with preserved GFR, such as diabetes mellitus or metabolic syndrome, renal capacity to excrete sodium into urine is impaired by enhanced tubular sodium reabsorption.
We also have reported that olmesartan, angiotensin II type 1 receptor blocker (ARB), could restore the circadian rhythms of BP and natriuresis from nondipper to dipper patterns in CKD, as seen with diuretics and sodium restriction, possibly by enhancing daytime sodium excretion. The more circadian rhythm was impaired at baseline, the more the ARB restored night-time BP fall.
On the other hand, Angiotensin (Ang) II, especially locally produced in the kidney, is one of the most powerful simulators of sodium-reabsorption at the various sites all the way from proximal tubule to the collecting ducts, and ARB has the possibility to suppress these sodium reabsorptions. Recently, urinary excretion of angiotensinogen (AGT), as well as AGT expression in the renal proximal tubules, has been proved to be useful marker of the intrarenal activation of renin-angiotensin system (RAS). In this study we investigate whether olmesartan can restore circadian BP rhythm more effectively in patients with activated intrarenal RAS leading to enhanced sodium reabsorption.
Basic objectives2 Pharmacodynamics
Basic objectives -Others
Trial characteristics_1 Confirmatory
Trial characteristics_2 Pragmatic
Developmental phase Not applicable

Assessment
Primary outcomes The primary purpose of this study is to investigate whether there is a positive relationship between the intrarenal activation of renin-angiotensin system (RAS), represented by Angiotensinogen (AGT) expression in the renal-biopsy specimens or urinary excretion of AGT, and night/day ratio of blood pressure, natriuresis or albuminuria, and whether the more intrarenal RAS is activated at baseline, the more the reduction in night/day ratio of blood pressure, natriuresis or albuminuria is.
Key secondary outcomes The secondary purpose of this study is to evaluate whether night/day ratio of urinary excretion rate of AGT shows positive relationship with night/day ratio of blood pressure, natriuresis or albuminuria, and negative one with creatinine clearance and to investigate, in case that the second biopsy is performed, whether the more AGT expression is reduced, the more night/day ratio of blood pressure, natriuresis or albuminuria is decreased. IHC for pro-renin and ACE2 expression is to be studied.

Base
Study type Interventional

Study design
Basic design Single arm
Randomization Non-randomized
Randomization unit
Blinding Open -no one is blinded
Control Uncontrolled
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms 1
Purpose of intervention Treatment
Type of intervention
Medicine
Interventions/Control_1 After the baseline study, participants received single daily olmesartan in the morning (daily 20mg for 8 weeks). The dosage of olmesartan was increased to the highest dose tolerated, unless their systolic BP decreased below 90mmHg or patients felt postural dizziness. If these symptoms occurred, dosages of olmesartan were reduced.
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit
15 years-old <=
Age-upper limit

Not applicable
Gender Male and Female
Key inclusion criteria Eligibility criteria include the following: age of 15 years or more; hospitalized in Nagoya City University hospital to undergo a renal biopsy ; diagnosed as having chronic kidney disease (CKD) based on K/DOQI criteria (either kidney damage or glomerular filtration of <60 mL/min/1.73m2 for 3 months or more); and written informed consent was obtained.
Key exclusion criteria Exclusion criteria are as follows; use of inhibitors of renin-angiotensin system or diuretics 1 month before enrollment; specific contraindication to a study drug; presence or possibility of pregnancy; HbA1c of 9.0 % or above; serious liver damage (GOT >100, or GPT >85); secondary hypertension; accelerated or malignant hypertension (progressive renal dysfunction with diastolic BP of >120-130 mmHg); serious congestive heart failure, coronary heart disease, arrhythmia, or systemic diseases; or any reason for ineligibility suggested by the attending doctor.
Target sample size 40

Research contact person
Name of lead principal investigator
1st name
Middle name
Last name Michio Fukuda
Organization Nagoya City University Graduate School of Medical Sciences
Division name Department of Cardio-Renal Medicine and Hypertension
Zip code
Address Mizuho-ku, Nagoya 467-8601, Japan
TEL +81-52-853-8221
Email m-fukuda@med.nagoya-cu.ac.jp

Public contact
Name of contact person
1st name
Middle name
Last name Michio Fukuda
Organization Nagoya City University Graduate School of Medical Sciences
Division name Department of Cardio-Renal Medicine and Hypertension
Zip code
Address Mizuho-ku, Nagoya 467-8601, Japan
TEL +81-52-853-8221
Homepage URL
Email m-fukuda@med.nagoya-cu.ac.jp

Sponsor
Institute Department of Cardio-Renal Medicine and Hypertension, Nagoya City University Graduate School of Medical Sciences
Institute
Department

Funding Source
Organization None
Organization
Division
Category of Funding Organization Self funding
Nationality of Funding Organization

Other related organizations
Co-sponsor Department of Physiology and Hypertension and Renal Center of Excellence, Tulane University Health Sciences Center
Name of secondary funder(s)

IRB Contact (For public release)
Organization
Address
Tel
Email

Secondary IDs
Secondary IDs NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions 名古屋市立大学 (愛知県); Nagoya City University Hospital

Other administrative information
Date of disclosure of the study information
2009 Year 10 Month 16 Day

Related information
URL releasing protocol
Publication of results Unpublished

Result
URL related to results and publications
Number of participants that the trial has enrolled
Results
data acquirement is not completed.
Twenty patients has been enrolled.
Results date posted
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics
Participant flow
Adverse events
Outcome measures
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status Enrolling by invitation
Date of protocol fixation
2009 Year 09 Month 02 Day
Date of IRB
Anticipated trial start date
2009 Year 09 Month 01 Day
Last follow-up date
2015 Year 02 Month 28 Day
Date of closure to data entry
2015 Year 12 Month 31 Day
Date trial data considered complete
2015 Year 12 Month 31 Day
Date analysis concluded
2015 Year 12 Month 31 Day

Other
Other related information

Management information
Registered date
2009 Year 10 Month 07 Day
Last modified on
2017 Year 11 Month 03 Day


Link to view the page
URL(English) https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000003165

Research Plan
Registered date File name

Research case data specifications
Registered date File name

Research case data
Registered date File name


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