Effects of Low Sodium Intake on the Anti-proteinuric Efficacy in Hypertensive Patient With Olmesartan

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

269 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-02-29

Study Completion Date

2013-10-31

Brief Summary

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Purpose of this study

1. Intensive education for low salt diet will be enhance the anti-proteinuric effect of Olmesartan, a popular anti-hypertensive drug of angiotensin II receptor blocker, in Koreans compared to conventional prescription of medication.
2. Intensive education for low salt diet will decrease the amount of 24 hour-urine sodium excretion compared to control group, effectively.

Detailed Description

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1. Background

A. The chronic kidney disease (CKD) is the one of the main burden of chronic diseases and the prevalence of CKD is increasing in worldwide. In Korea, the prevalence of CKD was reported as 13.7% among urban Korean adults in 2008 by our study group.

B. It is well known the CKD is the most important risk factor to cardiovascular events, cardiovascular mortality, all cause-mortality, and hospitalization. The cost of the management for the CKD was high and it took 3.25% of all budgets for medical reimbursement in 2004 for all Koreans, which was ranked on the top of expenditure for single disease category.

C. The most popular risk factors to CKD progression are aging, obesity, hyperlipidemia, diabetes mellitus, hypertension, and proteinuria. The hypertension and proteinuria also cause the cardiovascular events and increase the mortality rate.

D. The inhibitors for renin-angiotensin aldosterone system, angiotensin II type I receptor blocker (ARB) and angiotensin converting enzyme inhibitor (ACEI), are well known medications to prevent cardiovascular events and renal functional deterioration to end stage renal disease(ESRD) in patients with hypertension, non-diabetic CKD, or diabetic nephropathy. One of the adverse events of ARB is the decrease of hemoglobin. Inoue et al reported the level of hemoglobin was decreased in amount of 0.45 ±0.89 g/dL after prescription of ARB and valsartan decreased the erythropoietin in 6 days after medication. The exact mechanism of decrease of hemoglobin by ARB was not fully verified but it is related to decrease effects of angiotensin II on aggravating hypoxia in the kidney and on the activation of hypoxia-inducible factor 1α (HIF1a) and then decrease the production of erythropoietin as in the report of Durmus et al. Considering that the relationships between ARB usage and decrease of proteinuria in transplanted kidney, between aggravation of hypoxia or HIF1a and CKD, and between ARB and the decrease of HIF1a or erythropoietin(EPO), we could postulate that the decrease of hemoglobin would not be a adverse effect of ARB to deteriorate patients' condition but a co-phenomenon of ARB's anti-RAS effect and a marker of ARB's effectiveness.

E. The anti-proteinuric effect of ARB is decreased by high salt intake. For example, ARB treatment without low salt intake decreased proteinuria by 30% in patients with proteinuria 2-10g/day compared to baseline value and addition of low salt diet to ARB treatment further decreased proteinuria up to 25%. But, using slow salt tablets, increase of daily intake of sodium diminished the anti-proteinuric effect of ARB in diabetic nephropathy.

F. The previous studies for the effect of ARB on proteinuria affected by sodium intake took the methods of controlled diet by researcher or using slow salt tablet but these method are not practical to adopt in real clinical practice.

G. The moderate and mild decrease of daily sodium intake which lower the daily excretion of sodium by 55 mEq/day had an effect of decrease of proteinuria by 11% in hypertensive patients.

H. The mean amount of sodium of Korean diets was reported as high as 208 mmol/day in Intersalt study, which is more than 11 g of salt. The recent reports also showed the trend of high salt-intake by Koreans.
2. Rationale So, It is worth to do this study because

* high salt intake is prevalent in Koreans,
* high salt diet diminishes the effect of ARB on proteinuria
* the methods used in previous studies were not suitable to apply to clinical practice,
* and there were no study to reveal the decrease of hemoglobin would the marker for the effect of ARB and not be a adverse event of ARB.
3. Objectives

1. Primary objective: The difference between amount of albuminuria after usage of Olmesartan and amount of albuminuria after prescription of Olmesartan with intensive diet education in intervention group is higher than the difference of albuminuria in control group.
2. Secondary objective:

Item 1: In all patients, Olmesartan decreases the albuminuria. Item 2: In all patients, the change of hemoglobin after prescription of Olmesartan is proportional to the change of albuminuria and serum erythropoietin.

Item 3: Intensive education for low salt diet induces the significant decrease of daily sodium excretion in Intervention group compared to control group.

Item 4: Intensive education for low salt diet induces the significant decrease of blood pressure in Intervention group compared to control group.
4. Study Flow

* Period

1. Washout period (-8 weeks;Point 0 to 0 weeks; Point 1)
2. Olmesartan Period ( 0 week; point 1 to 8 weeks; point 2)
3. Intervention period (8 week ; point 2 to 16 weeks; point 3)
* For patients with taking ACEI, other ARB, diuretics, or renin inhibitor, already; Initial wash-out period for 8 weeks, and then (point 1) prescription of Olmesartan 40 mg qd for 8 weeks, and then (point 2) allocation to Intensive group or control group for 8 weeks, and then the study will be over (point 3).
* For patients without taking ACEI, other ARB, diuretics, or renin inhibitor; For initial 8 weeks, adjust the blood pressures around 140/90 mmHg, and then (point 1) prescription of Olmesartan 40 mg qd for 8 weeks, and then (point 2) allocation to Intensive group or control group for 8 weeks, and then the study will be over (point 3).
* Blood pressure control Adjust the blood pressures around 140/90 mmHg with other hypertensive drugs except ACEI, other ARB, diuretics, or renin inhibitor during whole period.
* Intensive diet education:

For 8 weeks, dietitian will call patients to take the information according to pre-defined questionnaire, to check the daily diet habit and daily food taken, and to guide how to lessen sodium intake for 30 min at each call. The call will be done once a week for 8 weeks.

Conditions

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Hypertension Chronic Kidney Disease Microalbuminuria

Keywords

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hypertension Chronic kidney disease albuminuria low salt diet Angiotensin II receptor blocker

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Intensive education of low salt diet

For 8 weeks, dietitian will call patients to take the information according to pre-defined questionnaire, to check the daily diet habit and daily food taken, and to guide how to lessen sodium intake for 30 min at each call. The call will be done once a week for 8 weeks. (\*Intervention in this trial is the "intensity of education")

Group Type EXPERIMENTAL

Intensive education of low salt diet

Intervention Type BEHAVIORAL

For 8 weeks, dietitian will call patients to take the information according to pre-defined questionnaire, to check the daily diet habit and daily food taken, and to guide how to lessen sodium intake for 30 min at each call. The call will be done once a week for 8 weeks.

Conventional diet group

Education for low salt diet will be conducted as in office with brief communication with a patient and a physician.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Intensive education of low salt diet

For 8 weeks, dietitian will call patients to take the information according to pre-defined questionnaire, to check the daily diet habit and daily food taken, and to guide how to lessen sodium intake for 30 min at each call. The call will be done once a week for 8 weeks.

Intervention Type BEHAVIORAL

Other Intervention Names

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low salt diet Angiotensin II converting enzyme albuminuria chronic kidney disease

Eligibility Criteria

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Inclusion Criteria

* Aged 19 years or more and 75 years or less
* Hypertension patients: Patients whose blood pressure is 140/90mmHg and over, patients is newly diagnosed with hypertension or is prescribed antihypertensive medications.
* Hypertensive patients verified 2 times or more of albuminuria 30 mg/g cr or more in a spot urine sample with interval of 1 week or more in recent 6 months
* Estimated glomerular filtration rate (GFR) by Modification of Diet in Renal Disease (MDRD) equation 30 ml/min/1.73 m2 or more
* Patients who give written consent to this study by oneself

Exclusion Criteria

* Blood pressure more than 160/100 mmHg
* Pregnant
* Serum potassium level more than 5.5 mEq/L at screening period
* Patients with malignancy, acute cerebral infarction, acute myocardial infarction, unstable angina, percutaneous coronary arterial intervention (PCI), or coronary artery bypass graft (CABG) in recent 6 months
* Patients with diabetes mellitus
* Patients who have an allergy to Olmesartan
* Patients who were involved in other clinical trial in recent 1 month or are participated in screening period
* Patients taking medication(s) of corticosteroid or immunosuppressant in a screening period

Minimum Eligible Age

19 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Responsible Party

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Ho Jun Chin

Associate Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Role: PRINCIPAL_INVESTIGATOR

DongGuk University

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South Korea

Reference Type DERIVED

PMID: 37612109 (View on PubMed)

Other Identifiers

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B-1112/142-008

Identifier Type: -

Identifier Source: org_study_id

Effects of Low Sodium Intake on the Anti-proteinuric Efficacy in Hypertensive Patient With Olmesartan

Study Results

Basic Information

Brief Summary

Detailed Description

Conditions

Keywords

Study Design

Study Groups

Intensive education of low salt diet

Intensive education of low salt diet

Conventional diet group

Interventions

Intensive education of low salt diet

Other Intervention Names

Eligibility Criteria

Inclusion Criteria

Exclusion Criteria

Sponsors

Daiichi Sankyo

Daewoong Pharmaceutical Co. LTD.

Seoul National University Bundang Hospital

Responsible Party

Ho Jun Chin

Principal Investigators

Ho Jun Chin, PhD

Chun-Soo Lim, PhD

Dong Ki Kim, PhD

Suhnggwon Kim, PhD

Bum Soon Choi, PhD

Sang-Ho Lee, PhD

Jung-Hwan Park, PhD

Sung Joon Shin, PhD

Locations

Seoul National University Bundang Hospital

Dongguk University Ilsan Hospital

Seoul National University Hospital

Kyung Hee University

Seoul St. Mary's Hospital

Konkuk University School of Medicine

SMG-SNU Boramae Medical Center

Countries

References

McMahon EJ, Campbell KL, Bauer JD, Mudge DW, Kelly JT. Altered dietary salt intake for people with chronic kidney disease. Cochrane Database Syst Rev. 2021 Jun 24;6(6):CD010070. doi: 10.1002/14651858.CD010070.pub3.

Conley MM, McFarlane CM, Johnson DW, Kelly JT, Campbell KL, MacLaughlin HL. Interventions for weight loss in people with chronic kidney disease who are overweight or obese. Cochrane Database Syst Rev. 2021 Mar 30;3(3):CD013119. doi: 10.1002/14651858.CD013119.pub2.

Vogt L, Waanders F, Boomsma F, de Zeeuw D, Navis G. Effects of dietary sodium and hydrochlorothiazide on the antiproteinuric efficacy of losartan. J Am Soc Nephrol. 2008 May;19(5):999-1007. doi: 10.1681/ASN.2007060693. Epub 2008 Feb 13.

Intersalt: an international study of electrolyte excretion and blood pressure. Results for 24 hour urinary sodium and potassium excretion. Intersalt Cooperative Research Group. BMJ. 1988 Jul 30;297(6644):319-28. doi: 10.1136/bmj.297.6644.319.

Swift PA, Markandu ND, Sagnella GA, He FJ, MacGregor GA. Modest salt reduction reduces blood pressure and urine protein excretion in black hypertensives: a randomized control trial. Hypertension. 2005 Aug;46(2):308-12. doi: 10.1161/01.HYP.0000172662.12480.7f. Epub 2005 Jun 27.

Other Identifiers

B-1112/142-008