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

December 10, 2014 updated by: Ho Jun Chin, Seoul National University Bundang Hospital

Effects of Low Sodium Intake on the Anti-proteinuric Efficacy of Olmesartan in Hypertensive Patients With Albuminuria Through Open-label Randomized Trial

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

  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.

Study Type

Interventional

Enrollment (Actual)

269

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Korea, Republic of
      • Seoul, Korea, Republic of, 110744
        • Seoul National University Hospital
      • Seoul, Korea, Republic of, 137701
        • Seoul St. Mary's Hospital
      • Seoul, Korea, Republic of, 134727
        • Kyung Hee University
      • Seoul, Korea, Republic of, 143729
        • Konkuk University School of Medicine
      • Seoul, Korea, Republic of, 156707
        • SMG-SNU Boramae Medical Center
    • Kyeong ki
      • Seongnam, Kyeong ki, Korea, Republic of, 463787
        • Seoul National University Bundang Hospital
    • Kyeongki
      • Ilsan, Kyeongki, Korea, Republic of, 410773
        • DongGuk University ilsan Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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")
Behavioral: 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.
Other Names:
  • low salt diet
  • Angiotensin II converting enzyme
  • albuminuria
  • chronic kidney disease
No Intervention: Conventional diet group
Education for low salt diet will be conducted as in office with brief communication with a patient and a physician.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
∆Albuminuria by 24-hour Urine Protein Excretion
Time Frame: changes from week 8 at week 16 (week 8 - week 16)

Change in albuminuria as a 24-hour urine protein excretion by intensive education of low salt diet during taking olmesartan

*In outcome measure data table, the 24-hour urine collection at 16th week was omitted in 3 out of 245 patients (1 for intensive education group and 2 for conventional education group). Values of each study week were "mean" of all participants on specific study week, but "∆albuminuria (week 8 - week 16)" value was "mean" of ∆ values of "8 weeks-16 weeks" in each individuals. Therefore, values of 3 patients were excluded in "mean of ∆albuminuria (week 8 - week 16)". That's why simple subtraction (week 8 - week 16) of values are not matched with the data.
changes from week 8 at week 16 (week 8 - week 16)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
∆Hemoglobin (0 Week - 16 Weeks)
Time Frame: 0 week, 16 weeks
The change of hemoglobin after prescription of Olmesartan
0 week, 16 weeks
Na Excretion Change in 24 Hour-urine Collection Between Weeks 8 and 16
Time Frame: week 8 and week 16
Change of sodium excretion rate in 24 hour-urine collection by intensive education for low salt diet at week 16
week 8 and week 16
Systolic and Diastolic Blood Pressure Change Between Weeks 8 and 16
Time Frame: week 8 and week 16
Change in Systolic and Diastolic Blood Pressure from Week 8 to Week 16 in the Intensive Education Group compared to the Conventional Education Group
week 8 and week 16

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Seoul National University Bundang Hospital

Collaborators

Daiichi Sankyo, Inc.
Daewoong Pharmaceutical Co. LTD.

Investigators

  • Principal Investigator: Ho Jun Chin, PhD, Seoul National University Bundang Hospital
  • Study Chair: Chun-Soo Lim, PhD, SMG-SNU Boramae Medical Center
  • Principal Investigator: Dong Ki Kim, PhD, Seoul National University Hospital
  • Principal Investigator: Suhnggwon Kim, PhD, Seoul National University Hospital
  • Principal Investigator: Bum Soon Choi, PhD, Seoul St. Mary's Hospital
  • Principal Investigator: Sang-Ho Lee, PhD, Kyunghee University
  • Principal Investigator: Jung-Hwan Park, PhD, Konkuk University
  • Principal Investigator: Sung Joon Shin, PhD, DongGuk University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2012

Primary Completion (Actual)

June 1, 2013

Study Completion (Actual)

October 1, 2013

Study Registration Dates

First Submitted

February 24, 2012

First Submitted That Met QC Criteria

March 9, 2012

First Posted (Estimate)

March 13, 2012

Study Record Updates

Last Update Posted (Estimate)

December 18, 2014

Last Update Submitted That Met QC Criteria

December 10, 2014

Last Verified

December 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • B-1112/142-008

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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