The Effects of Dietary Nitrate in Patients With Hypertensive Kidney Injury

Обзор

The study aims to study the effects of diatery nitrate in patients with hypertension and hypertensive kidney injury. The study is a randomized, placebo-controlled, double-blinded crossover trial. 14-20 patients with hypertension and CKD I-III will be randomized to receive either nitrate or placebo delivered in the form of beetroot juice. Effect variables will be measured before and after a 2 week treatment. After a washout period of 14 days, the subjects are crossed over to the opposite treatment. The study is terminated by measuring effect variables after the second treatment period.

Подробное описание

AIM: We aim to investigate the mechanisms behind the cardiovascular and renal effect of nitrates in patients with hypertension and hypertensive kidney injury.

HYPOTHESIS: Dietary nitrate decreases BP and increases renal blood flow. This is independent of renal function or enhanced during low eGFR due to reduced renal clearance of nitrate.

METHODS: The study is a randomized, placebo-controlled, double-blinded crossover trial. 14-20 patients with hypertension and CKD I-III will be randomized to receive either nitrate or placebo delivered in the form of beetroot juice.

Effect variables will be measured before and after a 2 week treatment. After each treatment period effect variables will be measured, including include 24 hour bloodpressure measurment. Technetium(Tc)99m - Diethylenetriamine pentaacetate (DTPA) clearance and water based positron emission tomography computed tomography (PET/CT) is performed only after the intervention periods.

After a washout period of 14 days, the subjects are crossed over to the opposite treatment. The study is terminated by measuring effect variables after the second treatment period.

PERSPECTIVE: The knowledge gained from these studies can lead to improved dietary counselling, which is a promising approach in the treatment of hypertension.

Вмешательства

• Пищевая добавка Beetroot Juice - Active
  Intervention is beetroot juice ("Beet It concentrated beetroot juice shots", James White Drinks Ltd, Ipswich, England) The nitrate content of the juice is standardized. The dose of nitrate will be 70 ml/day corresponding to intake of 6.5 mmol/400 mg of nitrate.
• Пищевая добавка Beetroot juice placebo
  The placebo beetroot juice is a corresponding nitrate free beetroot juice, obtained from the manufacturer ("Beet It nitrate depleted shots", James White Drinks Ltd, Ipswich, England.). The placebo juice appears identical to the nitrate containing juice regarding color and taste.

Первичные конечные точки

• Changes in 24 h systolic blood pressure [Срок оценки: Measured on day 1 and day 15 of the intervention period (This represents baseline and after conclusion of each intervention period)]

Вторичные конечные точки (12)

• Diastolic blood pressure [Срок оценки: Measured on day 1 and day 15 of the intervention period (This represents baseline and after conclusion of each intervention period)]
• Heart rate [Срок оценки: Measured on 1 and day 15 of the intervention period (This represents baseline and after conclusion of each intervention period)]
• Pulsewave velocity [Срок оценки: Measured on day 1 and day 15 of the intervention period (This represents baseline and after conclusion of each intervention period)]
• Augmentation index [Срок оценки: Measured on day 1 and day 15 of the intervention period (This represents baseline and after conclusion of each intervention period)]
• Vascular resistance [Срок оценки: Measured on day 1 and day 15 of the intervention period (This represents baseline and after conclusion of each intervention period)]
• Reflection index [Срок оценки: Measured on day 1 and day 15 of the intervention period (This represents baseline and after conclusion of each intervention period)]
• Dipping status [Срок оценки: Measured on day 1 and day 15 of the intervention period (This represents baseline and after conclusion of each intervention period)]
• Blood pressure variability [Срок оценки: Measured on day 1 and day 15 of the intervention period (This represents baseline and after conclusion of each intervention period)]
• Unattended office blood pressure [Срок оценки: Measured on day 1 and day 15 of the intervention period (This represents baseline and after conclusion of each intervention period)]
• Renal Blood Flow (RBF) [Срок оценки: Measured on Day 15 of each intervention period]
• GFR [Срок оценки: Measured on Day 15 of each intervention period]
• Urine concentration of renal tubular transport proteins [Срок оценки: Measured on day 1 and day 15 of the intervention period (This represents baseline and after conclusion of each intervention period)]

Критерии участия

Критерии включения

• Hypertension, treated with a maximum of 2 antihypertensive drugs and unattended office BP < 150/95 mmHg at the screening visit, or newly diagnosed without antihypertensive treatment by 24-hour BP or home BP measurement (above 130/80 or 135/85 respectively), and unattended office BP < 160/100 mmHg.

• CKD I-III based on hypertensive kidney injury. Patients, who previously met the criteria for CKD I within the last 5 years, but no longer has proteinuria after relevant treatment, can also be included. Diagnosis of CKD I can be based on eGFR and either urine albumin/creatine ration or urine-dipstick test with presence of protein.
• Albumin/creatinine ratio < 500 mg/g
• eGFR > 30 ml/min/1,73m2
• Body Mass Index (BMI) ≤ 35 kg/m2
• Able to adhere to dietary regimen
• Fertile women must use safe contraception (oral contraceptive pill, hormonal or copper intrauterine device, vaginal ring, contraceptive implant, transdermal contraceptive patch or contraceptive injections) or abstinence. Excluded from this are postmenopausal woman without menstrual bleeding for at least 12 months before inclusion, surgically sterilized women and women with surgically sterilized partner.

Критерии исключения

• • Diagnosis of heart failure, NYHA II-IV

• Diagnosis of liver failure
• Diabetes mellitus (all types)
• Current malignant disease (other than non-melanoma skin cancer)
• Indicators of other aetiologies of CKD than hypertensive kidney injury, e.g. through kidney biopsy or biochemistry.
• Previous kidney transplant recipient
• History of stroke or transient cerebral ischemic attack
• Current indication of untreated cardiovascular disease, e.g. planned work-up for ischemia.
• History of myocardial infarction, apart from non-STEMI more than 1 year prior to the study, if the subject is currently revascularized and relevantly medicated.

Organic nitrate treatment Diagnosed secondary hypertension other than renal parenchymal hypertension (i.e. renal artery stenosis, primary hyperaldosteronism, low renin hypertension etc.)

• Pregnancy or lactation
• Alcohol abuse (intake above the recommended guidelines from Danish Health Authorities)
• Conditions treated with medication that investigator finds may interfere with the effect parameters, and cannot be discontinued during the trial (e.g. atrial fibrillation treated with betablockers)
• If, according to the investigator's assessment, the participant is considered unsuitable to participate.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Дания · 1 центр

• University Clinic in Nephrology and Hypertension, Gødstrup Regional Hospital and Aarhus Un — Herning

Идентификаторы

NCT: NCT07290842 · KTM-1-2025

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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