Autosomal Dominant Polycystic Kidney, Hypertension, Endothelial Dysfunction
Conditions
Keywords
Autosomal Dominant Polycystic Kidney Disease, ADPKD, Beetroot juice, Hypertension, Nitrate supplementation, Nitric oxide
Brief summary
People with autosomal dominant polycystic kidney disease (ADPKD) develop high blood pressure and kidney disease. Previous studies have shown that a commonly occurring chemical, nitric oxide (NO), is reduced in ADPKD, and may contribute, in part, to high blood pressure in this condition. Nitrate is found in high concentrations naturally in beetroots, and increases NO. The aim of this study is to determine if beetroot juice reduces blood pressure in hypertensive people with ADPKD.
Interventions
DIETARY_SUPPLEMENTBeetroot juice
70mls beetroot juice (400mg nitrate) given daily for 4 weeks
DIETARY_SUPPLEMENTNitrate-depleted beetroot juice
70mls beetroot juice (nitrate-depleted) given daily for 4 weeks
Sponsors
Westmead Institute for Medical Research
Western Sydney Local Health District
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of Autosomal Dominant Polycystic Kidney Disease * Age \> 18 years old * Estimated Glomerular Filtration Rate (eGFR) \> 30 mL/min/1.73m2 * Treatment with at least one anti-hypertensive
Exclusion criteria
* Inability to provide Informed Consent * Labile, unstable, uncontrolled hypertension and/or changes in BP treatment 28 days prior to the screening visit * Non-compliance with study procedures and/or daily BP measurements during the screening period * Medical conditions or treatments that might interfere with the generation of NO metabolites or the primary endpoint (e.g. nitrate drugs; cigarette smoking; unwilling to stop using antiseptic mouthwash; severe, uncontrolled hypercholesterolemia; pregnancy or post-partum and lactating) * Any serious or other medical conditions that might interfere with follow-up or stability of blood pressure (e.g. current active malignancies; uncontrolled diabetes mellitus with elevated HbA1c \> 10%) * Dislike of taste of beetroot juice * Allergy to beetroot * Enrolled in other clinical trials
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Clinic Systolic and Diastolic Blood Pressure From Baseline to 4 Weeks (End of Study) | 4 weeks | Change in systolic and diastolic blood pressure over two time points - from readings taken at baseline (visit 1) compared with readings taken at 4 weeks (which was the end of the study; visit 3) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average Change in Daily Home Systolic and Diastolic Blood Pressure Per Week, Over 4 Weeks | 4 weeks | Reported change in blood pressure is average change per week, over 4 weeks |
| Urinary Albumin to Creatinine Ratio at Baseline and at 4 Weeks (End of Study) | 4 weeks | — |
| Change in Serum Nitric Oxide Metabolite Levels From Baseline to 4 Weeks (End of the Study) | 4 weeks | — |
| Change in Salivary Nitric Oxide Metabolite Levels From Baseline to 4 Weeks (End of the Study) | 4 weeks | — |
| Serum Asymmetric Dimethylarginine at Baseline and at 4 Weeks (End of the Study) | 4 weeks | Asymmetric dimethylarginine (ADMA) which is a recognized marker of endothelial dysfunction and inhibitor of nitric oxide |
Countries
Australia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nitrate-rich Beetroot Juice Beetroot juice containing naturally occurring nitrate (400mg total nitrate)
Beetroot juice: 70mls beetroot juice (400mg nitrate) given daily for 4 weeks | 30 |
| Nitrate-depleted Beetroot Juice Beetroot juice with nitrate removed
Nitrate-depleted beetroot juice: 70mls beetroot juice (nitrate-depleted) given daily for 4 weeks | 30 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
Baseline characteristics
| Characteristic | Nitrate-rich Beetroot Juice | Nitrate-depleted Beetroot Juice | Total |
|---|---|---|---|
| Age at diagnosis | 30.9 years STANDARD_DEVIATION 13.31 | 33.1 years STANDARD_DEVIATION 13.1 | 32 years STANDARD_DEVIATION 13.2 |
| Age, Continuous | 49.5 years STANDARD_DEVIATION 13.5 | 49.3 years STANDARD_DEVIATION 12.46 | 49.4 years STANDARD_DEVIATION 13 |
| Diagnosis confirmatory test (radiographic) | 30 Participants | 30 Participants | 60 Participants |
| Employment status, categorical (Part time, Full time)) Full time | 22 Participants | 26 Participants | 48 Participants |
| Employment status, categorical (Part time, Full time)) Part time | 7 Participants | 4 Participants | 11 Participants |
| Employment status, categorical (Part time, Full time)) Umemployed | 1 Participants | 0 Participants | 1 Participants |
| Factor precipitating diagnosis, categorical (family history screening; pain; hypertension;incidental Hypertension | 8 Participants | 2 Participants | 10 Participants |
| Factor precipitating diagnosis, categorical (family history screening; pain; hypertension;incidental Incidental | 2 Participants | 5 Participants | 7 Participants |
| Factor precipitating diagnosis, categorical (family history screening; pain; hypertension;incidental Other | 5 Participants | 4 Participants | 9 Participants |
| Factor precipitating diagnosis, categorical (family history screening; pain; hypertension;incidental Pain | 3 Participants | 6 Participants | 9 Participants |
| Factor precipitating diagnosis, categorical (family history screening; pain; hypertension;incidental Screening (family history) | 12 Participants | 13 Participants | 25 Participants |
| Family history of ADPKD No | 8 Participants | 4 Participants | 12 Participants |
| Family history of ADPKD Unknown | 0 Participants | 3 Participants | 3 Participants |
| Family history of ADPKD Yes | 22 Participants | 23 Participants | 45 Participants |
| Race/Ethnicity, Customized Asian | 8 Participants | 7 Participants | 15 Participants |
| Race/Ethnicity, Customized Caucasian | 20 Participants | 22 Participants | 42 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Female | 13 Participants | 14 Participants | 27 Participants |
| Sex: Female, Male Male | 17 Participants | 16 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 0 / 30 |
| other Total, other adverse events | 18 / 29 | 11 / 30 |
| serious Total, serious adverse events | 0 / 29 | 0 / 30 |
Outcome results
Primary
Change in Clinic Systolic and Diastolic Blood Pressure From Baseline to 4 Weeks (End of Study)
Change in systolic and diastolic blood pressure over two time points - from readings taken at baseline (visit 1) compared with readings taken at 4 weeks (which was the end of the study; visit 3)
Time frame: 4 weeks
Population: One patient in the nitrate-rich group was lost to follow-up.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nitrate-rich Beetroot Juice | Change in Clinic Systolic and Diastolic Blood Pressure From Baseline to 4 Weeks (End of Study) | Systolic blood pressure | -5.36 mmHg | Standard Deviation 12.69 |
| Nitrate-rich Beetroot Juice | Change in Clinic Systolic and Diastolic Blood Pressure From Baseline to 4 Weeks (End of Study) | Diastolic blood pressure | -3.55 mmHg | Standard Deviation 7.08 |
| Nitrate-depleted Beetroot Juice | Change in Clinic Systolic and Diastolic Blood Pressure From Baseline to 4 Weeks (End of Study) | Systolic blood pressure | -7.65 mmHg | Standard Deviation 14.07 |
| Nitrate-depleted Beetroot Juice | Change in Clinic Systolic and Diastolic Blood Pressure From Baseline to 4 Weeks (End of Study) | Diastolic blood pressure | -2.73 mmHg | Standard Deviation 7.81 |
Secondary
Average Change in Daily Home Systolic and Diastolic Blood Pressure Per Week, Over 4 Weeks
Reported change in blood pressure is average change per week, over 4 weeks
Time frame: 4 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Nitrate-rich Beetroot Juice | Average Change in Daily Home Systolic and Diastolic Blood Pressure Per Week, Over 4 Weeks | Systolic blood pressure | -0.51 mmHg/week |
| Nitrate-rich Beetroot Juice | Average Change in Daily Home Systolic and Diastolic Blood Pressure Per Week, Over 4 Weeks | Diastolic blood pressure | -0.24 mmHg/week |
| Nitrate-depleted Beetroot Juice | Average Change in Daily Home Systolic and Diastolic Blood Pressure Per Week, Over 4 Weeks | Systolic blood pressure | -0.55 mmHg/week |
| Nitrate-depleted Beetroot Juice | Average Change in Daily Home Systolic and Diastolic Blood Pressure Per Week, Over 4 Weeks | Diastolic blood pressure | -0.47 mmHg/week |
Secondary
Change in Salivary Nitric Oxide Metabolite Levels From Baseline to 4 Weeks (End of the Study)
Time frame: 4 weeks
Secondary
Change in Serum Nitric Oxide Metabolite Levels From Baseline to 4 Weeks (End of the Study)
Time frame: 4 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nitrate-rich Beetroot Juice | Change in Serum Nitric Oxide Metabolite Levels From Baseline to 4 Weeks (End of the Study) | 20.08 µM |
| Nitrate-depleted Beetroot Juice | Change in Serum Nitric Oxide Metabolite Levels From Baseline to 4 Weeks (End of the Study) | 0.97 µM |
Secondary
Serum Asymmetric Dimethylarginine at Baseline and at 4 Weeks (End of the Study)
Asymmetric dimethylarginine (ADMA) which is a recognized marker of endothelial dysfunction and inhibitor of nitric oxide
Time frame: 4 weeks
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Nitrate-rich Beetroot Juice | Serum Asymmetric Dimethylarginine at Baseline and at 4 Weeks (End of the Study) | Baseline ADMA level | 0.47 umol/L | Standard Deviation 0.08 |
| Nitrate-rich Beetroot Juice | Serum Asymmetric Dimethylarginine at Baseline and at 4 Weeks (End of the Study) | 4 week ADMA level (end of study) | 0.50 umol/L | Standard Deviation 0.1 |
| Nitrate-depleted Beetroot Juice | Serum Asymmetric Dimethylarginine at Baseline and at 4 Weeks (End of the Study) | Baseline ADMA level | 0.47 umol/L | Standard Deviation 0.09 |
| Nitrate-depleted Beetroot Juice | Serum Asymmetric Dimethylarginine at Baseline and at 4 Weeks (End of the Study) | 4 week ADMA level (end of study) | 0.52 umol/L | Standard Deviation 0.11 |
Secondary
Urinary Albumin to Creatinine Ratio at Baseline and at 4 Weeks (End of Study)
Time frame: 4 weeks
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Nitrate-rich Beetroot Juice | Urinary Albumin to Creatinine Ratio at Baseline and at 4 Weeks (End of Study) | Baseline | 2.2 mg/mmol |
| Nitrate-rich Beetroot Juice | Urinary Albumin to Creatinine Ratio at Baseline and at 4 Weeks (End of Study) | 4 weeks (end of study) | 2.5 mg/mmol |
| Nitrate-depleted Beetroot Juice | Urinary Albumin to Creatinine Ratio at Baseline and at 4 Weeks (End of Study) | Baseline | 3.9 mg/mmol |
| Nitrate-depleted Beetroot Juice | Urinary Albumin to Creatinine Ratio at Baseline and at 4 Weeks (End of Study) | 4 weeks (end of study) | 3.6 mg/mmol |