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| [ Print-friendly version ] |
| A study to test whether spironolactone and dietary nitrate (as beetroot juice) alter blood vessel stiffness in Type 2 Diabetes |
| ISRCTN | ISRCTN25003627 |
| DOI | 10.1186/ISRCTN25003627 |
| ClinicalTrials.gov identifier | |
| EudraCT number | |
| Public title | A study to test whether spironolactone and dietary nitrate (as beetroot juice) alter blood vessel stiffness in Type 2 Diabetes |
| Scientific title | A study to test whether spironolactone and dietary nitrate (as beetroot juice) (I) compared to controls, alter blood vessel function, measured as the Cardiac-ankle vascular index (O) or as arterial pulse wave velocity (O) in Type 2 Diabetes (P): a randomised trial |
| Acronym | Vasera Study |
| Serial number at source | 13648 |
| Study hypothesis |
Blood vessel damage in diabetes is a major threat to the health of anyone so diagnosed. There is strong evidence that people with diabetes develop stiffening of their arteries due to excess collagen formation in the blood vessel walls.
Spironolactone is an antagonist of the major hormone (aldosterone) that may induce this collagen excess. Similarly there is quite good evidence that dietary Nitrate (as beetroot juice) may help protect the blood vessels. The aim of the trial is to find out whether spironolactone and dietary Nitrate can improve vascular function in a population of Type 2 diabetes patients and subjects at risk of diabetes. The physiological measures of vascular function are the Cardiac-ankle vascular Index (CAVI), Pulse Wave Analysis (PWA), Pulse Wave Velocity (PWV) and central blood pressure (BP), all measured from a BP cuff device or a tonometer. We will also be looking at capillary density measures in the fingers, 24h readings of vascular function, kidney filtrations of Sodium and Potassium and other cardiovascular related markers. More details can be found at: http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=13648 |
| Lay summary |
Background and study aims
Blood vessel damage in diabetes, and probably in people who are overweight, is a major threat to the health of anyone with the condition. There is strong evidence that people with diabetes develop stiffening of their arteries due to excess scar formation in blood vessel walls. We want to test whether a treatment usually given for high blood pressure and a vegetable juice can help prevent the scarring and improve blood vessel function. Who can participate? Men and women aged 18 to 80 years with diagnosed Type 2 diabetes, or at risk of diabetes, for example by being overweight and found to have raised blood sugar. You will not be able to take part in this study if you fall within any of the following categories: -If you have an ongoing (chronic) illness of any type that may interfere with your ability to participate. -If your kidney function, measured at the screening visit, is impaired. -If major complications are restricting your mobility. -If you are pregnant or breastfeeding What does the study involve? If you decide to take part and are suitable for the study we will ask you to come to the Clinical Research Facilities (St Thomas’ Hospital or King’s College Hospital) for a screening visit where we will measure your blood pressure (BP), height, weight and ask you questions about your medical history, we will then take a blood sample and a urine sample. If you are eligible, we will then use non-invasive and painless devices to measure the health of your blood vessels. The devices generally use a simple cuff (as used for blood pressure). During these, we will ask you to keep still for a few minutes while we fit and inflate cuffs around your ankles and arms. There is also a small cuff on one side of the neck which is not inflated above 60mmHg (less tight than a man’s tie). They have all been found to be entirely safe. We will also measure the number of small vessels in your finger with a simple, painless microscope, which takes about 5 minutes. An Electrocardiogram (ECG) and an Echocardiogram to assess how well the heart pumps will be offered to you at the start and end of the study. These measures will be repeated up to 5 times in the study, after 2 weeks, then every 3 months from the start of the treatment for 1 year. Visits will be required after 2 weeks after starting treatment and at month 2 where we will only take a blood sample and measure your BP. If you are willing we will also ask you to collect your urine for 24h 3 to 4 times during the study and ask you to wear a cuff on your arm measuring your BP for 24h, which also measures blood vessel stiffness. At your second visit we will provide you with the treatment to take during the study. This will be pills, either as spironolactone or doxazosin – which both lower BP and a beetroot juice or a control juice (beetroot juice but without Nitrate). You take these pills and juice daily with your current treatment. These treatments are allocated by ‘randomization’, that is purely by chance as generated by computer. Neither you nor we decide which treatment you will receive; also neither you nor we will know which you are taking until the study ends, so that it will not affect the results. What are the possible benefits and risks of participating? You will have regular vascular and blood pressure check up that goes beyond your routine care. We will check your kidney function often and we will contact you if there are any problems. At the end of the study you will receive the results of all your tests. We will reimburse you travel expenses for a maximum of £15 per visit and some refreshment will be provided at the end of each visit. Taking blood samples may cause minor discomfort with a small chance of minor bruising. Many measures of BP can make the arm feel a bit squeezed and leave a few marks which go soon after. Vascular measures are very similar to BP. Most people have no problems with either type of pill but as always, some people have ‘side-effects’. These are not common but see list below here. For spironolactone, the blood potassium increases a little (harmless unless it goes very high, usually when kidney function is impaired, which is why we measure it at the start and through the study). Other rarer problems can include a skin rash and in men some tenderness in the nipples (very rare in women). Occasionally, problems with erectile function can occur in men but ’viagra-like’ treatment helps (this can be provided free by your GP). Doxazosin has few problems but dizziness can occur. Where is the study run from? St Thomas’ Hospital or King’s College Hospital in London When is the study starting and how long is it expected to run for? The recruitment will run from February 2013 for 2 years. Who is funding the study? The study is funded by FUKUDA Denshi Japan. Who is the main contact? Virginia Govoni vaserastudy@kcl.ac.uk |
| Ethics approval | NRES Committee- London Central, 21st December 2012, ref: 12/LO/1850 |
| Study design | Randomised; Interventional; Design type: Treatment |
| Countries of recruitment | United Kingdom |
| Disease/condition/study domain | Topic: Diabetes Research Network; Subtopic: Type 2; Disease: Cardiovascular disease, Hypertension, Diabetic Control, Nutrition, Pre Diabetes |
| Participants - inclusion criteria |
1. Anyone (male or female, age 18-80) with ‘diagnosed’ type 2 Diabetes or at risk of type 2 Diabetes (being overweight BMI >= 27 kg/m2) or found to have impaired glucose tolerance by fasting glycaemia or by glucose tolerance testing will be eligible. Please see under exclusion criteria for limits to this.
2. Participants need to be able to understand the protocol and be willing to comply with it |
| Participants - exclusion criteria |
1. Ongoing (chronic) illness of any type interfering with patient ability to participate
2. Major complications restricting mobility including active foot ulceration or amputation may be exclusion criteria, but only if the patient feels they cannot manage 3. Previous adverse reactions to Spironolactone or Doxazosin. (If patients are already on either of these, we can discuss alternatives) 4. Renal function by eGFR < 45 mls per minute (approximately - i.e. if one test is around 43 and another is around 46 the average of around 45 is acceptable) 5. Objective renal function tests for creatinine > 180 umol/l (when eGFR will be < 45 mls/ min). 6. All other aspects of diabetic control will be acceptable except gross disturbances of glycaemia with HbA1c > 11% and fasting random glucose > 12mmol/l. Those will not be indications to withdraw patients, but only as exclusions for entry (& once improved can become eligible). 7. For women: being pregnant or breastfeeding for the duration of the study |
| Anticipated start date | 01/02/2013 |
| Anticipated end date | 02/06/2014 |
| Status of trial | Ongoing |
| Patient information material | Not available in web format, please use the contact details below to request a patient information sheet |
| Target number of participants | UK Sample Size: 120 |
| Interventions |
Drugs: Spironolactone at 12.5 mg titrated up to 25 mg or 50mg daily for 6months, or up to 1 year if subject are willing.
Doxazosin at 4mg, titrated up to 8mg and 16mg for the same period. Nutritional, 70ml high Nitrate beetroot juice (nitrate content: 4,5mmols) from James WHite Drinks, 1 a day for 3 months, then a 70 ml juice with a nitrate content of 7.5mmols for another 3 months,up to 1 year if willing Control: 70ml control beetroot juice from James WHite Drinks, 1 a day for 6 months, up to 1 year if willing Follow Up Length: 12 month(s) |
| Primary outcome measure(s) | Change in vascular function measured as CAVI (Cardio-Ankle Vascular index); Timepoint(s): baseline visit, 2 weeks, 2,3,6,12 months |
| Secondary outcome measure(s) |
1. Change in capillary density; Timepoint(s): baseline, 3 and 6 months
2. Change in hormones related to diabetes and hypertension; Timepoint(s): baseline, 2 weeks, 2,3,6,12 months 3. Change in PWV (Pulse Wave velocity) in relation to changes in BP (Blood Pressure); Timepoint(s): Baseline, 2 weeks, 2,3,6,12 months 4. Changes in urinary Sodium, Potassium; Timepoint(s): baseline, 2 weeks, 2,3, 6,12 months |
| Sources of funding | Fukuda Denshi UK Ltd (UK) |
| Trial website | |
| Publications | |
| Contact name | Mrs Virginia Govoni |
| Address |
3.07 Franklin-Wilkins Building
150 Stamford Street |
| City/town | London |
| Zip/Postcode | SE1 9NH |
| Country | United Kingdom |
| vaserastudy@kcl.ac.uk | |
| Sponsor | King's College London (UK) |
| Address |
Medicine
Franklin-Wilkins building 150 Stamford street |
| City/town | London |
| Zip/Postcode | SE1 9NH |
| Country | United Kingdom |
| Sponsor website: | http://www.kcl.ac.uk/ |
| Date applied | 31/01/2013 |
| Last edited | 19/02/2013 |
| Date ISRCTN assigned | 31/01/2013 |
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