Diabetic kidney disease. MedDRA version: 17.0 Level: LLT Classification code 10009119 Term: Chronic renal failure System Organ Class: 100000004857 MedDRA version: 17.0 Level: PT Classification code 10067585 Term: Type 2 diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Interventions
Trade Name: Rocaltrol
Pharmaceutical Form: Capsule
INN or Proposed INN: CALCITRIOL
CAS Number: 32222-06-3
Concentration unit: µg microgr
Sponsors
King's College London
Guy's and St.Thomas' NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients with a diagnosis of T2DM. 2. Patients aged between 40 and 75 years (inclusive). 3. Chronic Kidney disease (CKD) stage 3 [estimated glomerular filtration rate (eGFR*) 30-59 ml/min on the two most recent (within 12 months) consecutive measurements]. 4. A history of an elevated urinary albumin excretion rate (UAER) [albumin: creatinine ratio= 2.5 mg/mmol in men and =3mg/mmol in women on more than three occasions or UAER =20mcg/min on at least two timed urine collections or two or more positive urine dipsticks results for proteinuria or two or more urine protein creatinine ratios (PCR)>15 mg/mmol] or clinical evidence of diabetic nephropathy 5. Normal corrected serum calcium (2.1-2.6mmol/l). 6. Normal phosphate (0.8-1.5 mmol/l) levels. 7. A raised intact parathyroid hormone (iPTH) level between 30 pg/ml and 200pg/ml at screening visit or a history of a raised intact parathyroid hormone (iPTH) level between 30 pg/ml and 200pg/ml in the 3 months preceding screening visit. 8. Written informed consent to participate in the study prior to any study procedures. 9. Ability to communicate and comply with all study requirements. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 150 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 150
Exclusion criteria
Exclusion criteria: • An iPTH =200 pg/ml at study entry (a conservative treatment threshold for initiating active vitamin D treatment for prevention of renal osteodystrophy). • History of non diabetic or obstructive kidney disease. • Poorly controlled hypertension (systolic and diastolic blood pressure >180mmHg and >110 mmHg respectively). • Presence of connective tissue diseases known to affect arterial vasculature. • Atrial fibrillation or other cardiac rhythm disorders. • Pregnancy or lactation. • History of a cardiovascular or cerebrovascular event in the preceding 6 months. • Patients already on vitamin D (inactive or active) treatment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main research question is to evaluate the effect of Calcitriol treatment as compared to placebo on arterial stiffness in patients with type 2 diabetes and chronic kidney disease. Arterial stiffness is a marker and predictor of cardiovascular disease risk. Arterial stiffness will be assessed by aortic pulse wave velocity (Ao-PWV) which is a measure of arterial stiffness. Ao-PWV measures the the speed of transmission of the pulse wave along the aorta the largest blood vessel in the body. The greater the speed the greater the arterial stiffness. Interventions that recuce arterial stiffness may prevent cardiovascular disease. Currently it is not known if treatment with Calcitriol can affect arterial stiffness in patients with diabetes and kidney disease. We wish to study the effect of Calcitriol or placebo as add on treatment to existing medical treatments on arterial stiffness in a placebo controlled double blind study. Patients will continue with other medical treatments for their ;Secondary Objective: Secondary research questions will be to evaluate the effect of Calcitriol treatment as compared to placebo on the amount of the protein albumin in the urine which is a marker of kidney disease and heart disease. Other secondary questions will be to compare the effect of calcitriol and placebo on augmentation index (a measurement of the pulse wave reflection on central pressures) measured at the wrist over the radial artery with a small pencil like probe. Similar to the Aortic pulse wave velocity measurements this is also non invasive. Other secondary endpoints questions include blood pressure, kidney function as measured by estimated glomerular filtration rate, changes in calcium and phosphate levels in the blood and hormones involved in regulating bone metabolism and blood pressure and quality of life as measured by a questionnaire. ; Primary end point(s): The primary end point will be change from basel | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints will be change from baseline in; UAER, augmentation index, brachial and central systolic and diastolic blood pressure, progression to clinical indication for vitamin D replacement or iPTH=200 pg/ml, eGFR, serum calcium and phosphate levels, alkaline phosphate levels, urine calcium excretion, quality of life, number of hypercalcaemic events requiring withdrawal from study, hsCRP, iPTH, plasma renin activity and active vitamin D levels.Flow mediated dilatation, cardiac autonomic tests are exploratory secondary endpoints and will also be reported along with the above endpoints in final clinical study report (CSR);Timepoint(s) of evaluation of this end point: All trial visits | — |
Countries
United Kingdom
Contacts
Public ContactDiabetes Research
King's College London
Outcome results
None listed