Calcitriol vs Vitamin D for Kidney Failure
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: University of Washington
Must be taking: Activated vitamin D
Must not be taking: Cholestyramine, Phenytoin, Ketoconazole
Disqualifiers: Parathyroidectomy, Calciphylaxis, Breast-feeding, others
No Placebo Group
Prior Safety Data
Approved in 3 Jurisdictions
Trial Summary
What is the purpose of this trial?The De-emphasize Parathyroid Hormone (DePTH) Study is a 12-month pragmatic, randomized, parallel-group, active comparator, open-label, blinded end-point study of 90 patients with incident or prevalent secondary hyperparathyroidism and kidney failure treated with in-center hemodialysis. It tests the hypothesis that low fixed-dose oral calcitriol (intervention) will have more favorable effects on a comprehensive panel of biomarkers that assesses mineral metabolism, bone turnover, and serum calcification propensity, compared with variably-dosed intravenous activated vitamin D titrated to PTH targets (usual care).
Do I have to stop taking my current medications for the trial?
The trial protocol does not specify if you need to stop taking your current medications, but you cannot participate if you are using cholestyramine, phenytoin/phenobarbital, or ketoconazole.
What data supports the effectiveness of the drug Calcitriol for kidney failure?
Research shows that intravenous calcitriol is more effective than oral calcitriol for managing renal bone disease, especially in patients with poor compliance and those prone to high calcium levels. Additionally, oral calcitriol is linked to a lower risk of death in patients with chronic kidney disease not on dialysis.
12345Is calcitriol safe for use in humans?
Calcitriol is generally well tolerated in humans, with studies showing it does not cause significant renal toxicity or severe side effects when used at recommended dosages. Hypercalcemia (high calcium levels in the blood) is infrequent and mild, usually manageable by adjusting calcium intake or dosage. Careful monitoring of calcium and kidney function is advised during treatment.
678910How does the drug calcitriol differ from other treatments for kidney failure?
Calcitriol is a form of active vitamin D that helps manage kidney failure by reducing parathyroid hormone levels, which can improve survival rates in patients with chronic kidney disease (CKD) not on dialysis. Unlike some other vitamin D treatments, calcitriol is associated with a higher risk of hypercalcemia (high calcium levels in the blood), but it offers a more direct approach to managing CKD-related complications.
35111213Eligibility Criteria
This trial is for patients with kidney failure on hemodialysis who have a condition called secondary hyperparathyroidism. Participants should not have other health issues that could interfere with the study.Inclusion Criteria
I am 18 years old or older.
My PTH levels are high, or I'm on IV vitamin D treatment.
I am receiving in-center hemodialysis for kidney failure.
Exclusion Criteria
Severe secondary hyperparathyroidism (PTH >=600 pg/mL x 2 consecutive measures at least 1 month apart despite paricalcitol >=10 mcg 3x/week or doxercalciferol >=5 mcg 3x/week or cinacalcet >30 mg/d)
I can give my own consent or have someone who can legally do it for me.
Calcium >9.8 mg/dL
+4 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive either a low fixed-dose of oral calcitriol or usual care with vitamin D doses titrated to PTH levels over 12 months
12 months
Monthly visits for blood work as part of routine dialysis care
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The DePTH Study compares two treatments: low fixed-dose oral calcitriol and variably-dosed IV activated vitamin D, to see which better affects mineral metabolism, bone turnover, and serum calcification in patients over 12 months.
2Treatment groups
Experimental Treatment
Active Control
Group I: Low dose oral calcitriolExperimental Treatment1 Intervention
Group II: Usual careActive Control1 Intervention
Oral calcitriol is already approved in United States, United States, European Union for the following indications:
๐บ๐ธ Approved in United States as Rocaltrol for:
- Hyperparathyroidism
- Hypocalcemia
- Psoriasis
๐บ๐ธ Approved in United States as Calcijex for:
- Hyperparathyroidism
- Hypocalcemia
๐ช๐บ Approved in European Union as Rocaltrol for:
- Hyperparathyroidism
- Hypocalcemia
- Psoriasis
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of WashingtonSeattle, WA
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Who Is Running the Clinical Trial?
University of WashingtonLead Sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)Collaborator
References
Calcitriol injection for the management of renal osteodystrophy. [2016]The introduction of synthetically produced calcitriol in the early 1970s was an important contribution to the prevention and treatment of renal bone disease. However, despite the efficacy and the availability of oral calcitriol many dialysis patients continued to develop secondary hyperparathyroidism (Norris, 1991). Effective treatment was often impossible in patients with osteitis fibrosa because even low oral doses of calcitriol could cause hypercalcemia (Andress, Norris, Coburn, Slatopolsky, & Sherrad, 1989). From 1981 to the present, numerous studies have been conducted that have demonstrated intravenous calcitriol as being more effective and having several advantages over the oral route of administration, particularly in patients with poor compliance and those with a tendency to develop hypercalcemia.
Long-term low-dose calcitriol treatment in predialysis chronic renal failure: can it prevent hyperparathyroid bone disease? [2013]In an uncontrolled open study 13 patients with moderate to preterminal renal failure were treated with low doses (average 0.36 micrograms/day) of calcitriol up to the time of renal transplantation, which was performed before dialysis had been initiated. A transiliac bone biopsy was obtained both at the start and at the end of the treatment period, the latter coinciding with renal transplantation. All patients who started calcitriol treatment at a creatinine clearance (Ccr) above 30 ml/min had normal bone histology at the time of transplantation, but this was not observed when calcitriol treatment was started at Ccr below 30 ml/min. The study suggests that full benefit of calcitriol at the bone level is obtained only if prophylactic administration is started early in the course of renal failure.
History of vitamin D treatment of renal osteodystrophy. [2018]Vitamin D treatment was tried when renal osteodystrophy was first recognized in the early 20th century, using vitamin D2, D3, or dihydrotachysterol. Large doses of vitamin D2 or D3 (150,000-500,000 IU) were prescribed by monitoring serum calcium, phosphate, and alkaline phosphatase. After the discovery of 1,25-dihydroxycholecalciferol, this compound or 1 alpha-hydroxycholecalciferol was applied to the treatment of renal osteodystrophy. In a preclinical study, especially of 1 alpha-hydroxycholecalciferol, nephritogenoside nephritis was the most responsive condition. These active vitamin D preparations are now widely used in patients with chronic renal failure under hemodialysis. Other active vitamin D compounds, such as hexafluoro-1,25-dihydroxycholecalciferol and 22-oxacalcitriol, are also under investigation.
Therapeutic use of calcitriol. [2021]The synthesis of 1ฮฑ,25-dihydroxyvitamin D3 (Calcitriol) takes place mostly in the kidneys through the action of 1ฮฑ-hydroxylase (CYP27B1) which converts 25(OH)D into 1,25(OH)2D3. Renal production of calcitriol is stimulated by PTH, low calcium and low phosphate and it is reduced by high phosphate and FGF23. Binding of 1ฮฑ,25-dihydroxyvitamin D3 to its receptor (VDR) causes gut absorption of calcium and phosphate, decrease in PTH synthesis, stimulation of FGF23. At the bone level calcitriol suppresses pre-osteoblasts and activates mature osteoblasts. VDR is present in a large variety of cells that do not have any direct role in the regulation of mineral metabolism. Calcitriol regulates immune and inflammatory response, cell turnover, cell differentiation, Renin production, reduces proteinuria and others. In patients with Chronic Kidney Disease (CKD) there is a decrease in calcitriol that is apparent at early stages of renal disease; this is probably due to the elevation of FGF23 which is present since very early stage of CKD. In CKD stage, 3-4 moderate doses of calcitriol are effective to control secondary hyperparathyroidism and observational studies suggest that calcitriol therapy increases survival and slows the progression of renal disease as long as phosphate and calcium levels are controlled. Calcitriol (0.5 ยตg calcitriol twice per week) has been effective in decreasing proteinuria in patients with IgA nephropathy. In dialysis patients, the administration of calcitriol reduces serum PTH levels but it is also known that high doses of calcitriol are associated with hypercalcemia and worse control of hyperphosphatemia. In kidney transplant patients, the administration of calcitriol, 0.5 ยตg/48h prevents bone mass loss during the first few months after transplantation.
Association of oral calcitriol with improved survival in nondialyzed CKD. [2022]Parenteral vitamin D is associated with improved survival among long-term hemodialysis patients. Among nondialyzed patients with chronic kidney disease (CKD), oral activated vitamin D reduces parathyroid hormone levels, but the impact on clinical outcomes is unknown. We evaluated associations of oral calcitriol use with mortality and dialysis dependence in 1418 nondialysis patients with CKD and hyperparathyroidism in the Veterans' Affairs Consumer Health Information and Performance Sets database. Incident calcitriol users and nonusers were selected on the basis of stages 3 to 4 CKD, hyperparathyroidism, and the absence of hypercalcemia before calcitriol use and then were matched by age and estimated kidney function. During a median follow-up of 1.9 yr, 408 (29%) patients died and 217 (16%) initiated long-term dialysis. After adjustment for demographics; comorbidities; estimated kidney function; medications; and baseline levels of parathyroid hormone, calcium, and phosphorous, oral calcitriol use was associated with a 26% lower risk for death (95% confidence interval 5 to 42% lower; P = 0.016) and a 20% lower risk for death or dialysis (95% confidence interval 1 to 35% lower; P = 0.038). The association of calcitriol with improved survival was not statistically different across baseline parathyroid hormone levels. Calcitriol use was associated with a greater risk for hypercalcemia. In conclusion, oral calcitriol use is associated with lower mortality in nondialysis patients with CKD.
Vitamin D replacement therapy and renal function. Calcitriol v dihydrotachysterol. [2019]We treated 24 patients who had chronic renal insufficiency and renal osteodystrophy with either calcitriol (1,25-dihydroxyvitamin D3) or dihydrotachysterol. Renal function was evaluated before and during treatment to determine if these vitamin D analogues caused an accelerated rate of renal function deterioration. An accelerated rate of increase in the serum creatinine level was found in three of 12 patients in each treatment group after therapy was started, but the mean rate of increase during treatment did not differ significantly from the rate during the pretreatment control period in either group. The occurrence of hypercalcemia or an excessive serum calcium x phosphorus-product did not correlate with the rate of change in renal function during treatment with either drug. We concluded that children receiving calcitriol are not at greater risk for an accelerated rate of renal function deterioration than are children treated with dihydrotachysterol. Furthermore, neither vitamin D analogue could be directly implicated as a cause of an accelerated rate of renal function deterioration when episodes of hypercalcemia were transient and occurred infrequently.
[Comparative evaluation of the effectiveness of vitamin D3 preparations (1-alpha-hydroxy- and 1-alpha,25-dihydroxycholecalciferol in various forms of osteoporosis and osteomalacia]. [2016]Clinical investigations have shown that 1 alpha-hydroxycholecalciferol (oxydevit, alphacalcidiol) and 1 alpha, 25-dihydroxycholecalciferol (rocaltrol) are act vitamin D3 agents producing a positive clinical effect in different types of osteoporosis and osteomalacia. Clinical improvement of the patients' status (alleviation of the pain syndrome, an increase in motor activity) was noted in 1-2 mos., an x-ray picture of regeneration of the bone structure of both axial and peripheral skeleton--in 6-12 mos. after the initiation of therapy. Therapy was attended by an increase in the serum content of total and ionized calcium, the return of alkaline phosphatase activity to normal, and a decrease in the level of parathormone. During prolonged therapy these agents administered at daily doses of 0.25-2 micrograms caused no pathological side-effects and hypercalcemia. In osteoporotic conditions all these drugs were equal in their clinical effectiveness. Rocaltrol has some advantages in the presence of associated liver pathology.
Calcitriol. A review of its use in the treatment of postmenopausal osteoporosis and its potential in corticosteroid-induced osteoporosis. [2018]A synthetic form of calcitriol (1,25-dihydroxycholecalciferol; 1,25-dihydroxyvitamin D3), the most physiologically active metabolite of vitamin D, has shown efficacy in the treatment of postmenopausal osteoporosis and promise in corticosteroid-induced osteoporosis. Although results of small studies investigating calcitriol in the treatment of postmenopausal osteoporosis have been conflicting, a clinical trial in 622 women with postmenopausal osteoporosis demonstrated that patients with mild to moderate disease who received calcitriol (0.25 microgram twice daily) had a significant 3-fold lower rate of new vertebral fractures after 3 years of treatment, compared with patients receiving elemental calcium 1000 mg/day. In patients commencing long term treatment with prednisone or prednisolone, calcitriol 0.5 to 1.0 micrograms/day plus calcium 1000 mg/day, administered with or without intranasal calcitonin 400 IU/day, prevented steroid-induced bone loss. Overall, calcitriol is well tolerated. As shown in clinical studies, at recommended dosages hypercalcaemia is infrequent and mild, generally responding to reductions in calcium intake and/or calcitriol dosage. The narrow 'therapeutic window' of calcitriol requires that its use be adequately supervised, with periodic monitoring of serum calcium and creatinine levels. However, significant renal toxicity has not been seen in patients with osteoporosis treated with calcitriol in high dosages for several years in comparative and noncomparative trials. In conclusion, as with other drugs currently used in the management of patients with osteoporosis, questions remain to be answered regarding the efficacy of calcitriol relative to other agents, and its tolerability in such patients during the very long term. Nonetheless, at this stage, calcitriol should be considered a useful treatment option in patients with mild to moderate postmenopausal osteoporosis.
Action of 1,25-dihydroxyvitamin D3 on calcium balance and bone turnover and its effect on vertebral fracture rate. [2019]In postmenopausal osteoporotics, malabsorption of calcium is associated with reduced levels of serum 1,25-dihydroxyvitamin D. Metabolic studies have shown that calcium absorption can be normalized and calcium balance improved after administration of oral doses of synthetic 1,25-dihydroxyvitamin D3 (Rocaltrol) 0.25 micrograms twice daily. Further studies performed at two centers compared the effect of Rocaltrol 0.25 micrograms twice daily versus placebo on vertebral fracture rates in osteoporotics. A significant reduction in vertebral fracture rates was seen at the end of 1 year. Those patients who continued on Rocaltrol for a second and third year showed a progressive decrease in vertebral fractures. Rocaltrol, administered at a dose of 0.25 micrograms twice daily, seldom causes hypercalcuria or hypercalcemia in osteoporotic patients on a typical calcium intake of 700 to 800 mg/d. Careful measurements of renal function over a period of 3 years in patients treated with Rocaltrol, 0.25 micrograms twice daily, showed no deterioration in renal function. These data suggest that 1,25-dihydroxyvitamin D3 is a useful therapy in the management of patients with postmenopausal osteoporosis, particularly those who have malabsorption of calcium. We found that it improves calcium balance, reduces the vertebral fracture rate, and is safe to use provided that the dietary calcium is monitored and does not exceed 800 mg/d.
[Use of vitamin D 2 and its metabolites in chronic glomerulonephritis in children]. [2016]Comparative assessment of the action of vitamin D2 in high doses, of oxydevit and rocaltrol applied in renal osteopathies has demonstrated that they are equally effective in elevating the calcium concentration in blood serum occurring at the expense of its increased absorption by the intestine. At the same time certain differences have been discovered in the action of these agents on endocrine regulation. The data obtained provide evidence in favour of the use of vitamin D2 in high doses or of its metabolites not only in renal osteopathies at the stage of chronic renal failure but also in the management of the disorders of phosphorus-calcium metabolism in patients with the nephrotic syndrome in the functional-compensation stage after continuous use of corticosteroids, heparin and diuretics.
Hypercalcemia-induced renal insufficiency during therapy with dihydrotachysterol. [2016]During vitamin-D therapy drug accumulation and intoxication should be considered. In the present study we report on five patients with renal insufficiency during therapy with dihydrotachysterol or calcitriol. Four patients received dihydrotachysterol for 29 (7-44) years and one patient received calcitriol for 4 years to treat hypoparathyroidism after thyroid surgery. As confirmed by renal biopsy impairment of renal function was due to calcifications as a consequence of prolonged hypercalcemia. The effective duration of dihydrotachysterol is ten days as compared with five days for calcitriol. Severe hypercalcemic episodes with dihydrotachysterol are longer-lasting than those with the shorter acting vitamin-D derivatives. Further, they occur with higher incidence as was shown by our own observations and previously published data by other workers. Hence, impairment of renal function during therapy with dihydrotachysterol should be considered as being due to hypercalcemia and hypercalciuria.
Management of secondary hyperparathyroidism: the gap between diagnosis and treatment. The Renal Osteodystrophy Multicenter Enquiry. [2019]In mild secondary hyperparathyroidism, small daily doses of oral calcitriol represent the physiological form of replacement of this hormone, but in moderate or severe cases, higher doses of calcitriol are needed to suppress parathyroid gland overactivity. Unfortunately, in chronic renal failure, these 2 different forms of calcitriol prescription are not always adequately selected. This review will focus on the current use of calcitriol in renal failure. It includes data from a recent multicenter trial carried out in Spain in which data was gathered from dialysis patients. This trial was designed to determine the current approach to the prevention, diagnosis, and treatment of renal osteodystrophy, with a special emphasis on the gap found between diagnosis and treatment of secondary hyperparathyroidism. Our main goal should be to achieve an adequate and early management of secondary hyperparathyroidism to decrease the number of patients suffering from irreversible enlargement of the parathyroid glands.
[Role of paracalcitol in the management of non-dialysis CKD: state of art and... Unmet needs]. [2014]Chronic kidney disease (CKD) is associated with a high risk of cardiovascular morbidity and mortality due to the high prevalence of traditional risk factors and the presence of factors specific to CKD. Vitamin D deficiency and secondary hyperparathyroidism are the earliest complications in CKD, and observational data show that low plasma vitamin D is an independent predictor of death in patients with CKD. Oral supplementation with active oral vitamin D appears to be associated with greater survival but a significant improvement in renal outcome has not been demonstrated, probably because of its unwanted side effects (increase in plasma calcium and phosphate levels). Oral paracalcitol, a new vitamin D receptor activator, is now available for CKD patients not yet on dialysis. It suppresses PTH with a low incidence of increased serum calcium and phosphate levels in patients treated with dialysis and when high doses are administered. Furthermore, recent data show that paracalcitol treatment in CKD patients also results in a significant reduction of albuminuria, which is a major risk factor for cardiorenal outcome. The antiproteinuric effect of paracalcitol appears to be the result of intrarenal suppression of the renin-angiotensin system (RAS). Therefore, paracalcitol may be mostly effective in reducing albuminuria in patients already treated with RAS inhibitors who show compensatory increments of RAS components. Studies in large patients series and with adequate follow-up are needed to evaluate the effects of long-term paracalcitol treatment in CKD and its potential role in improving renal outcome in comparison not only with placebo but also other vitamin D metabolites and analogues.