Calcitriol vs Vitamin D for Kidney Failure

Overseen By Simon Hsu, MD, MS

Age: 18+

Sex: Any

Trial Phase: Phase 2

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 All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a low-dose oral form of calcitriol, a type of vitamin D, manages certain aspects of kidney disease better than the usual intravenous activated vitamin D treatment. It targets individuals with kidney failure undergoing regular dialysis who have secondary hyperparathyroidism, a condition characterized by an overactive parathyroid gland. Participants must have kidney failure, be on dialysis, and have a history of high parathyroid hormone levels. The study aims to determine which treatment better supports bone and mineral health. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that taking calcitriol orally is generally safe, but regular check-ups remain important. The most common side effect is hypercalcemia, or elevated calcium levels in the blood. Some people might experience this, so doctors monitor calcium levels to manage it. Overall, calcitriol has been used in patients with kidney issues, and while it requires careful monitoring, past studies have found it to be well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for kidney failure focus on managing symptoms and complications, often using vitamin D supplements to help maintain bone health. But calcitriol, a form of active vitamin D, works differently by directly regulating calcium and phosphate balance in the body. Researchers are excited about calcitriol because it offers a more targeted approach, potentially reducing complications like bone disease more effectively than standard vitamin D. This could lead to better overall outcomes for patients with kidney failure.

What evidence suggests that this trial's treatments could be effective for secondary hyperparathyroidism and kidney failure?

This trial will compare low-dose oral calcitriol with usual care for managing secondary hyperparathyroidism in people with kidney failure. Research has shown that oral calcitriol can help manage this condition, which affects bone health. Studies have found that calcitriol, a type of vitamin D, can lower parathyroid hormone (PTH) levels, which is important for maintaining healthy bones. However, it can also raise calcium levels in the blood excessively, leading to hypercalcemia. Because calcitriol remains in the body longer in individuals with kidney problems, it might be more effective for them. Observational studies suggest that vitamin D can provide overall health benefits for those with chronic kidney disease. ^{1 2 3 4 5}

Who Is on the Research Team?

Simon Hsu, MD, MS

Principal Investigator

University of Washington

Are You a Good Fit for This Trial?

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

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• IV activated vitamin D
• Oral calcitriol

Trial Overview 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.

How Is the Trial Designed?

Group I: Low dose oral calcitriol Experimental Treatment 1 Intervention

Group II: Usual care Active Control 1 Intervention

Oral calcitriol is already approved in United States, European Union for the following indications:

Approved in United States as Rocaltrol for:

• Hyperparathyroidism
• Hypocalcemia
• Psoriasis

Approved in United States as Calcijex for:

• Hyperparathyroidism
• Hypocalcemia

Approved in European Union as Rocaltrol for:

• Hyperparathyroidism
• Hypocalcemia
• Psoriasis

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

In a clinical trial involving 622 women with postmenopausal osteoporosis, calcitriol significantly reduced the rate of new vertebral fractures by three times compared to those receiving only calcium after three years of treatment.

Calcitriol is generally well tolerated with infrequent mild hypercalcemia, but its use requires careful monitoring due to its narrow therapeutic window, making it a viable option for treating mild to moderate postmenopausal osteoporosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Calcitriol. A review of its use in the treatment of postmenopausal osteoporosis and its potential in corticosteroid-induced osteoporosis. Dechant, KL., Goa, KL.[2018]

High doses of vitamin D2, oxydevit, and rocaltrol are equally effective in increasing blood calcium levels by enhancing intestinal absorption, making them viable treatments for renal osteopathies.

The study suggests that vitamin D2 and its metabolites can be beneficial not only for chronic renal failure but also for managing phosphorus-calcium metabolism disorders in patients with nephrotic syndrome, especially those on long-term corticosteroids, heparin, and diuretics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Use of vitamin D 2 and its metabolites in chronic glomerulonephritis in children]. Naumova, VI., Rusnak, FI., Vereskova, SA., et al.[2016]

Intravenous calcitriol has been shown to be more effective than oral calcitriol in treating renal bone disease, especially in dialysis patients who often struggle with compliance and risk of hypercalcemia.

Despite the availability of oral calcitriol since the 1970s, many patients continued to experience secondary hyperparathyroidism, highlighting the need for alternative treatment methods like intravenous administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Calcitriol injection for the management of renal osteodystrophy. Peacock, E.[2016]

Vitamin D treatments, particularly 1,25-dihydroxycholecalciferol and 1 alpha-hydroxycholecalciferol, have been effectively used to manage renal osteodystrophy in patients with chronic renal failure undergoing hemodialysis.

Preclinical studies indicate that 1 alpha-hydroxycholecalciferol is particularly effective in treating nephritogenoside nephritis, highlighting its potential as a targeted therapy in renal conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

History of vitamin D treatment of renal osteodystrophy. Morii, H., Ishimura, E., Inoue, T., et al.[2018]

In a study of 1418 nondialysis patients with chronic kidney disease (CKD), oral calcitriol was linked to a 26% lower risk of death and a 20% lower risk of death or needing dialysis over a median follow-up of 1.9 years.

While calcitriol use improved survival rates, it also increased the risk of hypercalcemia, highlighting the need for careful monitoring in patients with CKD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of oral calcitriol with improved survival in nondialyzed CKD. Shoben, AB., Rudser, KD., de Boer, IH., et al.[2022]

In a study involving 13 patients with moderate to preterminal renal failure, low doses of calcitriol were administered before renal transplantation, showing that early treatment can lead to normal bone histology in patients with better kidney function (Ccr above 30 ml/min).

The results indicate that starting calcitriol treatment early in the course of renal failure is crucial for achieving optimal bone health, as patients who began treatment with lower kidney function did not show the same benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term low-dose calcitriol treatment in predialysis chronic renal failure: can it prevent hyperparathyroid bone disease? Nordal, KP., Dahl, E., Halse, J., et al.[2013]

In a study of five patients with renal insufficiency, prolonged use of dihydrotachysterol (up to 44 years) and calcitriol (4 years) led to renal impairment due to calcifications from prolonged hypercalcemia.

Dihydrotachysterol has a longer effective duration and is associated with more severe and longer-lasting hypercalcemic episodes compared to calcitriol, indicating a higher risk of renal function impairment during its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypercalcemia-induced renal insufficiency during therapy with dihydrotachysterol. Jehle, DR., Keller, F., Schwarz, A., et al.[2016]

In a study of 24 patients with chronic renal insufficiency and renal osteodystrophy, neither calcitriol nor dihydrotachysterol was found to significantly accelerate the deterioration of renal function during treatment.

Episodes of hypercalcemia were infrequent and did not correlate with changes in renal function, indicating that both vitamin D analogues are safe options for managing renal osteodystrophy without increasing the risk of renal decline.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin D replacement therapy and renal function. Calcitriol v dihydrotachysterol. Hymes, LC., Warshaw, BL.[2019]

1 alpha-hydroxycholecalciferol and 1 alpha, 25-dihydroxycholecalciferol are effective vitamin D3 agents that improve clinical symptoms of osteoporosis and osteomalacia within 1-2 months, with bone regeneration observable in 6-12 months.

Both treatments are safe, showing no significant side effects or hypercalcemia at daily doses of 0.25-2 micrograms, and are equally effective in osteoporotic conditions, although Rocaltrol may be preferred for patients with liver issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Comparative evaluation of the effectiveness of vitamin D3 preparations (1-alpha-hydroxy- and 1-alpha,25-dihydroxycholecalciferol in various forms of osteoporosis and osteomalacia]. Zarubina, NA., Rozhinskaia, LIa., Bukhman, AI., et al.[2016]

Calcitriol, the active form of vitamin D, is crucial for regulating calcium and phosphate levels in the body, and its production decreases in patients with Chronic Kidney Disease (CKD), which can lead to complications like secondary hyperparathyroidism.

Moderate doses of calcitriol (0.5 µg twice per week) have been shown to effectively manage secondary hyperparathyroidism and reduce proteinuria in CKD patients, while also preventing bone mass loss in kidney transplant patients, highlighting its therapeutic potential when phosphate and calcium levels are monitored.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic use of calcitriol. Rodriguez, M., Munoz-Castaneda, JR., Almaden, Y.[2021]

In patients with mild secondary hyperparathyroidism, small daily doses of oral calcitriol can effectively replace the hormone, but higher doses are necessary for moderate to severe cases to control parathyroid gland activity.

A recent multicenter trial in Spain highlighted the need for better selection of calcitriol dosages in chronic renal failure patients to prevent complications like irreversible enlargement of the parathyroid glands, emphasizing the importance of early and adequate management of secondary hyperparathyroidism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of secondary hyperparathyroidism: the gap between diagnosis and treatment. The Renal Osteodystrophy Multicenter Enquiry. Díaz-Corte, C., Cannata-Andía, JB.[2019]

Oral paracalcitol, a new vitamin D receptor activator, effectively suppresses parathyroid hormone (PTH) levels in chronic kidney disease (CKD) patients with a low risk of increasing serum calcium and phosphate, making it a safer option compared to traditional vitamin D supplements.

Paracalcitol treatment has been shown to significantly reduce albuminuria, a key risk factor for cardiovascular and renal complications, likely by suppressing the renin-angiotensin system, especially in patients already on RAS inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Role of paracalcitol in the management of non-dialysis CKD: state of art and... Unmet needs]. Mascia, S., Garofalo, C., Donnarumma, G., et al.[2014]

In postmenopausal women with osteoporosis, taking 0.25 micrograms of synthetic 1,25-dihydroxyvitamin D3 (Rocaltrol) twice daily significantly reduced vertebral fracture rates over one year, with continued use leading to further reductions in fractures.

Rocaltrol is safe for long-term use, as it rarely causes high calcium levels in the blood or urine and does not impair kidney function, making it a beneficial treatment for those with calcium malabsorption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Action of 1,25-dihydroxyvitamin D3 on calcium balance and bone turnover and its effect on vertebral fracture rate. Gallagher, JC., Riggs, BL.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3280034/

Vitamin D Therapy in Chronic Kidney Disease and End ... This review outlines the available evidence for multiple outcomes associated with vitamin D in patients with kidney disease.

2. sciencedirect.com sciencedirect.com/science/article/pii/S0002916523026680

Efficacy and safety of a short course of very-high-dose ... Conclusion: Short-term, high-dose oral cholecalciferol treatment of vitamin D deficiency in hemodialysis patients appears to be effective and with no evidence ...

3. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK526025/

Calcitriol - StatPearls - NCBI Bookshelf - NIH The elimination half-life of calcitriol is significantly prolonged in patients with chronic kidney disease and hemodialysis.

4. academic.oup.com academic.oup.com/ckj/article/17/8/sfae227/7716710

Vitamin D therapy in chronic kidney disease - Oxford Academic A 2023 systematic review found moderate quality evidence that VDRAs effectively suppress PTH levels, but at the expense of increased risk of hypercalcaemia [2].

5. kidney-international.org kidney-international.org/article/S0085-2538(23)00540-9/fulltext

Vitamin D supplementation in people with chronic ... Vitamin D supplements have long been advocated for people with chronic kidney disease based on data from observational studies among the general population.