DePTH: De-emphasize PTH

Phase 2

Recruiting

• Conditions: Kidney Failure, Chronic; Chronic Kidney Disease-Mineral and Bone Disorder
• Interventions: Drug: Oral calcitriol with cinacalcet rescue; Drug: IV activated vitamin D

• Registration Number: NCT06288451
• Lead Sponsor: University of Washington

Brief Summary

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).

Detailed Description

Because of the kidneys' major role in vitamin D metabolism, most patients with kidney failure on dialysis have biochemical abnormalities that include vitamin D deficiency and high levels of phosphate, fibroblast growth factor-23 (FGF-23), and parathyroid hormone (PTH). All of these abnormalities are associated with cardiovascular disease, bone disease, and death and are major reasons why nephrologists have treated patients on dialysis with activated vitamin D agents for over 30 years. Current guidelines, however, encourage nephrologists to use high doses of vitamin D in order to lower PTH levels to pre-specified treatment targets. This approach to treatment has not been proven to improve health and survival, and may be associated with several harms, including further increasing levels of FGF-23 (a major cardiovascular risk factor), increasing calcium levels, which may promote vascular calcification, low turnover bone disease, and interruptions in vitamin D treatments.

Administering a low, stable dose of vitamin D may be safer and more effective than the current standard of care. The De-emphasize PTH (DePTH) Study is a pragmatic randomized clinical trial of 90 patients on hemodialysis in Seattle, WA, USA that tests whether a low fixed-dose of oral calcitriol (the active form of vitamin D; study intervention) is more safe, effective, and feasible compared with the current usual care. Participants will be recruited at their hemodialysis treatment centers and randomized in a 1:1 ratio to one of these two treatment strategies and followed over 12 months. Participants randomized to the study intervention will receive a fixed dose of calcitriol 0.5 mcg three times a week at their dialysis treatment sessions regardless of PTH level over the ensuing 12 months. Participants randomized to usual care will maintain the existing approach to treating abnormal mineral metabolism using vitamin D doses titrated to monthly to quarterly measurements of PTH. The outcomes for this trial are a panel of blood-based measurements of bone and vascular health that will be drawn at the same time as the blood work done monthly as part of routine dialysis care.

Study Timeline

• Study First Submitted: 2024-02-23
• Study First Submitted QC: 2024-02-23
• Study First Posted: 2024-03-01
• Study Start: 2024-03-11
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-12
• Last Update Posted: 2024-06-14
• Primary Completion: 2027-02-28
• Study Completion: 2027-02-28

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 90

Inclusion Criteria

1. Age >=18 years
2. Kidney failure treated with in-center hemodialysis
3. PTH >=150 pg/mL x 2 consecutive measures at least 1 month apart or active IV activated vitamin D treatment using the NKC protocol

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Exclusion Criteria

1. History of parathyroidectomy or calciphylaxis
2. 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)
3. Calcium >9.8 mg/dL
4. Phosphate >9 mg/dL
5. Cholestyramine, phenytoin/phenobarbital, or ketoconazole use
6. Breast-feeding mothers
7. Inability to provide informed consent and no legally authorized representative

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Low dose oral calcitriol	Oral calcitriol with cinacalcet rescue	-
Usual care	IV activated vitamin D	-

Primary Outcome Measures

Name	Time	Method
Change in fibroblast growth factor-23	12 months	Change in fibroblast growth factor-23

Secondary Outcome Measures

Name	Time	Method
Change in serum phosphate	12 months	Change in serum phosphate
Change in serum bone-specific alkaline phosphatase	12 months	Change in serum bone-specific alkaline phosphatase
Change in serum parathyroid hormone	12 months	Change in serum parathyroid hormone
Change in serum calcium	12 months	Change in serum calcium
Change in T50 test of serum calcification propensity	12 months	Change in T50 test of serum calcification propensity

Trial Locations

Locations (1)

University of Washington; 🇺🇸 Seattle, Washington, United States