Clinical trial NCT06288451: DePTH: De-emphasize PTH
Official title: DePTH: De-emphasize Parathyroid Hormone
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Kidney Failure, Chronic
Chronic Kidney Disease-Mineral and Bone Disorder
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2024-03-01
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

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

Primary outcomes:
measure: Change in fibroblast growth factor-23
timeFrame: 12 months
Secondary outcomes:
measure: Change in serum calcium
timeFrame: 12 months
measure: Change in serum phosphate
timeFrame: 12 months
measure: Change in serum bone-specific alkaline phosphatase
timeFrame: 12 months
measure: Change in serum parathyroid hormone
timeFrame: 12 months
measure: Change in T50 test of serum calcification propensity
timeFrame: 12 months
Other outcomes:
measure: Patient acceptability
timeFrame: 6 months
measure: Patient acceptability
timeFrame: 12 months
Locations:
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: University of Washington
name: Simon Hsu, MD, MS
role: PRINCIPAL_INVESTIGATOR
References: