DePTH: De-emphasize PTH

Kidney Failure, Chronic Clinical Trial

Official title:

DePTH: De-emphasize Parathyroid Hormone

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06288451
• Other study ID #: STUDY00018021
• Secondary ID: 1K23DK136930-01
• Status: Recruiting
• Phase: Phase 2
• Start date: March 11, 2024
• Est. completion date: February 28, 2027

Study information

• Verified date: March 2024
• Source: University of Washington
• Contact: Simon Hsu, MD, MS
• Phone: (206) 616-5916
• Email: sihsu[@]uw.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: February 28, 2027
• Est. primary completion date: February 28, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Bone Diseases
• Chronic Kidney Disease-Mineral and Bone Disorder
• Kidney Diseases
• Kidney Failure, Chronic
• Renal Insufficiency
• Renal Insufficiency, Chronic

Intervention

Drug:
• Oral calcitriol with cinacalcet rescue
Participants will receive in-center oral calcitriol at a fixed dose of 0.5 mcg three times weekly at their dialysis treatment sessions regardless of their parathyroid hormone (PTH) concentrations over the 12-month trial period. Only if their serum PTH exceeds 800 pg/mL over 2 consecutive measurements will they be started on cinacalcet at 30 mg/d in order to protect against severe unremitting hyperparathyroidism.
• IV activated vitamin D
Participants will continue to receive intravenously-administered activated vitamin D per the Northwest Kidney Center treatment protocol, dose-titrated to monthly to quarterly parathyroid hormone concentrations.

Locations

Country	Name	City	State
United States	University of Washington	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
University of Washington	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Patient acceptability	Study acceptability to patients rated from 1 to 5 with 1 being the lowest acceptability and 5 being the highest	6 months
Other	Patient acceptability	Study acceptability to patients rated from 1 to 5 with 1 being the lowest acceptability and 5 being the highest	12 months
Primary	Change in fibroblast growth factor-23	Change in fibroblast growth factor-23	12 months
Secondary	Change in serum calcium	Change in serum calcium	12 months
Secondary	Change in serum phosphate	Change in serum phosphate	12 months
Secondary	Change in serum bone-specific alkaline phosphatase	Change in serum bone-specific alkaline phosphatase	12 months
Secondary	Change in serum parathyroid hormone	Change in serum parathyroid hormone	12 months
Secondary	Change in T50 test of serum calcification propensity	Change in T50 test of serum calcification propensity	12 months