DePTH: De-emphasize PTH

NCT ID: NCT06288451

Last Updated: 2025-06-02

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-11
• Study Completion Date: 2027-02-28

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.

Conditions

Kidney Failure, Chronic; Chronic Kidney Disease-Mineral and Bone Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Low dose oral calcitriol

Group Type: EXPERIMENTAL

Oral calcitriol with cinacalcet rescue

Intervention Type: DRUG

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.

Usual care

Group Type: ACTIVE_COMPARATOR

IV activated vitamin D

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

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

NIH

Sponsor Role: collaborator

University of Washington

OTHER

Sponsor Role: lead

Responsible Party

Simon Hsu, MD, MS

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Simon Hsu, MD, MS

Role: PRINCIPAL_INVESTIGATOR

University of Washington

Locations

University of Washington

Seattle, Washington, United States

Countries

United States

Other Identifiers

1K23DK136930-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY00018021

Identifier Type: -

Identifier Source: org_study_id