Mineral Metabolism and Vascular Effects of Vitamin D Therapy in Kidney Transplant Patients

Hyperparathyroidism, Secondary Clinical Trial

— PAD  

Official title:

Mineral Metabolism and Vascular Effects of Vitamin D Therapy in Kidney

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00646282
• Other study ID #: IRB00006614
• Status: Terminated
• Phase: Phase 4
• First received: March 25, 2008
• Last updated: January 14, 2015
• Start date: April 2008
• Est. completion date: January 2010

Study information

• Verified date: January 2015
• Source: Emory University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Patients with kidney failure on dialysis can be successfully transplanted. However, many of them do not attain a normal kidney function and/or present a slow deterioration of kidney function after transplantation. As a consequence, they can develop an endocrine disorder called hyperparathyroidism, which can cause bone disease and a high risk of bone fractures. In spite of the known bone disease and hyperparathyroidism, there is no well defined treatment for these patients.

Moreover, kidney transplant recipients present a higher mortality rate compared to the general population, and the principal cause of death is cardiovascular disease. Dialysis patients are known to have extensive cardiovascular calcifications and increased vascular stiffness, and these factors have been closely associated with cardiovascular mortality.

The effect of vitamin D on bone health is well known in the general population. Many studies showed a reduction in fracture rate in post-menopausal women and older men receiving vitamin D and calcium supplements. Vitamin D analogues are also commonly used to treat hyperparathyroidism in dialysis patients. Finally, vitamin D has been suggested to have beneficial effects on the cardiovascular system and to reduce mortality in dialysis patients.

Hectorol® is a vitamin D analog which has been demonstrated to effectively treat hyperparathyroidism in dialysis and pre-dialysis patients.

The effects of vitamin D supplementation on bone disease, hyperparathyroidism and cardiovascular function in kidney transplant recipients have not been properly studied.

Whether Hectorol® therapy helps reducing the severity of bone disease and improving vascular function in kidney transplant recipients is still unknown.

Description:

The investigators plan to study the cardiovascular and bone effects of Hectorol® in 100 kidney transplant recipients. The kidney transplant patients will be screened for kidney transplant dysfunction and hyperparathyroidism. The study medication will be given to 50 patients. The other 50 patients will continue to be treated with the actual standard of care at the transplant clinic. Subjects will be followed for 18 months and their laboratory values, bone density, vascular calcification and stiffness will be collected to see if there is an effect of Hectorol® compared to the actual standard of care.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 12
• Est. completion date: January 2010
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Kidney transplant recipient > 18 year/old with reduced and stable kidney function (estimated GFR 25-60 ml/min/1.73m2)

• iPTH levels between 120 and 500 pg/ml

• Stable immunosuppressive therapy (5-10 mg Prednisone/day, stable dosage of calcineurin inhibitors, or other immunosuppressive agents for at least 6 months)

Exclusion Criteria:

• Recent rejection episode (< 3 months)

• One of the following: baseline estimated GFR>60 ml/min/1.73m2 or <25 ml/min/1.73m2, albumin-corrected Ca>9.5 mg/dl or serum phosphorus >4.6 mg/dl.

• Recipients of dual transplant organs with exception of kidney-pancreas

• Patients already receiving treatment with Vitamin D analogues

• Severe peripheral vascular disease or coronary artery disease

• History of previous parathyroidectomy

• Current alcohol or drug abuse

• Pregnant or nursing woman or female of child-bearing age not receiving contraception

• Other comorbidities that in the opinion of the investigators would reduce expected patient's survival and preclude study completion

• Medications that could interfere with Hectorol® metabolism

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hyperparathyroidism
• Hyperparathyroidism, Secondary

Intervention

Drug:
• doxercalciferol
The study drug dosage will be initiated according to baseline iPTH levels. For patients with iPTH>300 pg/ml, oral Doxercalciferol will be given at 1 mcg/day; for patients with iPTH <300 pg/ml, oral Doxercalciferol will be initiated at 0.5 mcg/day.

Locations

Country	Name	City	State
United States	Emory University	Atlanta	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
Emory University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Subjects With 50% Reduction of Intact Parathyroid Hormone (iPTH) Levels	Number of participants that have 50% reduction in iPTH levels (but not lower than 65 pg/ml) at 18 months	18 months	No