Ergocalciferol Therapy in Calcidiol Deficient, Hemodialysis Patients on Therapeutic Doses of Paricalcitol

NCT ID: NCT02011828

Last Updated: 2016-08-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 58 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-05-31
• Study Completion Date: 2011-01-31

Brief Summary

The objective of this study is to determine the effects of cholecalciferol treatment on inflammation and insulin resistance, in patients on hemodialysis that are previously treated with paricalcitol.

Cholecalciferol is produced by the action of sunlight on a cholesterol precursor in the skin. This compound is then converted to calcidiol (25(OH) D3) in the liver, whereupon calcidiol is converted in the kidney to calcitriol (1,25(OH)2D3), the active form of vitamin D. However, recently it has been shown that deficiency of either calcidiol or calcitriol is associated with inflammation, insulin resistance and increased mortality in the general population. Furthermore, when both calcidiol and calcitriol were deficient, the mortality risk was much higher than the deficiency of either alone. A possible explanation is that some of the non-renal tissues might critically depend on the endogenous conversion of calcidiol to calcitriol and not on circulating levels of calcitriol. Thus, low circulating levels of calcidiol might be associated with tissue level functional calcitriol deficiency despite adequate circulating levels of calcitriol.

Therefore, the hypothesis is that:

1. In non-diabetic hemodialysis (HD) patients treated with therapeutic doses of paricalcitol (an analog of calcitriol), calcidiol deficiency is associated with inflammation and insulin resistance and

2. In calcidiol deficient, non-diabetic HD patients with inflammation and treated with therapeutic doses of paricalcitol, cholecalciferol will reverse the calcidiol deficiency and thereby, reduce inflammation and insulin resistance.

Interleulin-6 (IL-6) is thought to play a central role in insulin resistance by down-regulating glucose transporter-4 messenger RNA. Furthermore, IL-6 levels are significantly negatively associated with calcidiol levels, therefore will be measured as the primary outcome.

Conditions

Inflammation; Insulin Resistance

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Ergocalciferol, then Placebo

Participants first receive Ergocalciferol 50,000 international units (IU)/week for the first 12 weeks. After a 4 week wash-out period, they then receive matching placebo treatment for 12 weeks.

Group Type: EXPERIMENTAL

Ergocalciferol

Intervention Type: DRUG

50,000 IU/week

Placebo

Intervention Type: DRUG

Placebo tablet

Placebo, then Ergocalciferol

Participants first receive placebo treatment (matching ergocalciferol 50,000 IU/week) for the first 12 weeks. After a 4 week wash-out period, they then receive ergocalciferol 50,000 IU/week treatment for 12 weeks.

Group Type: EXPERIMENTAL

Ergocalciferol

Intervention Type: DRUG

50,000 IU/week

Placebo

Intervention Type: DRUG

Placebo tablet

Interventions

Ergocalciferol

50,000 IU/week

Intervention Type: DRUG

Placebo

Placebo tablet

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Non diabetic patients on HD, on stable dose of paricalcitol supplements for at least 3 months with iPTH in target range. Of the 60 patients enrolled in the observational component, those with high CRP (> 3 mg/dl) and calcidiol deficiency (< 15 ng/ml) will be eligible to participate in the interventional study.
• As the median CRP in the HEMO Study was 11 mg/L and > 80% of HD patients are calcidiol deficient [10], most of the screened patients will be eligible. In each year, the first 12 patients who meet the above criteria and consent for the interventional component, a randomized cross-over trial of cholecalciferol 50,000 IU/ week vs. matching placebo will be conducted.

Exclusion Criteria

• Diabetic patients, not on paricalcitol, enrolled in other interventional studies, hospitalized in the past month or treated for an infection in the past month and pregnancy.
• We will conduct a pregnancy test for women in the reproductive age group (18-55 years) during the initial screening process. We will obtain serum β-HCG levels to rule out pregnancy and the test will be paid for by the study. The results will be reviewed by the PI. If β-HCG levels are positive these patients will be withdrawn from the study.

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

Sponsors

University of Utah

OTHER

Sponsor Role: lead

Responsible Party

Srinvasan Beddhu

MD, Associate Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Srinivasan Beddhu, MD

Role: PRINCIPAL_INVESTIGATOR

University of Utah

Vidya Raj Krishnamurthy, MD

Role: PRINCIPAL_INVESTIGATOR

University of Utah

Locations

University of Utah

Salt Lake City, Utah, United States

Countries

United States

Other Identifiers

IRB_00032685

Identifier Type: -

Identifier Source: org_study_id