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

NCT02011828 | Completed Phase 1 DMC

• 1 other identifier: IRB_00032685
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

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. 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. 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.

Conditions

Inflammation; Insulin Resistance

Keywords

Hemodialysis, paricalcitol

Outcome Measures

Primary Outcomes (1)

• Plasma concentration of Interleukin-6 (IL-6)

  Comparison of IL-6 levels after treatment with ergocalciferol and after treatment with placebo

  28 weeks

Study Arms (2)

Ergocalciferol, then Placebo

EXPERIMENTAL

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.

Drug: Ergocalciferol; Drug: Placebo

Placebo, then Ergocalciferol

EXPERIMENTAL

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.

Drug: Ergocalciferol; Drug: Placebo

Interventions

Ergocalciferol DRUG

50,000 IU/week

Ergocalciferol, then Placebo; Placebo, then Ergocalciferol

Placebo DRUG

Placebo tablet

Ergocalciferol, then Placebo; Placebo, then Ergocalciferol

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Utah: lead

Study Sites (1)

University of Utah

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Inflammation; Insulin Resistance

Interventions

Ergocalciferols

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids

Study Officials

• Srinivasan Beddhu, MD

  University of Utah

  PRINCIPAL INVESTIGATOR

• Vidya Raj Krishnamurthy, MD

  University of Utah

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Associate Professor of Medicine

Study Record Dates

• First Submitted: June 13, 2012
• First Posted: December 13, 2013
• Study Start: May 1, 2009
• Primary Completion: January 1, 2011
• Study Completion: January 1, 2011
• Last Updated: August 11, 2016

Record last verified: 2016-08

Locations

US (1)