Chronic Kidney Disease, Coronary Artery Disease, Hypovitaminosis D, Secondary Hyperparathyroidism
Conditions
Keywords
Vitamin D, Coronary Artery Disease (CAD), Chronic Kidney Disease (CKD)
Brief summary
The purpose of this study is to determine if vitamin D supplementation changes the results of certain tests associated with inflammation in the body using an oral, synthetic form of vitamin D called paricalcitol.
Detailed description
Vitamin D deficiency is common and has been associated with an increased risk of heart disease. In patients with the combination of kidney disease and heart disease, inflammation is thought to contribute to a high rate of cardiac events. Less is known about the effects of vitamin D supplementation on certain tests associated with inflammation in the body.
Interventions
DRUGparicalcitol
2 mcg oral paricalcitol daily
DRUGplacebo
placebo
Sponsors
Abbott
Thomas Jefferson University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men and non-pregnant, non-lactating women greater than 18 years of age * Able to given informed consent and complete scheduled visits * History of established coronary artery disease (CAD)as defined by coronary stenosis in one or more vessels greater than or equal to 70% by coronary angiography or CT angiogram OR abnormal stress test (at least medium-sized, moderate reversible defect) OR a presence of a CAD risk equivalent as defined by the National Cholesterol Education Panel (NCEP)III as: Framingham risk score ≥ 20%, diabetes, or peripheral arterial disease(4) * High Sensitivity C-reactive Protein (hs-CRP) ≥ 2.0 mg/L * History of stage 3 or 4 chronic Kidney disease (CKD) defined as an glomerular filtration rate (eGRF) by the Modification of Diet in Renal Disease (MDRD) formula of 15-60 mL/min/1.73 m2 * Low level of serum 25-hydroxyvitamin D (\<30ng/mL) * Evidence of secondary hyperparathyroidism defined as intact parathyroid hormone (iPTH) level \> 70 pg/mL * Stable dose of statin and/or other lipid lowering therapy (ie: ezetimibe, fibrates, bile acid sequestrants nicotinic acid, fish oil) for 12 weeks prior to enrollment without known plans for change to current therapy during the study period
Exclusion criteria
* History of myocardial infarction, stroke, or cardiac surgery within 6 months of enrollment * History of carotid artery surgery * Planned cardiovascular surgery or procedure, with the exception of permanent pacemaker placement, in the next 18 months. * Use of vitamin D or calcium supplementation within the past 12 weeks with the exception of calcium containing phosphate binders and a daily multivitamin containing ≤ 400 IU of vitamin D * Hypercalcemia (as defined by the laboratory upper limit of normal ) or hyperphosphatemia (≥ 5.5 mg/dL) * Plan to initiate renal replacement therapy (dialysis) during the study * History of left ventricular systolic dysfunction with an ejection fraction \<50% or history of New York Heart Association (NYHA)functional Class II-IV congestive heart failure * Uncontrolled blood pressure, defined as systolic blood pressure greater than 160 mmHg and diastolic blood pressure greater than 100 mm Hg at the screening visit * Uncontrolled diabetes, defined as hemoglobin A1C ≥ 10.0 * History of any surgery within the past 3 months or known to be planned during the study period * History of malignancy within the past 5 years with the exception of non-melanoma (ie: squamous cell or basal cell) skin cancer * History of a known systemic or pulmonary inflammatory condition (including rheumatoid arthritis, systemic lupus erythematosus, chronic obstructive pulmonary disease, pulmonary fibrosis, sarcoidosis, Wegener's granulomatosis, Goodpasture's disease) * History of renal or other organ transplant and/or immunosuppressed state (ie immunosuppressive therapy or condition such as HIV) * History of any other condition, that in the opinion of the investigators renders it unsafe for the subject to be enrolled * For woman able to become pregnant, unwillingness to use birth control * Participation in another clinical trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in High Sensitivity-C Reactive Protein (Serum) | 1 year |
Secondary
| Measure | Time frame |
|---|---|
| Change in Markers of Inflammation Including Interleukin (IL)-1, IL-6, Tumor Necrosis Factor Alpha, Matrix Metalloproteinase (MMP) -9 and Serum Amyloid A | 1 year |
| Effect on Known Coronary Artery Disease Risk Factors Including Lipids and Blood Pressure. | 1 year |
| Effect on Carotid Intima-media Thickening (CIMT) | 1 year |
Countries
United States
Participant flow
Recruitment details
The enrollment period began in November 2009. The first subject was emrolled June 17, 2010. The final subject (#12) was enrolled April 14, 2011.
Pre-assignment details
2 additional participants were in a washout period when the study was stopped. These participants were not enrolled or randomized.
Participants by arm
| Arm | Count |
|---|---|
| Enrolled Total number participants consentedand enrolled | 10 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Trial was stopped before completed | 7 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Enrolled |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 6 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 4 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
Change in High Sensitivity-C Reactive Protein (Serum)
Time frame: 1 year
Population: Data were not collected when study was stopped prematurely.
Secondary
Change in Markers of Inflammation Including Interleukin (IL)-1, IL-6, Tumor Necrosis Factor Alpha, Matrix Metalloproteinase (MMP) -9 and Serum Amyloid A
Time frame: 1 year
Population: Data were not collected when study was stopped prematurely.
Secondary
Effect on Carotid Intima-media Thickening (CIMT)
Time frame: 1 year
Population: Data were not collected when study was stopped prematurely.
Secondary
Effect on Known Coronary Artery Disease Risk Factors Including Lipids and Blood Pressure.
Time frame: 1 year
Population: Data were not collected when study was stopped prematurely.