The Effects of Active VItamin D on Left Atrial Volume Index (AVID-LAVI)
This is a pilot feasibility study to determine the effects of an activated vitamin D compound (paricalcitol) on heart structure (size) and function (ability to relax) in patients with normal kidney function and a form of heart failure known as HFPEF (heart failure and preserved ejection fraction). This study will also examine heart failure-related hospitalizations and changes in cardiac-stretch and biological markers that are believed to change along with heart size. Patients in this pilot study will be treated for a period of 48 weeks with paricalcitol at a dose previously approved by FDA (1 mcg per day) and followed-up for 4 weeks after treatment is completed.
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Pilot Study of the Effects of Active VItamin D on Left Atrial Volume Index in Patients With Heart Failure and Preserved Ejection Fraction|
- Change in left atrial volume index (LAVI) by transthoracic echocardiography. [ Time Frame: Baseline and Week 48 ] [ Designated as safety issue: No ]The analysis will include all patients with at least two echocardiographic studies (baseline and one follow up). The primary endpoint will be determined upon completion of the study (ie, when all enrolled patients have been treated for up to 48 weeks with study medication).
- Number of and time-to-first heart failure-related hospitalizations [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
- Overall cardiac and non-cardiac mortality rates [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
- Changes in biological, inflammatory, LVH and strain biomarkers that have been linked to cardiovascular disease. [ Time Frame: Baseline and 48 weeks ] [ Designated as safety issue: No ]High-sensitivity troponin-T, NT-proBNP, high-sensitivity C-reactive protein, propeptide procollagen type I, ST-2, Galectin-3, GDF-15 and osteoprotegerin
- Changes in standard mineral metabolite parameters (calcium, phosphorus, calcium-phosphate-product and PTH) [ Time Frame: Baseline and 48 weeks ] [ Designated as safety issue: No ]
- Changes in self-reported Patient Global Assessment [ Time Frame: Baseline and 48 weeks ] [ Designated as safety issue: No ]
- Change in diastolic function parameters (including E, A, IVRT, DT) [ Time Frame: Baseline and Week 48 ] [ Designated as safety issue: No ]
- Change in tissue doppler parameters (including Ea, Aa) [ Time Frame: Baseline and Week 48 ] [ Designated as safety issue: No ]
- Change in pulmonary venous inflow (including S, D, a reversal) [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
- Change in cardiac ejection fraction [ Time Frame: Baseline and Week 48 ] [ Designated as safety issue: No ]
- Change in end-diastolic and end-systolic left ventricular internal dimension [ Time Frame: Baseline and Week 48 ] [ Designated as safety issue: No ]
|Study Start Date:||March 2014|
|Estimated Study Completion Date:||June 2014|
|Estimated Primary Completion Date:||May 2014 (Final data collection date for primary outcome measure)|
Paricalcitol oral capsules (1 mcg per day for 48 weeks)
Paricalcitol oral capsules 1 mcg/day for 48 weeks
Other Name: Zemplar®
Heart failure (HF) is among the top ten causes of hospitalizations in the US. It is estimated that ~40-50% of patients with HF have preserved ejection fraction (EF). Patients with heart failure and preserved ejection fraction (HFPEF) have normal systolic function, but impaired cardiac relaxation. The main causes of HFPEF include left-ventricular hypertrophy (LVH) and hypertension, hypertrophic cardiomyopathy, aortic stenosis with a normal EF, coronary artery disease and restrictive cardiomyopathies.
Only a few small clinical trials have tested therapeutic interventions in patients with HFPEF, producing either small or negative effects. Relatively few drugs have effects on cardiac relaxation and are not candidates for chronic use, as they may have significant side effect profiles and/or are inconvenient to administer. Paricalcitol, an FDA-approved activated form of vitamin D, has been shown to slow LVH progression and improve parameters associated with diastolic function in animal models (see refs). Treatment with paricalcitol has also been associated with decreased cardiovascular morbidity and mortality in a historical cohort study of patients with end-stage renal disease (see refs).
This is a single-center, single-arm, pilot study in 20 patients with HFPEF and normal renal function on stable medical therapy to evaluate the effects of paricalcitol on cardiac structure and function.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01630408
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 01886|
|Principal Investigator:||Hector Tamez, MD, MPH||Massachusetts General Hospital|
|Principal Investigator:||Ravi Thadhani, MD, MPH||Massachusetts General Hospital|