The Effects of Active VItamin D on Left Atrial Volume Index

• Status: Withdrawn
• Trial end date: 2014-06-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Massachusetts General Hospital
• Treatments: Ergocalciferols; Vitamin D; Vitamins

Criteria

Inclusion Criteria:

• Sign informed consent.

• Willing and able to adhere to all study-related procedures, including study medication regimen.

• ≥ 18 years old.

• Previous clinical diagnosis of heart failure with preserved ejection fraction: NYHA Class II-IV.

• Satisfy these echocardiographic criteria within the last year: Left ventricular ejection fraction ≥ 50%, cardiac magnetic resonance or ventriculogram; Left atrial size ≥ 4 cm in long axis or > 5.2 cm in four chamber length; Septal wall thickness > 1.2 cm (females) or 1.3 cm (males); Doppler evidence of moderate or severe diastolic dysfunction (≥ Grade II) by transmitral inflow, pulmonary venous flow, color M-mode and/or tissue Doppler (per European Society of Cardiology guidelines).

• Experienced ≥ 1 of the following in last 12 months: Hospitalization for acute heart failure (primary diagnosis); Long term treatment with loop diuretic; Mean pulmonary capillary wedge pressure ≥ 16 mm Hg at catheterization for dyspnea; Left ventricular end diastolic pressure (LVEDP) ≥ 19 mm Hg at catheterization for dyspnea; Acute treatment with intravenous loop diuretic or hemofiltration.

• On stable medical therapy in last 30 days before study entry (defined as no change in angiotensin converting enzyme inhibitors [ACEI], angiotensin receptor blockers, aldosterone inhibitors, beta-blockers or calcium channel blockers.

• Satisfy these criteria at initial lab screening: Estimated glomerular filtration rate (eGFR) ≥ 30 ml/min; Corrected serum Ca 8.0-10.0 mg/dL (2.0-2.5 mmol/L); Phos ≤ 5.2 mg/dL (1.68 mmol/L); Serum albumin ≥ 3.0 g/dL (30 g/L);

• Negative serum pregnancy test for females of childbearing potential (within 2 weeks of starting study treatment).

• Women of childbearing potential must be practicing barrier/oral contraception during study-related treatment, or be surgically sterile or one year post-menopausal, be non-nursing and non-pregnant.

Exclusion Criteria:

• Taking > 1,000 IU of vitamin D preparation daily within last 30 days.

• Received activated vitamin D preparation including paricalcitol (Zemplar®), doxercalciferol (Hectorol®) or calcitriol (Rocalctrol®, Calcijex®) within last 90 days prior to study entry.

• History of nephrolithiasis.

• Poorly controlled hypertension (systolic blood pressure > 180 mmHg and/or diastolic blood pressure > 110 mmHg at Screening; confirmed by repeat).

• Secondary hypertension (i.e. renal artery stenosis, primary aldosteronism or pheochromocytoma).

• Severe hepatic impairment.

• Use of known inhibitors (ie, ketoconazole) or inducers (ie, carbamazepine) of cytochrome P450 3A (CYP3A) within 2 weeks prior to taking study drug.

• HIV positive.

• Condition with prognosis < 1 year at study entry other than heart failure.

• Significant valvular disease defined as moderate or severe aortic or mitral stenosis, mitral or aortic regurgitation.

• Infiltrative cardiac disease (sarcoid, amyloid, hemochromatosis, lymphoma, etc.).

• Arrhythmogenic right ventricular cardiomyopathy.

• Active myocarditis.

• Constrictive or restrictive pericarditis.

• Acute coronary artery disease symptoms defined as emergency department visit or hospital admission with unstable angina, ST-elevation myocardial infarction (STEMI), non-ST-elevation myocardial infarction (NSTEMI), percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) within 90 days before study entry.

• Poor echocardiographic windows.

• Current active treatment in another investigational study or participation in another investigational study within 1 month before screening.

• Active malignancies except in situ carcinoma of the cervix, localized squamous or basal cell carcinoma of skin.

• Other serious concurrent or recent medical or psychiatric condition which, in Investigator's opinion, makes the patient unsuitable for participation.