The Effects of Active VItamin D on Left Atrial Volume Index

NCT01630408 | Withdrawn

• 1 other identifier: AVID-LAVI
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Heart Failure

Keywords

Preserved ejection fraction; Left ventricular hypertrophy; Activated vitamin D; Cardiac lusitropic effect; Hospitalizations

Outcome Measures

Primary Outcomes (1)

• Change in left atrial volume index (LAVI) by transthoracic echocardiography.

  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).

  Baseline and Week 48

Secondary Outcomes (10)

• Number of and time-to-first heart failure-related hospitalizations

  52 weeks

• Overall cardiac and non-cardiac mortality rates

  52 weeks

• Changes in biological, inflammatory, LVH and strain biomarkers that have been linked to cardiovascular disease.

  Baseline and 48 weeks

• Changes in standard mineral metabolite parameters (calcium, phosphorus, calcium-phosphate-product and PTH)

  Baseline and 48 weeks

• Changes in self-reported Patient Global Assessment

  Baseline and 48 weeks

Study Arms (1)

Paricalcitol

EXPERIMENTAL

Paricalcitol oral capsules (1 mcg per day for 48 weeks)

Drug: Paricalcitol

Interventions

Paricalcitol DRUG

Paricalcitol oral capsules 1 mcg/day for 48 weeks

Also known as: Zemplar®

Paricalcitol

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 01886, United States

Location

Related Publications (4)

• Bodyak N, Ayus JC, Achinger S, Shivalingappa V, Ke Q, Chen YS, Rigor DL, Stillman I, Tamez H, Kroeger PE, Wu-Wong RR, Karumanchi SA, Thadhani R, Kang PM. Activated vitamin D attenuates left ventricular abnormalities induced by dietary sodium in Dahl salt-sensitive animals. Proc Natl Acad Sci U S A. 2007 Oct 23;104(43):16810-5. doi: 10.1073/pnas.0611202104. Epub 2007 Oct 17.

  PMID: 17942703 BACKGROUND

• Wu J, Garami M, Cheng T, Gardner DG. 1,25(OH)2 vitamin D3, and retinoic acid antagonize endothelin-stimulated hypertrophy of neonatal rat cardiac myocytes. J Clin Invest. 1996 Apr 1;97(7):1577-88. doi: 10.1172/JCI118582.

  PMID: 8601621 BACKGROUND

• Weishaar RE, Simpson RU. Vitamin D3 and cardiovascular function in rats. J Clin Invest. 1987 Jun;79(6):1706-12. doi: 10.1172/JCI113010.

  PMID: 3034981 BACKGROUND

• Teng M, Wolf M, Lowrie E, Ofsthun N, Lazarus JM, Thadhani R. Survival of patients undergoing hemodialysis with paricalcitol or calcitriol therapy. N Engl J Med. 2003 Jul 31;349(5):446-56. doi: 10.1056/NEJMoa022536.

  PMID: 12890843 BACKGROUND

MeSH Terms

Conditions

Heart Failure; Hypertrophy, Left Ventricular

Interventions

paricalcitol

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Cardiomegaly; Hypertrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Study Officials

• Hector Tamez, MD, MPH

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

• Ravi Thadhani, MD, MPH

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Clinical Research in Nephrology

Study Record Dates

• First Submitted: June 26, 2012
• First Posted: June 28, 2012
• Study Start: March 1, 2014
• Primary Completion: May 1, 2014
• Study Completion: June 1, 2014
• Last Updated: August 16, 2013

Record last verified: 2013-08

Locations

US (1)