Heart FailureAVID-LAVINCT01630408
The Effects of Active VItamin D on Left Atrial Volume Index
A study testing Paricalcitol in people with Heart Failure, run by Massachusetts General Hospital at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure
- What is being tested?
- Paricalcitol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2014to Jun 2014
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 01886
About this study
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
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.
Read the detailed description
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.
- Conditions
- Heart Failure
- Being tested
- Paricalcitol
- Keywords
- Preserved ejection fraction, Left ventricular hypertrophy, Activated vitamin D, Cardiac lusitropic effect, Hospitalizations
- Medical subject headings
- Heart Failure, Hypertrophy, Left Ventricular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ParicalcitolDrug
Also called Zemplar®
Paricalcitol oral capsules 1 mcg/day for 48 weeks
| Study group | Role | What they receive |
|---|---|---|
| Paricalcitol | Experimental | Paricalcitol oral capsules (1 mcg per day for 48 weeks) Receives: Drug: Paricalcitol |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Baseline and Week 48
Secondary outcomes (10)
Number of and time-to-first heart failure-related hospitalizations
Measured: 52 weeks
Overall cardiac and non-cardiac mortality rates
Measured: 52 weeks
Changes in biological, inflammatory, LVH and strain biomarkers that have been linked to cardiovascular disease.
High-sensitivity troponin-T, NT-proBNP, high-sensitivity C-reactive protein, propeptide procollagen type I, ST-2, Galectin-3, GDF-15 and osteoprotegerin
Measured: Baseline and 48 weeks
Changes in standard mineral metabolite parameters (calcium, phosphorus, calcium-phosphate-product and PTH)
Measured: Baseline and 48 weeks
Changes in self-reported Patient Global Assessment
Measured: Baseline and 48 weeks
Change in diastolic function parameters (including E, A, IVRT, DT)
Measured: Baseline and Week 48
Change in tissue doppler parameters (including Ea, Aa)
Measured: Baseline and Week 48
Change in pulmonary venous inflow (including S, D, a reversal)
Measured: Baseline to Week 48
Change in cardiac ejection fraction
Measured: Baseline and Week 48
Change in end-diastolic and end-systolic left ventricular internal dimension
Measured: Baseline and Week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jun 2012 (estimated)
- Study startMar 2014
- Primary completionMay 2014 (estimated)
- Study completionJun 2014 (estimated)
Why it stopped: Investigator decided not to pursue.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ravi Thadhani, Massachusetts General Hospital
- Investigators
- Hector Tamez, MD, MPH, Principal investigator, Massachusetts General HospitalRavi Thadhani, MD, MPH, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01630408
- Sponsor's protocol ID
- AVID-LAVI
- Acronym
- AVID-LAVI
- Status last verified
- Aug 2013
- First submitted
- 26 Jun 2012
- Last updated
- 16 Aug 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 17942703Wu 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.
PubMed 8601621Weishaar RE, Simpson RU. Vitamin D3 and cardiovascular function in rats. J Clin Invest. 1987 Jun;79(6):1706-12. doi: 10.1172/JCI113010.
PubMed 3034981Teng 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.
PubMed 12890843
Study at a glance
From the registry record, last updated by the sponsor on 16 Aug 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01630408
- Acronym / sponsor ID
- AVID-LAVI / AVID-LAVI
- Conditions
- Heart Failure
- Keywords
- Preserved ejection fraction, Left ventricular hypertrophy, Activated vitamin D, Cardiac lusitropic effect, Hospitalizations
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Investigator decided not to pursue.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- Mar 2014
- Primary completion
- May 2014 (estimated)
- Study completion
- Jun 2014 (estimated)
- First posted
- 28 Jun 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Paricalcitol | Experimental | Drug: ParicalcitolParicalcitol oral capsules (1 mcg per day for 48 weeks) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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).
Key exclusion criteria (19 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ParicalcitolAlso: Zemplar®Paricalcitol oral capsules 1 mcg/day for 48 weeks | Drug | Paricalcitol |
Primary outcome
Change in left atrial volume index (LAVI) by transthoracic echocardiography.
Time frame: Baseline and Week 48
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).
10 secondary outcomes
Number of and time-to-first heart failure-related hospitalizations
Time frame: 52 weeks
Overall cardiac and non-cardiac mortality rates
Time frame: 52 weeks
Changes in biological, inflammatory, LVH and strain biomarkers that have been linked to cardiovascular disease.
Time frame: Baseline and 48 weeks
Changes in standard mineral metabolite parameters (calcium, phosphorus, calcium-phosphate-product and PTH)
Time frame: Baseline and 48 weeks
Changes in self-reported Patient Global Assessment
Time frame: Baseline and 48 weeks
Change in diastolic function parameters (including E, A, IVRT, DT)
Time frame: Baseline and Week 48
Change in tissue doppler parameters (including Ea, Aa)
Time frame: Baseline and Week 48
Change in pulmonary venous inflow (including S, D, a reversal)
Time frame: Baseline to Week 48
Change in cardiac ejection fraction
Time frame: Baseline and Week 48
Change in end-diastolic and end-systolic left ventricular internal dimension
Time frame: Baseline and Week 48
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Aug 2013.
- Background: PubMed 17942703Bodyak 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.
- Background: PubMed 8601621Wu 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.
- Background: PubMed 3034981Weishaar RE, Simpson RU. Vitamin D3 and cardiovascular function in rats. J Clin Invest. 1987 Jun;79(6):1706-12. doi: 10.1172/JCI113010.
- Background: PubMed 12890843Teng 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hector Tamez, MD, MPH principal investigator
Massachusetts General Hospital
Ravi Thadhani, MD, MPH principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Paricalcitol in people with Heart Failure, run by Massachusetts General Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 16 Aug 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in left atrial volume index (LAVI) by transthoracic echocardiography. (time frame: Baseline and Week 48). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01630408, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Aug 2013.