Chronic Heart FailurePhase 2VitD-CHFNCT01092130
Study to Investigate the Effects of Vitamin D Administration on Plasma Renin Activity in Patients With Stable Chronic Heart Failure
A Phase 2 study testing Vitamin D in people with Chronic Heart Failure, run by University Medical Center Groningen at 1 site in Netherlands.
Trial summary
The renin-angiotensin system (RAS) is a regulatory system that plays an essential role in patients with chronic heart failure (CHF). Plasma renin activity (PRA) is a strong and independent predictor of outcome, also in the presence of ACE inhibitors (ACE-i) and/or angiotensin receptor blockers (ARBs). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Heart Failure
- What is being tested?
- Vitamin D
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 101 participants
- Where
- 1 siteNetherlands
- Study dates
- Mar 2010to Sep 2012
- Phase
- Phase 2
- 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
- Out clinical patients ≥ 18 years of age, male or female.
- Patients with a diagnosis of chronic heart failure (NYHA Class II, III or IV).
- Patients must at least be treated with an ACE-i at a stable dose (at least enalapril 10 mg daily or any other ACE-i, e.g. ramipril, quinapril, lisinopril, fosinopril, perindopril, trandolapril; on equivalent doses, or maximum tolerated dose) or if intolerant to ACE-i with ARB therapy (Candesartan 8 mg daily or any other ARB in equivalent dose, or maximum tolerated dose) for at least 4 weeks prior to visit 1.
- Patients must be treated with a beta blocker unless contraindicated or not tolerated at a stable dose for at least 4 weeks prior to visit 1 (for patients not on target dose or in absence of that medication, the reason should be documented).
- Concomitant use of ACE-i and/or ARB and/or aldosterone antagonist is permitted.
Who cannot join
- LVEF >45% at visit 1 (local measurement, measured within the past 12 months assessed by echocardiogram, MUGA or ventricular angiography).
- History of hypersensitivity to the study drugs.
- Patients with phenylketonuria.
- Patients with fructose intolerance.
- Current acute decompensated heart failure.
- Hypercalcemia (>2.65 mmol/l, corrected for albumin).
Show all 36Show fewer
- Hypercalciuria.
- Estimated glomerular filtration fraction (eGFR) between 30 and 60 ml/min/1.73m2 as measured by the modified of diet in renal disease (MDRD) formula.
- Nephrolithiasis.
- Sarcoidosis.
- Use of the following medication: corticosteroids, thyroxin, anti epileptic drugs, tetracyclines, quinolones
- Intake of supplements containing vitamin D and/or calcium.
- Acute coronary syndrome, stroke, transient ischemic attack, cardiac, carotid or major vascular surgery, percutaneous coronary intervention (PCI) or carotid angioplasty, within the past 3 months.
- Coronary or carotid artery disease likely to require surgical or PCI.
- Right heart failure due to severe pulmonary disease.
- Diagnosis of peripartum or chemotherapy induced cardiomyopathy within the last year.
- Patients with a history of heart transplant or who are on a transplant list or with LVAD device (left ventricular assistance device).
- Documented ventricular arrhythmia with syncopal episodes within past 3 months that is untreated.
- Documented history of ventricular tachycardia or ventricular fibrillation without ICD (internal cardiac defibrillator).
- Symptomatic bradycardia, or second or third degree heart block without a pacemaker.
- Implantation of a CRT (cardiac resynchronization therapy) device within prior 3 months.
- Presence of hemodynamically significant mitral and /or aortic valve disease, except mitral regurgitation secondary to left ventricular dilatation.
- Presence of hemodynamically significant obstructive lesions of left ventricular outflow tract, including aortic stenosis.
- Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of study drugs.
- Any history of pancreatic injury, pancreatitis or evidence of impaired pancreatic function/injury as indicated by abnormal lipase or amylase.
- Primary liver disease considered to be life threatening.
- Currently active gastritis, duodenal or gastric ulcers, or gastrointestinal/rectal bleeding during the 3 months prior to Visit 1.
- History or presence of any other diseases (i.e. including malignancies) with a life expectancy of < 5 years.
- Current double-blind treatment in heart failure (HF) trials.
- Participation in an investigational drug study at the time of enrollment or within the past 30 days or 5 half lives of enrollment whichever is longer.
- Any surgical or medical condition that in the opinion of the investigator or medical monitor would jeopardize the evaluation of efficacy or safety.
- History of noncompliance to medical regimens and patients who are considered potentially unreliable.
- Pregnant or lactating women.
- Treatment with any of the following drugs within the past 4 weeks prior to Visit 1 (T0):
- Direct renin inhibition including Aliskiren
- Intravenous vasodilator and/or inotropic drugs
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
University Medical Center Groningen
Groningen, Provincie Groningen, 9700 RB
About this study
Official title: An Open-label, Blinded-endpoint, Randomized, Prospective Trial Investigating the Effects of Vitamin D Administration on Plasma Renin Activity in Patients With Stable Chronic Heart Failure
The renin-angiotensin system (RAS) is a regulatory system that plays an essential role in patients with chronic heart failure (CHF). Plasma renin activity (PRA) is a strong and independent predictor of outcome, also in the presence of ACE inhibitors (ACE-i) and/or angiotensin receptor blockers (ARBs). Recently, it has been shown that vitamin D regulates renin transcription by activating the vitamin D receptor (VDR). Thus, specific activation of the VDR represents a novel target for therapeutic intervention in CHF. Currently, clinical data are lacking. The investigators aim to investigate the effect of the administration of vitamin D in patients with CHF.
- Conditions
- Chronic Heart Failure
- Being tested
- Vitamin D
- Keywords
- Heart failure, Vitamin D, Plasma renin activity, Renin angiotensin system
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vitamin DDrug
Also called Colecalciferol
2000 IU vitamin D daily, for 6 weeks
| Study group | Role | What they receive |
|---|---|---|
| Vitamin D | Experimental | Patients were randomized by an automated computer system to 2000 IU oral cholecalciferol once daily or control (i.e. no extra medication), in a 1:1 ratio for a period of six weeks. Blood was collected in a sitting position on visits 2-4 and patients were asked to collect 24h urine samples prior to visits 2 and 4. Heart failure medication was maintained unchanged throughout the trial. Changes in diuretic dose were permitted if necessary to treat decompensation or renal dysfunction. Receives: Drug: Vitamin D |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma Renin Activity
The primary endpoint of this study is the PRA after 6 weeks of treatment with vitamin D compared to the PRA after 6 weeks without treatment.
Measured: 6 weeks
Secondary outcomes (7)
Safety endpoints are biochemical indices of kidney function and bone homeostasis
Measured: 6 weeks
To evaluate the effect of vitamin D administration on plasma values of additional markers of renin-angiotensin system activity, including angiotensin II, angiotensin converting enzyme activity and chymase activity
Measured: 6 weeks
To evaluate the effect of vitamin D administration on different markers of the vitamin D cascade, such as vitamin D, calcium, phosphate and PTH (parathyroid hormone)
Measured: 6 weeks
To evaluate the effect of vitamin D administration on plasma levels of NT-proBNP
Measured: 6 weeks
To evaluate the effect of vitamin D administration on urinary levels of markers of glomerular and tubular damage
Measured: 6 weeks
To evaluate the effect of vitamin D administration on extracellular matrix markers (PIIINP, PICP, PINP) and degradation markers (MMP1, MMP9, TIMP1, MMP1/TIMP1-complex)
Measured: 6 weeks
To evaluate the effect of vitamin D administration on NYHA-class
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2010 (estimated)
- Study startMar 2010
- Primary completionMar 2012
- Study completionSep 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Heart FailureStudies of the same condition, open and under way.
- More trials run by University Medical Center GroningenThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 101 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Medical Center Groningen
- Sponsor type
- University, hospital or other
- Collaborators
- Netherlands Foundation for Cardiovascular Excellence
- Responsible party
- Principal investigator, Willem-Peter Theodoor Ruifrok, University Medical Center Groningen
- Investigators
- W. T. Ruifrok, MD, Principal investigator, University Medical Center GroningenR. A. de Boer, MD, PhD, Study director, University Medical Center GroningenW. H. van Gilst, PhD, Study chair, University Medical Center Groningen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01092130
- Sponsor's protocol ID
- WTR-ECG-4
- Acronym
- VitD-CHF
- Status last verified
- Feb 2013
- First submitted
- 12 Mar 2010
- Last updated
- 15 Feb 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Schroten NF, Ruifrok WP, Kleijn L, Dokter MM, Sillje HH, Lambers Heerspink HJ, Bakker SJ, Kema IP, van Gilst WH, van Veldhuisen DJ, Hillege HL, de Boer RA. Short-term vitamin D3 supplementation lowers plasma renin activity in patients with stable chronic heart failure: an open-label, blinded end point, randomized prospective trial (VitD-CHF trial). Am Heart J. 2013 Aug;166(2):357-364.e2. doi: 10.1016/j.ahj.2013.05.009. Epub 2013 Jun 24.
PubMed 23895820
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Blinded-endpoint, Randomized, Prospective Trial Investigating the Effects of Vitamin D Administration on Plasma Renin Activity in Patients With Stable Chronic Heart Failure
- ClinicalTrials.gov ID
- NCT01092130
- Acronym / sponsor ID
- VitD-CHF / WTR-ECG-4
- Conditions
- Chronic Heart Failure
- Keywords
- Heart failure, Vitamin D, Plasma renin activity, Renin angiotensin system
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 101 participants (actual)
- Lead sponsor
- University Medical Center GroningenUniversity, hospital or other
- Collaborators
- Netherlands Foundation for Cardiovascular Excellence
- Study start
- Mar 2010
- Primary completion
- Mar 2012 (actual)
- Study completion
- Sep 2012 (actual)
- First posted
- 24 Mar 2010 (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.
The renin-angiotensin system (RAS) is a regulatory system that plays an essential role in patients with chronic heart failure (CHF). Plasma renin activity (PRA) is a strong and independent predictor of outcome, also in the presence of ACE inhibitors (ACE-i) and/or angiotensin receptor blockers (ARBs). Recently, it has been shown that vitamin D regulates renin transcription by activating the vitamin D receptor (VDR). Thus, specific activation of the VDR represents a novel target for therapeutic intervention in CHF. Currently, clinical data are lacking. The investigators aim to investigate the effect of the administration of vitamin D in patients with CHF.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Vitamin D | Experimental | Drug: Vitamin DPatients were randomized by an automated computer system to 2000 IU oral cholecalciferol once daily or control (i.e. no extra medication), in a 1:1 ratio for a period of six weeks. Blood was collected in a sitting position on visits 2-4 and patients were asked to collect 24h urine samples prior to visits 2 and 4. Heart failure medication was maintained unchanged throughout the trial. Changes in diuretic dose were permitted if necessary to treat decompensation or renal dysfunction. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Out clinical patients ≥ 18 years of age, male or female.
- Patients with a diagnosis of chronic heart failure (NYHA Class II, III or IV).
- Patients must at least be treated with an ACE-i at a stable dose (at least enalapril 10 mg daily or any other ACE-i, e.g. ramipril, quinapril, lisinopril, fosinopril, perindopril, trandolapril; on equivalent doses, or maximum tolerated dose) or if intolerant to ACE-i with ARB therapy (Candesartan 8 mg daily or any other ARB in equivalent dose, or maximum tolerated dose) for at least 4 weeks prior to visit 1.
- Patients must be treated with a beta blocker unless contraindicated or not tolerated at a stable dose for at least 4 weeks prior to visit 1 (for patients not on target dose or in absence of that medication, the reason should be documented).
- Concomitant use of ACE-i and/or ARB and/or aldosterone antagonist is permitted.
Key exclusion criteria (36 listed)
- LVEF >45% at visit 1 (local measurement, measured within the past 12 months assessed by echocardiogram, MUGA or ventricular angiography).
- History of hypersensitivity to the study drugs.
- Patients with phenylketonuria.
- Patients with fructose intolerance.
- Current acute decompensated heart failure.
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 |
|---|---|---|
| Vitamin DAlso: Colecalciferol2000 IU vitamin D daily, for 6 weeks | Drug | Vitamin D |
Primary outcome
Plasma Renin Activity
Time frame: 6 weeks
The primary endpoint of this study is the PRA after 6 weeks of treatment with vitamin D compared to the PRA after 6 weeks without treatment.
7 secondary outcomes
Safety endpoints are biochemical indices of kidney function and bone homeostasis
Time frame: 6 weeks
To evaluate the effect of vitamin D administration on plasma values of additional markers of renin-angiotensin system activity, including angiotensin II, angiotensin converting enzyme activity and chymase activity
Time frame: 6 weeks
To evaluate the effect of vitamin D administration on different markers of the vitamin D cascade, such as vitamin D, calcium, phosphate and PTH (parathyroid hormone)
Time frame: 6 weeks
To evaluate the effect of vitamin D administration on plasma levels of NT-proBNP
Time frame: 6 weeks
To evaluate the effect of vitamin D administration on urinary levels of markers of glomerular and tubular damage
Time frame: 6 weeks
To evaluate the effect of vitamin D administration on extracellular matrix markers (PIIINP, PICP, PINP) and degradation markers (MMP1, MMP9, TIMP1, MMP1/TIMP1-complex)
Time frame: 6 weeks
To evaluate the effect of vitamin D administration on NYHA-class
Time frame: 6 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2013.
- Derived from this study: PubMed 23895820Schroten NF, Ruifrok WP, Kleijn L, Dokter MM, Sillje HH, Lambers Heerspink HJ, Bakker SJ, Kema IP, van Gilst WH, van Veldhuisen DJ, Hillege HL, de Boer RA. Short-term vitamin D3 supplementation lowers plasma renin activity in patients with stable chronic heart failure: an open-label, blinded end point, randomized prospective trial (VitD-CHF trial). Am Heart J. 2013 Aug;166(2):357-364.e2. doi: 10.1016/j.ahj.2013.05.009. Epub 2013 Jun 24.
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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.
W. T. Ruifrok, MD principal investigator
University Medical Center Groningen
R. A. de Boer, MD, PhD study director
University Medical Center Groningen
W. H. van Gilst, PhD study chair
University Medical Center Groningen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Vitamin D in people with Chronic Heart Failure, run by University Medical Center Groningen at 1 site in Netherlands.
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 5 inclusion and 36 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: finished, as of the sponsor's last update on 15 Feb 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 Netherlands. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Plasma Renin Activity (time frame: 6 weeks). 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 NCT01092130, which also lists 1 linked publication.
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 15 Feb 2013.