Vascular CalcificationPhase 4NCT00395382
Study of the Effect of Alendronate on Vascular Calcification and Arterial Stiffness in Chronic Kidney Disease
A Phase 4 study testing Alendronate in people with Vascular Calcification and Arteriosclerosis, run by Monash University at 1 site in Australia.
Trial summary
Cardiovascular disease (CVD) is the commonest cause of mortality in patients with chronic kidney disease (CKD) and end-stage kidney disease (ESKD). Reasons for the greater incidence of CVD in this group include traditional CVD risk factors of hypertension, dyslipidemia and diabetes but more importantly also include… Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Vascular Calcification, Arteriosclerosis
- What is being tested?
- Alendronate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteAustralia
- Study dates
- Jan 2007to Sep 2009
- Phase
- Phase 4
- 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 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects with CKD Stage 3 (GFR between 30 and 59ml/min)
- Subjects must be 18 years of age or older
- Willingness to provide written informed consent
Who cannot join
- Subjects unable to give informed consent or whom have an expected life-span of less than 3 months
- Subjects undertaking renal replacement therapy (dialysis or transplantation)
- Subjects already taking bisphosphonates
- Subjects with recent fracture (within the last 3 months)
- Subjects scheduled to have a kidney transplant from a known living donor
- Subjects with active gastro-oesophageal reflux disease or peptic ulcer disease
- Subjects who are pregnant or planning on becoming pregnant in the next 18 months
Trial locations and contacts
1 site in 1 country.
Australia1 site
Department of Nephrology, Monash Medical Centre
Clayton, Victoria, 3168
About this study
Official title: Randomised Controlled Trial of the Effect of Alendronate on Vascular Calcification and Arterial Stiffness in Chronic Kidney Disease: A Pilot Study
Cardiovascular disease (CVD) is the commonest cause of mortality in patients with chronic kidney disease (CKD) and end-stage kidney disease (ESKD). Reasons for the greater incidence of CVD in this group include traditional CVD risk factors of hypertension, dyslipidemia and diabetes but more importantly also include non-traditional risk factors such as calcium and phosphate imbalance. The latter is thought most likely to contribute to vascular calcification, especially for those on dialysis, and this in turn leads to arterial stiffness and left ventricular hypertrophy, the two commonest cardiovascular complications. Arterial stiffness and calcification have been found to be independent predictors of all-cause and cardiovascular mortality in CKD. Few studies, though, have looked at both structural and functional changes associated with calcification and there have been very few interventional studies addressing this issue.
Control of calcium and phosphate levels in CKD can occur with the use of medications that reduce elevated serum phosphate (phosphate binders, mostly calcium-based) and those to treat hyperparathyroidism (vitamin D and more recently calcium sensing receptor agonists called calcimimetics). These pharmacological managements addressing calcium and phosphate imbalance reduce vascular calcification and CVD. Bisphosphonate therapy may also have a role in reduction of calcification.
Read more
Low bone mineral density (BMD) is common in CKD patients and predicts increased fracture risk similar to the general population. Bisphosphonate therapy improves BMD and lowers the fracture risk. Bisphosphonates may also have a role in secondary hyperparathyroidism to reduce hypercalcemia and allow for more aggressive calcitriol treatment. Recent studies have addressed the possibility of bisphosphonates reducing the progression of vascular calcification in CKD and revealed that the extent of calcification may be suppressed in association with a reduction in chronic inflammatory responses.
The investigators aim to perform a prospective, randomised study assessing the impact of alendronate on cardiovascular and bone mineral parameters. This will be a single-centre study involving subjects with CKD Stage 3 (those patients with GFR between 30 and 59ml/min). Arterial stiffness (by pulse wave analysis and pulse wave velocity) and vascular calcification (using CT scans through superficial femoral artery) will be followed as well as serum markers of calcium, phosphate and PTH. Differences in these end-points will be compared between participants taking alendronate and those not. The study will be conducted over a 12 month period and the investigators aim to recruit about 50 patients (25 on alendronate and 25 control).
- Conditions
- Vascular Calcification, Arteriosclerosis
- Being tested
- Alendronate, Placebo
- Keywords
- Vascular calcification, Arterial stiffness, Cardiovascular risk, Bone mineral metabolism, Calcium
- Medical subject headings
- Vascular Calcification, Arteriosclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlendronateDrug
Also called Fosamax
70mg weekly orally
PlaceboDrug
weekly orally
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Alendronate Receives: Drug: Alendronate |
| 2 | Placebo comparator | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in degree of arterial stiffness measured by pulse wave velocity
Measured: 18 months
Changes in vascular calcification on CT scans of superficial femoral artery and aorta
Measured: 18 months
Secondary outcomes (6)
Changes in bone mineral density
Measured: 18 months
Changes in serum calcium and phosphate levels
Measured: 18 months
Cardiovascular events including myocardial ischaemia, myocardial infarction, cardiac failure, stroke, PVD
Measured: 18 months
Incidence of fractures
Measured: 18 months
Symptoms and severity of side effects from alendronate
Measured: 18 months
Episodes of hypocalcemia (serum corrected calcium <2.10mmol/L)
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Nov 2006 (estimated)
- Study startJan 2007
- Primary completionSep 2009
- Study completionSep 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Vascular CalcificationStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Monash University
- Sponsor type
- University, hospital or other
- Investigators
- Peter G Kerr, MBBS FRACP, Principal investigator, Monash Medical Centre, Clayton, Victoria, Australia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00395382
- Sponsor's protocol ID
- HREC 06099C
- Status last verified
- Feb 2010
- First submitted
- 1 Nov 2006
- Last updated
- 9 Feb 2010
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Hara T, Hijikata Y, Matsubara Y, Watanabe N. Pharmacological interventions versus placebo, no treatment or usual care for osteoporosis in people with chronic kidney disease stages 3-5D. Cochrane Database Syst Rev. 2021 Jul 7;7(7):CD013424. doi: 10.1002/14651858.CD013424.pub2.
PubMed 34231877Toussaint ND, Lau KK, Strauss BJ, Polkinghorne KR, Kerr PG. Using vertebral bone densitometry to determine aortic calcification in patients with chronic kidney disease. Nephrology (Carlton). 2010 Aug;15(5):575-83. doi: 10.1111/j.1440-1797.2010.01288.x.
PubMed 20649879
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomised Controlled Trial of the Effect of Alendronate on Vascular Calcification and Arterial Stiffness in Chronic Kidney Disease: A Pilot Study
- ClinicalTrials.gov ID
- NCT00395382
- Acronym / sponsor ID
- HREC 06099C
- Conditions
- Vascular Calcification, Arteriosclerosis
- Keywords
- Vascular calcification, Arterial stiffness, Cardiovascular risk, Bone mineral metabolism, Calcium
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Monash UniversityUniversity, hospital or other
- Study start
- Jan 2007
- Primary completion
- Sep 2009 (actual)
- Study completion
- Sep 2009 (actual)
- First posted
- 2 Nov 2006 (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.
Cardiovascular disease (CVD) is the commonest cause of mortality in patients with chronic kidney disease (CKD) and end-stage kidney disease (ESKD). Reasons for the greater incidence of CVD in this group include traditional CVD risk factors of hypertension, dyslipidemia and diabetes but more importantly also include non-traditional risk factors such as calcium and phosphate imbalance. The latter is thought most likely to contribute to vascular calcification, especially for those on dialysis, and this in turn leads to arterial stiffness and left ventricular hypertrophy, the two commonest cardiovascular complications. Arterial stiffness and calcification have been found to be independent predictors of all-cause and cardiovascular mortality in CKD. Few studies, though, have looked at both structural and functional changes associated with calcification and there have been very few interventional studies addressing this issue.
Control of calcium and phosphate levels in CKD can occur with the use of medications that reduce elevated serum phosphate (phosphate binders, mostly calcium-based) and those to treat hyperparathyroidism (vitamin D and more recently calcium sensing receptor agonists called calcimimetics). These pharmacological managements addressing calcium and phosphate imbalance reduce vascular calcification and CVD. Bisphosphonate therapy may also have a role in reduction of calcification.
Low bone mineral density (BMD) is common in CKD patients and predicts increased fracture risk similar to the general population. Bisphosphonate therapy improves BMD and lowers the fracture risk. Bisphosphonates may also have a role in secondary hyperparathyroidism to reduce hypercalcemia and allow for more aggressive calcitriol treatment. Recent studies have addressed the possibility of bisphosphonates reducing the progression of vascular calcification in CKD and revealed that the extent of calcification may be suppressed in association with a reduction in chronic inflammatory responses.
The investigators aim to perform a prospective, randomised study assessing the impact of alendronate on cardiovascular and bone mineral parameters. This will be a single-centre study involving subjects with CKD Stage 3 (those patients with GFR between 30 and 59ml/min). Arterial stiffness (by pulse wave analysis and pulse wave velocity) and vascular calcification (using CT scans through superficial femoral artery) will be followed as well as serum markers of calcium, phosphate and PTH. Differences in these end-points will be compared between participants taking alendronate and those not. The study will be conducted over a 12 month period and the investigators aim to recruit about 50 patients (25 on alendronate and 25 control).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: AlendronateAlendronate |
| 2 | Placebo comparator | Drug: PlaceboPlacebo |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Subjects with CKD Stage 3 (GFR between 30 and 59ml/min)
- Subjects must be 18 years of age or older
- Willingness to provide written informed consent
Key exclusion criteria (7 listed)
- Subjects unable to give informed consent or whom have an expected life-span of less than 3 months
- Subjects undertaking renal replacement therapy (dialysis or transplantation)
- Subjects already taking bisphosphonates
- Subjects with recent fracture (within the last 3 months)
- Subjects scheduled to have a kidney transplant from a known living donor
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 |
|---|---|---|
| AlendronateAlso: Fosamax70mg weekly orally | Drug | 1 |
| Placeboweekly orally | Drug | 2 |
Primary outcome
Change in degree of arterial stiffness measured by pulse wave velocity
Time frame: 18 months
Changes in vascular calcification on CT scans of superficial femoral artery and aorta
Time frame: 18 months
6 secondary outcomes
Changes in bone mineral density
Time frame: 18 months
Changes in serum calcium and phosphate levels
Time frame: 18 months
Cardiovascular events including myocardial ischaemia, myocardial infarction, cardiac failure, stroke, PVD
Time frame: 18 months
Incidence of fractures
Time frame: 18 months
Symptoms and severity of side effects from alendronate
Time frame: 18 months
Episodes of hypocalcemia (serum corrected calcium <2.10mmol/L)
Time frame: 18 months
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 9 Feb 2010.
- Derived from this study: PubMed 34231877Hara T, Hijikata Y, Matsubara Y, Watanabe N. Pharmacological interventions versus placebo, no treatment or usual care for osteoporosis in people with chronic kidney disease stages 3-5D. Cochrane Database Syst Rev. 2021 Jul 7;7(7):CD013424. doi: 10.1002/14651858.CD013424.pub2.
- Derived from this study: PubMed 20649879Toussaint ND, Lau KK, Strauss BJ, Polkinghorne KR, Kerr PG. Using vertebral bone densitometry to determine aortic calcification in patients with chronic kidney disease. Nephrology (Carlton). 2010 Aug;15(5):575-83. doi: 10.1111/j.1440-1797.2010.01288.x.
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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.
Peter G Kerr, MBBS FRACP principal investigator
Monash Medical Centre, Clayton, Victoria, Australia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Alendronate in people with Vascular Calcification and Arteriosclerosis, run by Monash University at 1 site in Australia.
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 3 inclusion and 7 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 9 Feb 2010. 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 Australia. 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. Some participants in this study may receive a placebo. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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?
Change in degree of arterial stiffness measured by pulse wave velocity (time frame: 18 months). The study lists 2 primary outcomes in all. 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 NCT00395382, which also lists 2 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 9 Feb 2010.