Renal TransplantPhase 2APPLENCT01220050
Paricalcitol in Reducing Parathyroid Hormone Levels and Ameliorating Markers of Bone Remodelling in Renal Transplant Recipients With Secondary Hyperparathyroidism
A Phase 2 study testing Paricalcitol and Standard therapy in people with Renal Transplant and Secondary Hyperparathyroidism, run by Mario Negri Institute for Pharmacological Research at 1 site in Italy.
Trial summary
The risk of fracture for kidney transplant recipients is 4 times higher that of the general population. The hyperparathyroidism plays a key role in the maintenance or development of post-transplant alterations of bone remodelling. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Renal Transplant, Secondary Hyperparathyroidism
- What is being tested?
- Paricalcitol and Standard therapy
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 1 siteItaly
- Study dates
- Sep 2009to Feb 2013
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males and females >18 years old
- Renal transplant recipients with persistent secondary hyperparathyroidism
- PTH persistently >80 pg/mL up 2 month post transplant (stable or progressively increasing PTH levels)
- No ongoing therapy with Vitamin D
- Patients on maintenance therapy with calcineurin inhibitors and Mycophenolate Mofetil or Azathioprine
- Serum creatinine < 2mg/dL
- Patients legally able to give written informed consent to the trial (signed and dated by the patient)
- Written informed consent.
Who cannot join
- Concomitant administration of other forms of Vitamin D (different from paricalcitol)
- PTH< 80 pg/ml
- Serum Ca> 10,2 mg/dL
- Clinically serious condition
- History of malignancy
- Evidence of active hepatitis C virus, hepatitis B virus or human acquired immunodeficiency virus infection
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- Specific contraindications or history of hypersensitivity to the study drugs;
- Previous history of allergy or intolerance, or evidence of immunologically-mediated renal disease, systemic diseases, cancer
- Drug or alcohol abuse
- Any chronic clinical conditions that may affect completion of the trial or confound data interpretation
- Pregnancy or lactating
- Women of childbearing potential without following a scientifically accepted form of contraception
- Legal incapacity
- Evidence of an uncooperative attitude
- Any evidence that patient will not be able to complete the trial follow-up.
- Previous diagnosis of: intellectual disability/mental retardation, dementia, schizophrenia.
Trial locations and contacts
1 site in 1 country.
Italy1 site
Mario Negri Institute - Clinical Research Center for Rare Diseases
Ranica, Bergamo, 24020
About this study
Official title: A PROSPECTIVE, PILOT, CROSS-OVER STUDY TO ASSESS THE EFFICACY OF PARICALCITOL IN REDUCING PARATHYROID HORMONE LEVELS AND AMELIORATING MARKERS OF BONE REMODELLING IN RENAL TRANSPLANT RECIPIENTS WITH SECONDARY HYPERPARATHYROIDISM
The risk of fracture for kidney transplant recipients is 4 times higher that of the general population. The hyperparathyroidism plays a key role in the maintenance or development of post-transplant alterations of bone remodelling.
Renal transplant patients are at high risk of hyperparathyroidism, largely because of long-lasting renal insufficiency before transplant, and of progressive deterioration of kidney function because of chronic allograft nephropathy (a disease of proteinuria and progressive decline of the glomerular filtration rate).In hemodialysis patients, intravenous paricalcitol (19-nor-1,25-dihydroxyvitamin D2), a new vitamin D analogue, achieves a faster and more effective normalization of parathyroid hormone (PTH) levels than calcitriol (1,25-dihydroxyvitamin D3), an effect that is associated with smaller changes in serum calcium and phosphorus levels.
Whether oral paricalcitol may help achieving a prompt reduction in serum PTH levels and, secondarily, in urinary protein excretion in renal transplant recipients with secondary hyperparathyroidism is worth investigating.
Read the detailed description
BACKGROUND The risk of fracture for kidney transplant recipients is 4 times higher that of the general population. The pathogenesis of post-transplant bone disease is multifactorial, but hyperparathyroidism plays a key role in the maintenance or development of post-transplant alterations of bone remodelling. Vitamin D and its analogues are key components of treatment aimed to prevent or ameliorate secondary hyperparathyroidism in patients with chronic kidney disease (CKD). In hemodialysis patients, intravenous paricalcitol (19-nor-1,25-dihydroxyvitamin D2), a new vitamin D analogue, achieves a faster and more effective normalization of parathyroid hormone (PTH) levels than calcitriol (1,25-dihydroxyvitamin D3), an effect that is associated with smaller changes in serum calcium and phosphorus levels. Preliminary evidence is also available that in pre-dialysis patients with CKD and secondary hyperparathyroidism, treatment with oral paricalcitol may also reduce urinary protein excretion, an effect that is independent of concomitant treatment with agents that block the renin-angiotensin system and that in the long-term might translate into slower progression to end stage kidney disease and need for renal replacement therapy.
Renal transplant patients are at high risk of hyperparathyroidism, largely because of long-lasting renal insufficiency before transplant, and of progressive deterioration of kidney function because of chronic allograft nephropathy (a disease of proteinuria and progressive decline of the glomerular filtration rate). Whether oral paricalcitol may help achieving a prompt reduction in serum PTH levels and, secondarily, in urinary protein excretion in renal transplant recipients with secondary hyperparathyroidism is worth investigating.
AIMS Primary To evaluate whether 6-months treatment with paricalcitol may achieve a prompt and effective reduction in PTH serum levels in stable renal transplant patients with secondary hyperparathyroidism.
DESIGN This will be a Prospective, Randomized, Open label, Cross-over study of 6-months with Paricalcitol or standard treatment for hyperparathyroidism.
After one month wash-out from any form of Vitamin D therapy, patients satisfying the inclusion/exclusion criteria will be randomized to two treatment arms:
- Paricalcitol capsules 1- 2 mcg/day/pts for 26 weeks
- Standard therapy for hyperparathyroidism for 26 weeks At the end of the first treatment period with Paricalcitol or Standard therapy each patient will cross-over to the other treatment.
After baseline evaluation eligible patients will enter a 6 months treatment period whit oral paricalcitol (1-2 mcg/day), or standard treatment for hyperparathyroidism, added-on background therapy whit calcium and phosphate supplementation as deemed clinically appropriate.
- Conditions
- Renal Transplant, Secondary Hyperparathyroidism
- Being tested
- Paricalcitol, Standard therapy
- Keywords
- Paricalcitol, Renal transplant, Secondary Hyperparathyroidism
- Medical subject headings
- Hyperparathyroidism, Secondary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ParicalcitolDrug
Paricalcitol capsules 1- 2 mcg/day/pts for 26 weeks
Standard therapyDrug
Standard therapy for hyperparathyroidism for 26 weeks
| Study group | Role | What they receive |
|---|---|---|
| Paricalcitol | Experimental | Not described Receives: Drug: Paricalcitol |
| Standard therapy | Active comparator | Not described Receives: Drug: Standard therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
PTH reduction during the 6 months of paricalcitol therapy (during both treatment periods) compared to the change in PTH levels during the corresponding 6 months without paricalcitol therapy.
Measured: Every three months.
Secondary outcomes (4)
Measurement of osteocalcin.
Measured: Baseline and then every three months.
Measurement of bone alkaline phosphatase.
Measured: Baseline and then every three months.
Measurement of urinary deoxypyridinoline.
Measured: Baseline and then every three months.
Bone mineral density (by MOC).
Measured: At baseline and at the end of both treatment periods.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2010 (estimated)
- Study startSep 2009
- Primary completionJul 2012
- Study completionFeb 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Renal TransplantStudies of the same condition, open and under way.
- More trials run by Mario Negri Institute for Pharmacological ResearchThe 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
- Crossover
- Masking
- None (open label)
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01220050
- Sponsor's protocol ID
- APPLE
- Other IDs
- 2008-006380-36, 2008
- Acronym
- APPLE
- Status last verified
- Feb 2013
- First submitted
- 11 Oct 2010
- Last updated
- 22 Feb 2013
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A PROSPECTIVE, PILOT, CROSS-OVER STUDY TO ASSESS THE EFFICACY OF PARICALCITOL IN REDUCING PARATHYROID HORMONE LEVELS AND AMELIORATING MARKERS OF BONE REMODELLING IN RENAL TRANSPLANT RECIPIENTS WITH SECONDARY HYPERPARATHYROIDISM
- ClinicalTrials.gov ID
- NCT01220050
- Acronym / sponsor ID
- APPLE / APPLE
- Conditions
- Renal Transplant, Secondary Hyperparathyroidism
- Keywords
- Paricalcitol, Renal transplant, Secondary Hyperparathyroidism
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- Mario Negri Institute for Pharmacological ResearchUniversity, hospital or other
- Study start
- Sep 2009
- Primary completion
- Jul 2012 (actual)
- Study completion
- Feb 2013 (actual)
- First posted
- 13 Oct 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 risk of fracture for kidney transplant recipients is 4 times higher that of the general population. The hyperparathyroidism plays a key role in the maintenance or development of post-transplant alterations of bone remodelling.
Renal transplant patients are at high risk of hyperparathyroidism, largely because of long-lasting renal insufficiency before transplant, and of progressive deterioration of kidney function because of chronic allograft nephropathy (a disease of proteinuria and progressive decline of the glomerular filtration rate).In hemodialysis patients, intravenous paricalcitol (19-nor-1,25-dihydroxyvitamin D2), a new vitamin D analogue, achieves a faster and more effective normalization of parathyroid hormone (PTH) levels than calcitriol (1,25-dihydroxyvitamin D3), an effect that is associated with smaller changes in serum calcium and phosphorus levels.
Whether oral paricalcitol may help achieving a prompt reduction in serum PTH levels and, secondarily, in urinary protein excretion in renal transplant recipients with secondary hyperparathyroidism is worth investigating.
Detailed description
BACKGROUND The risk of fracture for kidney transplant recipients is 4 times higher that of the general population. The pathogenesis of post-transplant bone disease is multifactorial, but hyperparathyroidism plays a key role in the maintenance or development of post-transplant alterations of bone remodelling. Vitamin D and its analogues are key components of treatment aimed to prevent or ameliorate secondary hyperparathyroidism in patients with chronic kidney disease (CKD). In hemodialysis patients, intravenous paricalcitol (19-nor-1,25-dihydroxyvitamin D2), a new vitamin D analogue, achieves a faster and more effective normalization of parathyroid hormone (PTH) levels than calcitriol (1,25-dihydroxyvitamin D3), an effect that is associated with smaller changes in serum calcium and phosphorus levels. Preliminary evidence is also available that in pre-dialysis patients with CKD and secondary hyperparathyroidism, treatment with oral paricalcitol may also reduce urinary protein excretion, an effect that is independent of concomitant treatment with agents that block the renin-angiotensin system and that in the long-term might translate into slower progression to end stage kidney disease and need for renal replacement therapy.
Renal transplant patients are at high risk of hyperparathyroidism, largely because of long-lasting renal insufficiency before transplant, and of progressive deterioration of kidney function because of chronic allograft nephropathy (a disease of proteinuria and progressive decline of the glomerular filtration rate). Whether oral paricalcitol may help achieving a prompt reduction in serum PTH levels and, secondarily, in urinary protein excretion in renal transplant recipients with secondary hyperparathyroidism is worth investigating.
AIMS Primary To evaluate whether 6-months treatment with paricalcitol may achieve a prompt and effective reduction in PTH serum levels in stable renal transplant patients with secondary hyperparathyroidism.
DESIGN This will be a Prospective, Randomized, Open label, Cross-over study of 6-months with Paricalcitol or standard treatment for hyperparathyroidism.
After one month wash-out from any form of Vitamin D therapy, patients satisfying the inclusion/exclusion criteria will be randomized to two treatment arms:
- Paricalcitol capsules 1- 2 mcg/day/pts for 26 weeks
- Standard therapy for hyperparathyroidism for 26 weeks At the end of the first treatment period with Paricalcitol or Standard therapy each patient will cross-over to the other treatment.
After baseline evaluation eligible patients will enter a 6 months treatment period whit oral paricalcitol (1-2 mcg/day), or standard treatment for hyperparathyroidism, added-on background therapy whit calcium and phosphate supplementation as deemed clinically appropriate.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Paricalcitol | Experimental | Drug: Paricalcitol |
| Standard therapy | Active comparator | Drug: Standard therapy |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Males and females >18 years old
- Renal transplant recipients with persistent secondary hyperparathyroidism
- PTH persistently >80 pg/mL up 2 month post transplant (stable or progressively increasing PTH levels)
- No ongoing therapy with Vitamin D
- Patients on maintenance therapy with calcineurin inhibitors and Mycophenolate Mofetil or Azathioprine
Key exclusion criteria (16 listed)
- Concomitant administration of other forms of Vitamin D (different from paricalcitol)
- PTH< 80 pg/ml
- Serum Ca> 10,2 mg/dL
- Clinically serious condition
- History of malignancy
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 |
|---|---|---|
| ParicalcitolParicalcitol capsules 1- 2 mcg/day/pts for 26 weeks | Drug | Paricalcitol |
| Standard therapyStandard therapy for hyperparathyroidism for 26 weeks | Drug | Standard therapy |
Primary outcome
PTH reduction during the 6 months of paricalcitol therapy (during both treatment periods) compared to the change in PTH levels during the corresponding 6 months without paricalcitol therapy.
Time frame: Every three months.
4 secondary outcomes
Measurement of osteocalcin.
Time frame: Baseline and then every three months.
Measurement of bone alkaline phosphatase.
Time frame: Baseline and then every three months.
Measurement of urinary deoxypyridinoline.
Time frame: Baseline and then every three months.
Bone mineral density (by MOC).
Time frame: At baseline and at the end of both treatment periods.
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 22 Feb 2013.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Paricalcitol and Standard therapy in people with Renal Transplant and Secondary Hyperparathyroidism, run by Mario Negri Institute for Pharmacological Research at 1 site in Italy.
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 8 inclusion and 16 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 22 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 Italy. 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?
PTH reduction during the 6 months of paricalcitol therapy (during both treatment periods) compared to the change in PTH levels during the corresponding 6 months without paricalcitol therapy. (time frame: Every three months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 22 Feb 2013.