Clinical trial NCT00587158: Oral Paricalcitol in Kidney Transplant Recipients
Official title: Oral Paricalcitol in Kidney Transplant Recipients Receiving a Corticosteroid-free Immunosuppressive Regimen
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Transplant; Failure, Kidney
Renal Disease, End Stage
Hyperparathyroidism, Secondary
Keywords: Paricalcitol
Parathyroid Hormone
Bone Alkaline Phosphatase
Chronic Kidney Disease
Glomerular Filtration Rate
Vitamin D Receptor
Interstitial Fibrosis and Tubular Atrophy
Zemplar®
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: Abbott
First posted: 2008-01-07
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is being done to find out whether patients who receive a kidney transplant can benefit from taking the medication paricalcitol (trade name Zemplar®) as compared to kidney transplant recipients not taking this medication. The main possible benefits being studied are:

* Lower risk for overactive parathyroid glands after kidney transplantation.
* Lower risk of low bone density in the spine and hip after kidney transplantation. By dividing patients in the study into a group receiving Zemplar® and a group not receiving Zemplar®, it will be possible to understand the good and bad effects of Zemplar® during the first year after a kidney transplant.

Detailed description: The most significant challenge in kidney transplantation at present is that of reducing the risk of long-term complications. This includes hyperparathyroidism, a common post kidney transplant complication that contributes to loss of bone density and fracture risk and necessitates surgical intervention in approximately 5% of kidney transplant patients.

In order to take part in the study you will already have been accepted for kidney transplantation from a living donor or from a deceased donor at Mayo Clinic in Rochester, Minnesota. After you have agreed to take part in the study you will be put in one of two groups by chance (as in the flip of a coin):

Group 1 (Standard Treatment or "Control"): Patients in this group will receive a combination of four anti-rejection medications that have been used at Mayo Clinic Rochester for many kidney transplant patients and does not include any research study medicines. These medications will include:

1. Alemtuzumab (Campath®) - this medicine will be given intravenously (IV) on the day of the transplant during surgery.
2. Methylprednisolone (Solumedrol®) - this medicine, which is part of a family of medicines often referred to as corticosteroids, will be given intravenously on the day of the transplant during surgery. This will be the only planned dose of corticosteroid medicine you will receive although this medicine and a tablet form called Prednisone may be given at a later time if you have an episode of transplant rejection.
3. Mycophenolate Mofetil (Cellcept®) - this medicine will be given by mouth twice daily beginning the evening before the transplant (for living donor transplants) or the day of the transplant (for deceased donor transplants). It will be continued for as long as you have your transplant unless there is a medical reason to stop it.
4. Tacrolimus (Prograf®) - this medicine will be given by mouth once daily beginning on the fourth day after the transplant. It will continue for as long as you have your transplant unless there is a medical reason to stop it. The dose will be adjusted based on a blood test that will be done between twice a week and once a month for as long as you take the medicine.

Group 2 (Zemplar® + Standard Treatment): Patients in this group will receive the same combination of anti-rejection medications as the patients in Group 1 (a-d above) plus Zemplar®, which is the medicine being studied, will also be started on the day of the transplant. Zemplar® will be given as a capsule containing 1 microgram of Zemplar® once daily beginning the day after the transplant. It will be continued at the same dose for the first two weeks then, depending on the results of blood and urine testing, will be increased to 2 micrograms daily. The dose will remain at 2 micrograms daily until the end of the study unless there is a medical reason to reduce or stop it or unless the study is stopped early.

Both groups of patients will be treated by the same team of doctors, nurses and nurse coordinators that care for all kidney transplant patients at Mayo Clinic. The procedures and treatments for your transplant will be the same as those recommended at Mayo Clinic for all patients receiving a kidney transplant. These include the surgical operation to carry out the transplant; the need to take anti-rejection medicines by mouth for the rest of your life; the need to have blood and urine testing at regular intervals for the rest of your life to monitor the progress of your transplant; and the recommendation to have a biopsy of your transplant carried out on three occasion during the first two years after the transplant surgery. These procedures and their potential complications will be described to you in detail by your transplant physician, transplant surgeon, and transplant coordinator. The study will not require extra hospital or outpatient visits compared to the usual care for all kidney transplant patients at Mayo Clinic Rochester.

Eligibility criteria: Inclusion Criteria:

* Age 18 years and older.
* First or second deceased donor or living donor renal transplant.
* Normocalcemia or hypocalcemia.
* Willing to give informed consent

Exclusion Criteria:

* Third or subsequent renal transplant.
* Incompatible blood type or positive cross-match donor.
* Multiple organ transplant recipients.
* Diabetic with plans for future pancreas or islet transplant.
* Evidence of donor-specific sensitization (positive T-cell and/or B-cell flow cytometric cross-match).
* Documented hypercalcemia (total serum calcium 10.5 mg/dl on two separate occasions) prior to transplantation.
* Serum 25(OH)vitamin D concentration ≤ 10 ng/ml

Primary outcomes:
measure: Number of Subjects With Hyperparathyroidism at One Year
timeFrame: 1 year post kidney transplant
Secondary outcomes:
measure: Number of Subjects With Osteopenia/Osteoporosis of the Hip at One Year
timeFrame: 1 year post kidney transplant
measure: Number of Subjects With Osteopenia/Osteoporosis of the Lumbar Spine at One Year
timeFrame: 1 year post kidney transplant
measure: Serum Parathyroid Hormone (PTH) Level Over Time
timeFrame: Baseline, 3 weeks, 3 months, 1 year post kidney transplant
measure: Serum Bone Alkaline Phosphatase (BAP) Level Over Time
timeFrame: Baseline, 21 days, 90 days and 1 year post kidney transplant
measure: Change in Lumbar Spine Bone Mineral Density (BMD)
timeFrame: Baseline, 1 year post kidney transplant
measure: Change in Hip Bone Mineral Density (BMD)
timeFrame: Baseline, 1 year post kidney transplant
measure: Number of Subjects Who Died or Lost Their Renal Graft During First Year
timeFrame: Baseline to 1 year post kidney transplant
measure: Episodes of Acute Cellular Rejection (ACR) of the Renal Transplant
timeFrame: Baseline to 1 year post kidney transplant
measure: Mean Estimated Glomerular Filtration Rate (eGFR) at One Year
timeFrame: 1 year post kidney transplant
measure: Mean Change in Estimated Glomerular Filtration Rate (eGFR) Between 3 Weeks and 1 Year Post Transplant
timeFrame: 3 weeks, 1 year post kidney transplant
measure: 24-hour Total Protein in the Urine at 1 Year Post Transplant
timeFrame: 1 year post kidney transplant
measure: Degree of Interstitial Fibrosis on Graft Biopsy at One Year
timeFrame: 1 year post kidney transplant
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic
state: Arizona
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Hatem Amer, MD
role: PRINCIPAL_INVESTIGATOR
References: