Ibandronate Versus Placebo in the Prevention of Bone Loss After Renal Transplantation.

Ibandronate Versus Placebo as add-on to Active Vitamin D and Calcium in the Prevention of Bone Loss After Renal Transplantation.

Loss of bone mass is a common complication in patients with end-stage-renal failure, both before and particularly after transplantation. In addition to standard underlying therapy with calcium and active vitamin D, we will study the effect of ibandronate (a bisphosphonate) versus placebo on bone mineral density as well as incidence of fracture rates after kidney transplantation.We also wish to study whether any prevented bone loss will also lead to reduced cardiovascular disease. Patients will be followed for 12 months after transplantation, and the ibandronate treatment is one injection every 3 months.

Study Overview

• Status: Unknown
• Conditions: Renal Transplant
• Intervention / Treatment: Drug: Placebo; Drug: Ibandronate

Detailed Description

Demographic, medical history, previous and current medication, as well as baseline measurements of Bone Mineral Density (BMD), laboratory efficacy and safety variables as well as Quality-of-Life scores will be undertaken in the period from 1 week prior to transplantation until 1 week after transplantation. In this period, any existing fractures will be determined using traditional x-ray of the thoraco-lumbar columna. Renal graft functioning as well as transplantation complications will be followed tightly, and calcium supplementation as well as active vitamin D (calcitriol) will be administered together with the standard immunosuppressive regimen.

As soon as patients have recovered from transplantation, and renal functioning is considered sufficiently stable, and no later than 28 days after the transplantation, qualified patients will be randomised to receive either ibandronate or placebo, stratified by gender. Bone mineral density and most of the clinical data and laboratory tests will then be followed until 12 months after transplantation as described in the attached flowchart (section 11.1), with hospital visits for administration of study drugs and follow-up of at 13, 26, 39 and 52 weeks after transplantation. Furthermore, all the patients will be followed prospectively from the time of transplantation and for ten years with regard to cardiovascular events. Data concerning cardiovascular events will be collected from the Norwegian renal registry for the whole study population in the follow up period of about 10 years.

• Study Type: Interventional
• Enrollment (Anticipated): 130
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Norway
  • Oslo, Norway, 0027
    • Rikshospitalet-Radiumhospitalet Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Renal transplant recipients
• Adults, ≥ 18 years of age
• Either gender
• Signed informed consent

Exclusion Criteria:

• Persisting s-Ca > 2.55 mmol/L (through the first two weeks after transplantation)
• Impaired graft functioning (estimated GFR <30 ml/min)
• Previous (within the last 12 months) treatment with bisphosphonates, sodium fluoride, calcitonin, strontium, PTH, SERM, growth hormone or anabolic steroids at any time before transplantation.
• Known adynamic bone disease
• Previous parathyroidectomy
• Pregnant or lactating females or females of childbearing potential who do not use an approved method of contraception (oral contraceptives or IUD); positive urine pregnancy test, where applicable.
• Use of any investigational drug (s) and/or device(s)
• Previous participation in this trial
• History of hypersensitivity to bisphosphonates

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 2	Drug: Placebo; Placebo
Experimental: 1; Ibandronate	Drug: Ibandronate; I.v.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Difference in percent lumbar BMD change from baseline to 12 months between the two treatment groups.	December 2010

Secondary Outcome Measures

Outcome Measure	Time Frame
Lumbar BMD change; absolute and relative	December 2010
Hip BMD change; absolute and relative	December 2010
Radial BMD change; absolute and relative	December 2010
Femural BMD change; absolute and relative	December 2010
Change in height	December 2010
Change in biochemical efficacy and bone markers	December 2010
Change in HRQoL scores (SF-36 and mini OQOL)	December 2010
Incidence of post-transplant complications	December 2010
Frequency of clinically significant safety laboratory variables	December 2010
Adverse event rates	December 2010

Collaborators and Investigators

• Sponsor: Smerud Medical Research International AS
• Collaborators: Oslo University Hospital

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Anticipated): December 1, 2009
• Study Completion (Anticipated): December 1, 2010

Study Registration Dates

• First Submitted: January 17, 2007
• First Submitted That Met QC Criteria: January 17, 2007
• First Posted (Estimate): January 18, 2007

Study Record Updates

• Last Update Posted (Estimate): March 24, 2010
• Last Update Submitted That Met QC Criteria: March 22, 2010
• Last Verified: March 1, 2010

More Information

Terms related to this study

• Keywords: transplant; Bone; Kidney; Placebo; loss; Ibandronate; Doubleblind
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Bone Density Conservation Agents; Ibandronic Acid
• Other Study ID Numbers: SMR-1471; EUDRACT no.: 2006-003884-30