Clinical trial NCT01166178: Zoledronic Acid in MS-patients With Osteoporosis
Official title: A 1-year, Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel Group Study to Evaluate the Efficacy of Zoledronic Acid 5 mg (Aclasta®) on Bone Mineral Density in Patients With Multiple Sclerosis Followed by a 1-year Open-label Treatment Phase
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Osteoporosis
Multiple Sclerosis
Keywords: Multiple Sclerosis
Osteoporosis
Zoledronic Acid
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2010-07-20
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is designed to evaluate the efficacy and safety of zoledronic acid 5 mg intravenous (i.v.) relative to placebo in Multiple Sclerosis (MS) patients with osteoporosis and to support the optimal use of zoledronic acid for this indication. Primary objective is the change of Bone Mineral Density (BMD) at lumbar spine (L1-L4) and total hip region assessed by T-Score at month 12 relative to screening as measured by Dual X-ray Absorptiometry (DXA). This double-blind period will be followed by a 52-week open-label treatment phase to assess long-term efficacy and safety of zoledronic acid in these patients.


Eligibility criteria: Inclusion:

* Written informed consent to participate in the trial
* Definite diagnosis of Multiple Sclerosis (MS) as defined by 2005 revised McDonald criteria
* MS-subtype: Relapsing-remitting MS (RRMS), Secondary progressive MS (SPMS), Primary progressive MS (PPMS)
* Expanded Disability Status Scale (Kurtzke's scale; EDSS) score between 2.5 to 6.5 (including both)
* Bone mineral density (BMD) T-score of less or equal to -2.0 and more or equal to -4.0 at the lumbar spine (L1-L4 with at least 2 evaluable vertebrae) and/or total hip region and/or femoral neck in recent Dual X-Ray Absorptiometry (DXA)-scan (\< or = 3 months)
* Sufficient ability to read, write and communicate comprehensibly and comply to study procedures
* No immunomodulatory treatment for MS within the last 30 days or stable and well tolerated therapy with any beta-interferon formulation, or glatirameracetate or fingolimod for at least 30 days immediately prior to baseline

Exclusion criteria:

* Contraindications against Calcium and Vitamin D and zoledronic acid according to the summary product characteristics
* More than one osteoporotic fracture
* Concomitant medication with influence on bone mineral density (eg. enzyme- inducing antiepileptics like Carbamazepin, Phenytoin, Phenobarbital, Primidon)
* Any neurological disorder other than MS which is known to affect bone mineral density (e.g. muscular dystrophy, severe paresis for other reasons than MS, degenerative nervous disorder, stroke)
* Women who are pregnant or breast feeding, or menstruating and capable of becoming pregnant.
* Baseline renal insufficiency
* 25-OH vitamin D level \< 10 ng/ml at screening
* Serum calcium levels \> 2.75 mmol/l (11.0 mg/dL) or \< 2.00 mmol/L (8.0 mg/dL) at screening
* Other protocol-defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: Change in Bone Mineral Density of the Lumbar Spine at 12 Months
timeFrame: Screening (day -21 to -1) and month 12
measure: Change in Bone Mineral Density of the Total Hip Region at 12 Months
timeFrame: Screening (day -21 to -1) and month 12
Secondary outcomes:
measure: Change in Bone Mineral Density of the Lumbar Spine at 6 Months
timeFrame: Screening (day -21 to -1) and month 6
measure: Change in Bone Mineral Density of the Femoral Neck at 6 Months
timeFrame: Screening (day -21 to -1) and month 6
measure: Change in Bone Mineral Density of the Total Hip at 6 Months
timeFrame: Screening (day -21 to -1) and month 6
measure: Change in Bone Mineral Density of the Femoral Neck at 12 Months
timeFrame: Screening (day -21 to -1) and month 12
measure: Change in Bone Mineral Density of the Lumbar Spine at 24 Months
timeFrame: Screening (day -21 to -1) and month 24
measure: Change in Bone Mineral Density of the Total Hip Region at 24 Months
timeFrame: Screening (day -21 to -1) and month 24
measure: Change in Bone Mineral Density of the Femoral Neck at 24 Months
timeFrame: Screening (day -21 to -1) and month 24
measure: Course of Disease in Multiple Sclerosis Patients
timeFrame: Screening (day -21 to -1) and month 12
measure: Adverse Events and Serious Adverse Events Comparison of Treatment Groups
timeFrame: 24 months
Other outcomes:
Locations:
city: Bamberg
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Bochum
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Heidelberg
country: Germany
facility: Novartis Investigative Site
city: Kassel
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis investigative site
city: Leverkusen
country: Germany
facility: Novartis Investigative Site
city: Ludwigshafen
country: Germany
facility: Novartis investigative site
city: Magdeburg
country: Germany
facility: Novartis investigative site
city: Muenchen
country: Germany
facility: Novartis investigative site
city: Numbrecht
country: Germany
facility: Novartis investigative site
city: Oldenburg
country: Germany
facility: Novartis investigative site
city: Siegen
country: Germany
facility: Novartis Investigative Site
city: Stade
country: Germany
facility: Novartis investigative site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmceuticals
role: STUDY_DIRECTOR
References: