Zoledronic Acid in MS-patients With Osteoporosis
Condition: Osteoporosis; Multiple Sclerosis
MeSH terms: Osteoporosis; Multiple Sclerosis; Sclerosis
Intervention: Zoledronic Acid; Placebo; Calcium and Vitamin D combination
Intervention description: Zoledronic acid 5 mg once a year via intravenous infusion; Placebo to zoledronic acid once a year via intravenous infusion; Calcium 500 mg and Vitamin D 400 IU combined tablet, taken orally twice a day
Intervention MeSH terms: Vitamin D; Zoledronic Acid; Calcium
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 29.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Multiple Sclerosis; Osteoporosis; Zoledronic Acid

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