Zoledronic Acid in MS-patients With Osteoporosis (EXALT)

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Novartis
ClinicalTrials.gov Identifier:
NCT01166178
First received: July 19, 2010
Last updated: October 24, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Osteoporosis
Multiple Sclerosis
Drug: Zoledronic Acid
Drug: Placebo
Dietary Supplement: Calcium and Vitamin D combination
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Change in Bone Mineral Density of the Lumbar Spine at 12 Months [ Time Frame: Screening (day -21 to -1) and month 12 ] [ Designated as safety issue: No ]

    Change in bone mineral density (BMD) of the lumbar spine was measured using Dual X-ray Absorptiometry (DXA) at screening and at month 12.

    A DXA scanner is a device that uses x-ray beams to measure the amount of minerals in the bone.


  • Change in Bone Mineral Density of the Total Hip Region at 12 Months [ Time Frame: Screening (day -21 to -1) and month 12 ] [ Designated as safety issue: No ]

    Change in bone mineral density (BMD) of the total hip region was measured using Dual X-ray Absorptiometry (DXA) at screening and at month 12.

    A DXA scanner is a device that uses x-ray beams to measure the amount of minerals in the bone.



Secondary Outcome Measures:
  • Change in Bone Mineral Density of the Lumbar Spine at 6 Months [ Time Frame: Screening (day -21 to -1) and month 6 ] [ Designated as safety issue: No ]

    Change in bone mineral density (BMD) of the lumbar spine was measured using Dual X-ray Absorptiometry (DXA) at screening and at month 6.

    A DXA scanner is a device that uses x-ray beams to measure the amount of minerals in the bone.


  • Change in Bone Mineral Density of the Femoral Neck at 6 Months [ Time Frame: Screening (day -21 to -1) and month 6 ] [ Designated as safety issue: No ]

    Change in bone mineral density (BMD) of the femoral neck was measured using Dual X-ray Absorptiometry (DXA) at screening and at month 6.

    A DXA scanner is a device that uses x-ray beams to measure the amount of minerals in the bone.


  • Change in Bone Mineral Density of the Total Hip at 6 Months [ Time Frame: Screening (day -21 to -1) and month 6 ] [ Designated as safety issue: No ]
    Change in bone mineral density (BMD) of the total hip was measured using Dual X-ray Absorptiometry (DXA) at screening and at month 6. A DXA scanner is a device that uses x-ray beams to measure the amount of minerals in the bone.

  • Change in Bone Mineral Density of the Femoral Neck at 12 Months [ Time Frame: Screening (day -21 to -1) and month 12 ] [ Designated as safety issue: No ]

    Change in bone mineral density (BMD) of the femoral neck was measured using Dual X-ray Absorptiometry (DXA) at screening and at month 12.

    A DXA scanner is a device that uses x-ray beams to measure the amount of minerals in the bone.


  • Change in Bone Mineral Density of the Lumbar Spine at 24 Months [ Time Frame: Screening (day -21 to -1) and month 24 ] [ Designated as safety issue: No ]

    Change in bone mineral density (BMD) of the lumbar spine was measured using Dual X-ray Absorptiometry (DXA) at screening and at month 24.

    A DXA scanner is a device that uses x-ray beams to measure the amount of minerals in the bone.


  • Change in Bone Mineral Density of the Total Hip Region at 24 Months [ Time Frame: Screening (day -21 to -1) and month 24 ] [ Designated as safety issue: No ]

    Change in bone mineral density (BMD) of the total hip region was measured using Dual X-ray Absorptiometry (DXA) at screening and at month 24.

    A DXA scanner is a device that uses x-ray beams to measure the amount of minerals in the bone.


  • Change in Bone Mineral Density of the Femoral Neck at 24 Months [ Time Frame: Screening (day -21 to -1) and month 24 ] [ Designated as safety issue: No ]

    Change in bone mineral density (BMD) of the femoral neck was measured using Dual X-ray Absorptiometry (DXA) at screening and at month 24.

    A DXA scanner is a device that uses x-ray beams to measure the amount of minerals in the bone.


  • Course of Disease in Multiple Sclerosis Patients [ Time Frame: Screening (day -21 to -1) and month 12 ] [ Designated as safety issue: No ]
    The course of disease in Multiple Sclerosis (MS) patients was measured comparing results from the Expanded Disability Status Scale (EDSS) from screening and month 12. EDSS is a scale, ranging from 0 (normal) to 10 (death due to MS) for assessing neurologic impairment in MS. It is based on a weighting scheme of eight functional systems. The functional systems are Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel&Bladder, Cerebral and Other functions. EDSS was assessed by the treating neurologist.

  • Adverse Events and Serious Adverse Events Comparison of Treatment Groups [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
    Adverse Events and Serious Adverse events are reported in the safety section.


Enrollment: 29
Study Start Date: October 2010
Study Completion Date: June 2012
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Zoledronic Acid
Participants received zoledronic acid infusion in addition to calcium and vitamin D
Drug: Zoledronic Acid
Zoledronic acid 5 mg once a year via intravenous infusion
Dietary Supplement: Calcium and Vitamin D combination
Calcium 500 mg and Vitamin D 400 IU combined tablet, taken orally twice a day
Placebo Comparator: Placebo
Participants received placebo to zoledronic acid infusion in addition to calcium and vitamin D
Drug: Placebo
Placebo to zoledronic acid once a year via intravenous infusion
Dietary Supplement: Calcium and Vitamin D combination
Calcium 500 mg and Vitamin D 400 IU combined tablet, taken orally twice a day

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01166178

Locations
Germany
Novartis Investigative Site
Bamberg, Germany
Novartis Investigative Site
Berlin, Germany
Novartis Investigative Site
Bochum, Germany
Novartis Investigative Site
Hamburg, Germany
Novartis Investigative Site
Heidelberg, Germany
Novartis Investigative Site
Kassel, Germany
Novartis investigative site
Leipzig, Germany
Novartis Investigative Site
Leverkusen, Germany
Novartis investigative site
Ludwigshafen, Germany
Novartis investigative site
Magdeburg, Germany
Novartis investigative site
Muenchen, Germany
Novartis investigative site
Numbrecht, Germany
Novartis investigative site
Oldenburg, Germany
Novartis Investigative Site
Siegen, Germany
Novartis investigative site
Stade, Germany
Sponsors and Collaborators
Novartis
Investigators
Study Director: Novartis Pharmceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis
ClinicalTrials.gov Identifier: NCT01166178     History of Changes
Other Study ID Numbers: CZOL446HDE40, 2009-011888-37
Study First Received: July 19, 2010
Results First Received: June 3, 2013
Last Updated: October 24, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Novartis:
Multiple Sclerosis
Osteoporosis
Zoledronic Acid

Additional relevant MeSH terms:
Multiple Sclerosis
Osteoporosis
Sclerosis
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Pathologic Processes
Zoledronic acid
Calcium, Dietary
Vitamin D
Ergocalciferols
Diphosphonates
Vitamins
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on July 31, 2014