Zoledronic Acid in MS-patients With Osteoporosis - Full Text View

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: Quadruple (Participant, Care Provider, 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:

Genetics Home Reference related topics: multiple sclerosis

MedlinePlus related topics: Bone Density Minerals Multiple Sclerosis Osteoporosis

Drug Information available for: Zoledronic acid

U.S. FDA Resources

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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years to 75 Years (Adult, Senior)
Sexes Eligible for Study:	All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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


Responsible Party:	Novartis
ClinicalTrials.gov Identifier:	NCT01166178 History of Changes
Other Study ID Numbers:	CZOL446HDE40 2009-011888-37 ( EudraCT Number )
First Submitted:	July 19, 2010
First Posted:	July 20, 2010
Results First Submitted:	June 3, 2013
Results First Posted:	November 26, 2013
Last Update Posted:	November 26, 2013
Last Verified:	October 2013

Keywords provided by Novartis:


Multiple Sclerosis Osteoporosis Zoledronic Acid

Additional relevant MeSH terms:


Sclerosis Multiple Sclerosis Osteoporosis Pathologic Processes 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 Vitamins Vitamin D Ergocalciferols Zoledronic acid Calcium, Dietary Diphosphonates Micronutrients Growth Substances Physiological Effects of Drugs Bone Density Conservation Agents

Zoledronic Acid in MS-patients With Osteoporosis (EXALT)