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 - EXALT
- Conditions
- osteoporosis in patients with multiple sclerosisMedDRA version: 14.1Level: PTClassification code 10049088Term: OsteopeniaSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disordersMedDRA version: 14.1Level: PTClassification code 10031282Term: OsteoporosisSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
- Registration Number
- EUCTR2009-011888-37-DE
- Lead Sponsor
- ovartis Pharma GmbH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- Not specified
Written informed consent to participate in the trial
2) Males and Females between 18 and 75 years of age
3) Definite diagnosis of multiple sclerosis as defined by 2005 revised McDonald criteria (Appendix 3)
4) MS-subtype: RRMS, SPMS, PPMS
5) EDSS score between 2.5 to 6.5 (including)
6) No immunomodulatory treatment for MS within the last 30 days or stable and well tolerated therapy with any beta-interferon formulation, glatirameracetate or fingolimod for at least 30 days immediately prior to baseline.
7) BMD T-score of less or equal to -2.0 but not less 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 DXA-scan (= 3 months). The DXA-scans for all assessments need to be performed with the same DXA-machine.
8) Previous participation in CZOL446HDE39
9) 25-OH vitamin D level greater or equal to 15 ng/ml
10) Sufficient ability to read, write and communicate comprehensibly and comply to study procedures
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
1) Contraindications against Calcium and Vitamin D according to the summary product characteristics
2) Contraindications against zoledronic acid according to the summary of product characteristics
3) Hypersensitivity to bisphosphonates, Calcium and Vitamin D or to drugs with similar chemical structures
4) More than one osteoporotic fracture
5) Severe disability or any clinical impairment that can prevent the patient to meet all study requirements
6) Concomitant medication with influence on bone mineral density (eg. enzyme-inducing antiepileptics like Carbamazepin, Phenytoin, Phenobarbital, Primidon)
7) Any neurological disorder other than MS which is known to affect bone mineral density (e.g. muscular dystrophy, severe paresis due to other reasons than MS, degenerative nervous disorder, stroke)
8) Any bone disorder other than osteoporosis known to affect bone mineral density (e.g. paget´s disease, osteogenesis imperfecta, multiple myeloma)
9) Study personnel or first degree relatives of investigator(s) must not be included in the study.
10) Women who are
- pregnant or breast feeding (pregnancy defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mlU/ml)).
- menstruating and capable of becoming pregnant* and not practicing two medically approved methods of contraception (Pearl Index < 1**) during and up to at least one year after the end of treatment. A negative pregnancy test (serum) for all women is required with sufficient lead time before inclusion.
*definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH level > 40 mlU/m or 6 weeks post surgical bilateral oophorectomy with or without hysterectomy
**examples of particularly reliable methods with Pearl Index (PI) < 1, according to guidelines of Deutsche Gesellschaft für Gynäkologie und Geburtshilfe:
•Combination pill with estrogen and gestagen (no minipill, PI=0.1-0.9)
•Vaginal ring (NuvaRing®, PI=0.65 uncorr.; 0.4 corr.)
•Contraceptive patch (EVRA®, PI=0.72 uncorr.; 0.9 corr.)
•Estrogen-free ovulation inhibitors (Cerazette®, PI=0.14)
•Progestin-containing contraceptives (Implanon®, PI=0-0.08)
•Injectable 3-month depot progestins (PI=0.3-1.4; 0.88 corr.)
•Intra-uterine progestine device (Mirena®, PI=0.16)
11) Baseline renal insufficiency (calculated creatinine clearance less than 35.0 mL/min); Urine dipstick greater than or equal to 2+ protein at Visit 1 without evidence of contamination or bacteriuria (may be repeated one time at least a week apart if there is suspicion of contamination).
12) Pre-existing hypocalcemia = 2.0 mmol/L (8.0 mg/dL) not adequately treated by intake of calcium and vitamin D before baseline
13) Use of testosterone therapy within one year prior to randomization
14) Use of systemic corticosteroids (oral or i.v.) in the last year with more than 7.5 mg/day prednisolone (or equivalent) continuously for more than four weeks.
NOTE: Use of corticosteroids in forms such as topical creams, nasal or inhaled formulations or those injected locally (eg. intra-articularly, ocular, intrsthecal) or pulsed therapy for MS-relapses are NOT exclusionary.
15) Prior exposure to anabolic steroids or growth hormone within 6 months prior to randomization
16) Treatment with any investigational drug(s) and/or devices within 30 days prior to randomization.
17) Treat
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method