Multiple Sclerosis
Conditions
Keywords
Multiple Sclerosis, MS, Mitoxantrone, Dexrazoxane, Cardioxane, cardiotoxicity, cardiac toxicity, cardiotoxic side effects, cardiac MRI, cranial MRI, LVEF, neurological outcome
Brief summary
This study will primarily address the question whether the combination of Mitoxantrone therapy with dexrazoxane can reduce cardiotoxic side effects in the treatment of Multiple Sclerosis patients in comparison to Mitoxantrone monotherapy.
Detailed description
It is designed to provide clinical and paraclinical efficacy and safety data for dexrazoxane in Mitoxantrone treatment of Multiple Sclerosis in order to investigate the possible positive influence of dexrazoxane on cardiac function of Mitoxantrone-affected myocardial tissue and on the possible augmented clinical efficacy of Mitoxantrone in combination with dexrazoxane on neurological outcome parameters. The incidence of cardiotoxicity during combined Mitoxantrone/dexrazoxane treatment will be investigated and compared to the standard Mitoxantrone-treatment without dexrazoxane.
Interventions
DRUGDexrazoxane (DRZ) plus Mitoxantrone (MX)
Dosage: DRZ (600 mg/m2) : MX (12 mg/m2) ratio 50:1 DRZ infusion / MX infusion once every three months over a period of 12 months, i.e. 5 infusions
DRUGPlacebo plus Mitoxantrone (MX)
MX Dosage: 12mg/m2 Placebo infusion / MX infusion once every three months over a period of 12 months, i.e. 5 infusions
Sponsors
PD Dr. Andrew Chan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Written informed consent to participate in the study * Male or female subject is 18 years of age to 55 years of age * Subject must have one of the below mentioned confirmed diagnoses of Multiple Sclerosis: RRMS or CPMS according to rev. McDonald Criteria (2005) * If female of childbearing potential: Will to practice reliable birth control measures during study treatment and for at least 6 months after completion of study medication; not lactating or pregnant; and has a documented negative pregnancy test result within 72 hours prior to study medication administration. Male study participants: Will to practice reliable birth control measures during study treatment and for at least 6 months after completion of study medication * Subject is willing to participate in the study, follow protocol study treatment regimen, and comply with all planned assessments * Mitoxantrone treatment indication is given according to current guidelines: * Relapsing progressive or secondary progressive MS with/without superimposed relapses * EDSS 3-6; EDSS deterioration ≥1 point over last 18 months or 2 relapses * non-response or non-tolerability of pre-treatment * ≥ 48 mg/m² BSA MX dose received up to baseline visit as lifetime dosage before study entry. If the patient is under regular ongoing MX treatment, the infusion interval of 3 months must be obtained (see
Exclusion criteria
)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in LVEF in the different treatment arms by cardiac MRI | Baseline to month 12 | Assessment of cardiac function by measurement of LVEF in mitoxantrone plus dexrazoxane treatment arm versus mitoxantrone plus placebo treatment arm by cardiac MRI |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in magnetic evoked potentials: prolongation of TMCT+CMCT, potential configuration | Baseline and month 3,6,9 and month 12 | — |
| Annual brain atrophy rates in cMRI | Day 1 and month 12 | — |
| Changes in transcranial sonography (abnormal iron deposition AID). AID in cMRI. Comparison of both methods | Baseline and month 12 | — |
| Analysis of ABD transporter gene polymorphisms as predictor of therapy response and side effect profile via TaqMan PCR | Baseline and month 12 | — |
| Quality of Life by SF-36 questionnaire | Baseline and month 3,6,9 and month 12 | — |
| Determination of EDSS and relapse rate in mitoxantrone plus dexrazoxane treatment arm versus mitoxantrone plus placebo treatment arm | Baseline and month 3,6,9,12 and 24 | Comparison of clinical efficacy of mitoxantrone plus dexrazoxane treatment versus mitoxantrone plus placebo treatment on neurological outcome parameters by means of EDSS and relapse rate |
| Cumulative number of active lesions by cMRI | Day1 and month 12 | — |
| LVEF in 3D-echocardiography vs. LVEF in cardiac MRI | Baseline and month 12 | — |
| Clinical efficacy of DRZ+MX vs. MX monotherapy by MSFC | Baseline and month 3,6,9,12 and 24 | — |
| Changes in LVEF by transthoracic echocardiography and determination of cardiac side effects by ECG and by measurement of CK-MB, Troponin and BNP in mitoxantrone plus dexrazoxane versus mitoxantrone plus placebo treatment arms | Baseline and month 3,6,9,12, 24 | Assessment of cardiac function by measurement of LVEF by transthoracic echocardiography, by determination of cardiac side effects by ECG and by measurement of CK-MB, Troponin and BNP in mitoxantrone plus dexrazoxane treatment arm versus mitoxantrone plus placebo treatment arm |
Countries
Germany
Outcome results
None listed