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ACTUALITATI IN TERAPIA SCLEROZEI MULTIPLE Caciulata 2007

Dr. Damian Irene Spitalul Clinic CF Constanta. ACTUALITATI IN TERAPIA SCLEROZEI MULTIPLE Caciulata 2007.

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ACTUALITATI IN TERAPIA SCLEROZEI MULTIPLE Caciulata 2007

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  1. Dr. Damian Irene Spitalul Clinic CF Constanta ACTUALITATI IN TERAPIA SCLEROZEI MULTIPLECaciulata 2007

  2. Tratamentul actual standardizat al SM (prevazut in ghidurile de practica medicala, in urma validarii eficacitatii si al profilului lor de siguranta prin studii clinice, conform principiilor medicinei bazate pe dovezi): 1. Tratamente care modifică evoluţia bolii În prezent, pe plan internaţional sunt acceptate ca fiind medicamente care modifică evoluţia bolii următoarele: 1.1. Imunomodulatoare: A. Interferonii beta: interferonul beta la (REBIF), cu administrare s.c. 3 doze pe săptămână interferonul beta la (AVONEX), cu administrare i.m. 1 doză pe săptămână interferonul beta lb (BETAFERON), cu administrare s.c, 1 doză la 2 zile B. Glatiramerul acetat ( COPAXONE ), cu administrare s.c. câte o doză în fiecare zi 1.2. Imunosupresoare:mitoxantrona (Novantrone) Alte forme de tratament imunosupresor care pot fi folosite în tratamentul sclerozei multiple în situaţii particulare nu sunt încadrate şi înregistrate de către autorităţile naţionale şi internaţionale, în concordanţă cu rezultatele studiilor clinice desfăşurate până în prezent, ca agenţi care modifică evoluţia bolii.

  3. Tratamentul actual standardizat al SM Alte tratamente imunomodulatoare (imunoglobulina G administrate i.v., anticorpii monoclonali-natalizumab) sau imunosupresoare (azatioprina, metotrexatul, ciclofosfamida, cladribina, ciclosporina, etc.) nu au demonstrat cert, până în prezent, prin studii controlate, eficacitatea în sensul modificării favorabile a evoluţiei SM. De aceea, ele pot fi folosite în cazuri individuale în care medicul îşi asumă responsabilitatea indicaţiei, a supravegherii siguranţei şi eficacităţii tratamentului. 2. Tratamentul puseului : corticoizi (scad durata şi severitatea puseului şi numărul de leziuni captante de gadolinium la examenul IRM cerebral; folosirea lor însă nu diminuează invaliditatea acumulată prin pusee repetate.) Metilprednisolon în doze mari: 1 gr i.v. în 1-2 h zilnic, timp de 3-5 zile. Cele mai multe protocoale întrerup apoi, brusc, corticoterapia. Dexametazona: 8-12 mg i.v. la 8-12 ore timp de 3-7 zile, urmată de administrare orală

  4. Tratamentul actual standardizat al SM 3. Tratamentul simptomatic şi recuperator Tratamentul simptomatic şi recuperator are ca scop general ameliorarea calităţii vieţii pacienţilor cu SM, cu menţinerea integrării lor sociale cât mai mult timp posibil. El este adaptat în funcţie de stadiul clinic al bolii şi de gradul de invalidare caracteristic fiecărui pacient şi se adresează diferenţiat fiecărui aspect clinic al bolii: invalidarea motorie, disfuncţia sfincteriană, dificultăţile de comunicare, afectarea cognitivă, disfuncţiile emoţionale etc Obiectivele acestor măsuri sunt: prevenirea complicaţiilor bolii, diminuarea handicapului şi limitarea dependenţei pacientului prin optimizarea utilizării resurselor fizice şi psihologice restante Cele mai frecvente simptome asociate sclerozei multiple sunt: tulburările sfincteriene şi de tranzit intestinal oboseală cronică spasticitatea şi contracţiile spastice durerea disfuncţiile cognitive depresia tremorul şi tulburările de echilibru disfuncţiile sexuale simptomele paroxistice şi tulburările motorii

  5. Studii clinice privind etio-patogenia si terapia SM, aflate in desfasurare la aceasta data: 155 studii Cele mai semnificative studii aflate in curs de desfasurare la nivel mondial, in scopul validarii unor noi posibilitati terapeutice in SM: 1.RecruitingCombination Therapy in Patients With Relapsing-Remitting Multiple Sclerosis (MS)CombiRxCondition: Relapsing Remitting Multiple Sclerosis 2.RecruitingSafety Study of RTL1000 (Recombinant T Cell Receptor Ligand) in Subjects With Multiple SclerosisConditions: Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis, Relapsing-Remitting 3.RecruitingEfficacy and Safety of MBP8298 in Subjects With Secondary Progressive Multiple SclerosisCondition: Multiple Sclerosis, Secondary Progressive 4.RecruitingSafety/Effectiveness of Adding Monthly Dexamethasone to Weekly Avonex for MSConditions: Relapsing-Remitting Multiple Sclerosis,; Mono-Symptomatic Multiple Sclerosis 8.RecruitingA Randomised Controlled Trial of Neuroprotection With Lamotrigine in Secondary Progressive Multiple SclerosisCondition: Secondary Progressive Multiple Sclerosis 9.RecruitingEvaluation of Efficiency of Ritalin in Multiple Sclerosis (MS) PatientsConditions: Relapsing Remitting Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive

  6. Studii clinice privind etio-patogenia si terapia SM, aflate in desfasurare la aceasta data 10.RecruitingA Safety Study of Combination Treatment With Avonex and Placebo-Controlled Dosing of Topamax in Relapsing-Remitting Multiple SclerosisCondition: Multiple Sclerosis 11.Not yet recruitingMesenchymal Stem Cells in Multiple Sclerosis (MSCIMS)Condition: Multiple Sclerosis 12.RecruitingEfficacy and Safety of Fingolimod (FTY720) in Patients With Relapsing-Remitting Multiple SclerosisCondition: Multiple Sclerosis 13.RecruitingTrial of Memantine for Cognitive Impairment in Multiple SclerosisConditions: Multiple Sclerosis; Cognition Disorders 18.RecruitingTCV -01-002: T-Cell Vaccination in the Treatment of Probable Multiple SclerosisCondition: Multiple Sclerosis 19.RecruitingAtorvastatin (Lipitor) Therapy in Patients With Clinically Isolated Syndrome (CIS) at Risk for Multiple SclerosisCondition: Multiple Sclerosis 21.RecruitingStudy of SB-683699 Compared to Placebo in Subjects With Relapsing-Remitting Multiple Sclerosis (MS)Condition: Relapsing Remitting Multiple Sclerosis 26.RecruitingBrain Peripheral Benzodiazepine Receptors in Patients With Multiple SclerosisCondition: Multiple Sclerosis

  7. Studii clinice privind etio-patogenia si terapia SM, aflate in desfasurare la aceasta data 27.RecruitingSimvastatin as an Add-on Treatment to Interferon-Beta-1a for the Treatment of Relapsing-Remitting Multiple SclerosisCondition: Multiple Sclerosis 28.RecruitingCranberry for Prevention of Urinary Tract Infections in Multiple Sclerosis PatientsConditions: Multiple Sclerosis; Urinary Tract Infections; Bladder Dysfunction 31.RecruitingUse of Cannabinoids in Patients With Multiple SclerosisCondition: Multiple Sclerosis 32.RecruitingEfficacy of 3,4-DAP in Fatigue Associated With Multiple SclerosisCondition: Multiple Sclerosis 33.RecruitingSafety and Efficacy of Cellcept and Avonex as Combination Treatment in Multiple SclerosisCondition: Multiple Sclerosis 34.RecruitingDonor Stem Cell Transplantation for the Treatment of Multiple SclerosisCondition: Multiple Sclerosis 35.RecruitingVisual Impairment, Oscillopsia and Multiple SclerosisCondition: Multiple Sclerosis 36.Not yet recruitingTrial of Analgesia With Lidocaine or Extended-Release Oxycodone for Neuropathic Pain Treatment in Multiple SclerosisConditions: Neuropathic Pain; Chronic Pain; Multiple Sclerosis

  8. Studii clinice privind etio-patogenia si terapia SM, aflate in desfasurare la aceasta data 41.RecruitingPOPART'MUS: Prevention of Post Partum Relapses With Progestin and Estradiol in Multiple SclerosisCondition: Multiple Sclerosis 42.Not yet recruitingSafety and Efficacy Study of Daclizumab HYP to Treat Relapsing-Remitting Multiple SclerosisCondition: Multiple Sclerosis, Relapsing-Remitting 45.RecruitingStudy of Fampridine-SR Tablets in Multiple Sclerosis PatientsCondition: Multiple Sclerosis 46.RecruitingEfficacy and Safety Evaluation of Nabilone as Adjunctive Therapy to Gabapentin for the Management of Neuropathic Pain in Multiple SclerosisConditions: Neuropathic Pain; Multiple Sclerosis 50.RecruitingAspirin for Treatment of Multiple Sclerosis-Related FatigueCondition: Multiple Sclerosis 53.RecruitingIPX056 in Subjects With Established Spasticity Resulting From Multiple SclerosisCondition: Multiple Sclerosis 54.RecruitingSafety and Tolerability of Interferon-Beta-1a and Estroprogestins Association in MS PatientsCondition: Multiple Sclerosis 56.RecruitingNeuropathic Pain Assessment Comparing Pregabalin and Paroxetine in Management of MS-Induced Neuropathic PainConditions: Neuropathic Pain; Multiple Sclerosis 58.RecruitingNatalizumab Re-Initiation of DosingCondition: Multiple Sclerosis, Relapsing-Remitting

  9. Studii clinice privind etio-patogenia si terapia SM, aflate in desfasurare la aceasta data 60.RecruitingFish Oil for the Treatment of Depression in Patients With Multiple SclerosisConditions: Multiple Sclerosis; Depression 62.RecruitingStudy of Teriflunomide in Reducing the Frequency of Relapses and Accumulation of Disability in Patients With Multiple SclerosisCondition: Multiple Sclerosis 65.RecruitingEARLY IFNb-1a and Atorvastatin Combination Therapy of Isolated Clinical Syndrome Suggestive of Multiple SclerosisCondition: Multiple Sclerosis 66.RecruitingPilot Study of Teriflunomide as Adjunctive Therapy to Interferon-β in Subjects With Multiple SclerosisCondition: Multiple Sclerosis 67.RecruitingPilot Study of Teriflunomide as Adjunctive Therapy to Glatiramer Acetate in Subjects With Multiple SclerosisCondition: Multiple Sclerosis 70.RecruitingStem Cell Therapy for Patients With Multiple Sclerosis Failing Interferon A Randomized StudyCondition: Multiple Sclerosis 71.RecruitingHigh-Dose Immunosuppression and Autologous Transplantation for Multiple Sclerosis (HALT MS) StudyCondition: Multiple Sclerosis 72.RecruitingT-Cell Vaccination in Multiple Sclerosis (MS)Condition: Multiple Sclerosis

  10. Studii clinice privind etio-patogenia si terapia SM, aflate in desfasurare la aceasta data 77.Not yet recruitingA Study in Multiple Sclerosis Patients to Determine the Safety of Different Doses of A4I Compared to Placebo and Their Effects on Multiple Sclerosis LesionsCondition: Multiple Sclerosis 81.RecruitingPlacebo Controlled Study in Subjects With Relapsing Forms of MS to Evaluate the Safety, Tolerability and Effects of CDP323Condition: Multiple Sclerosis 86.RecruitingMinocycline as Add-on to Interferon-Beta-1a (Rebif®) in RRMS (Recycline)Condition: Relapsing-Remitting Multiple Sclerosis94.Not yet recruitingThe Effect of Levetiracetam (Keppra) on the Treatment of Tremor in Multiple SclerosisCondition: Multiple Sclerosis 97.RecruitingA Randomized Placebo-Controlled, Crossover-Design Study of the Effects of Low Dose NaltrexoneCondition: Multiple Sclerosis 98.RecruitingPhase II Cladribine Add-on to Rebif New Formulation in MS Subjects With Active Disease (ONWARD)Condition: Multiple Sclerosis 99.RecruitingFatigue Treatment Using ProvigilCondition: All Multiple SclerosisPatients 100.RecruitingNeuroprotection With Riluzole Patients With Early Multiple SclerosisCondition: Multiple Sclerosis

  11. Studii clinice privind etio-patogenia si terapia SM, aflate in desfasurare la aceasta data 119.RecruitingEffect of Riluzole as a Symptomatic Approach in Patients With Chronic Cerebellar AtaxiaConditions: Hereditary Ataxia; Multiple Sclerosis; Cerebellar Ataxia 120.Not yet recruitingEvaluation of Natalizumab for thE Relief of MS Associated FatiGueCondition: Multiple Sclerosis 127.RecruitingSafety and Tolerability of Rituximab in Neuromyelitis OpticaCondition: Neuromyelitis Optica 133.Not yet recruitingOligodendrocyte Progenitor Cell Culture From Human BrainCondition: Demyelinating Diseases Studii clinice in desfasurare in Romania: 37.RecruitingEfficacy and Safety of BG00012 in Relapsing-Remitting Multiple SclerosisCondition: Relapsing-Remitting Multiple Sclerosis 40.RecruitingEfficacy and Safety Study of BG00012 With Active Reference in Relapsing-Remitting Multiple SclerosisCondition: Relapsing-Remitting Multiple Sclerosis 59.recruitingSafety and Efficacy of Orally Administered Laquinimod for Treatment of Relapsing Remitting Multiple Sclerosis (RRMS)Condition: Multiple Sclerosis

  12. Studii clinice in desfasurare in Romania - detalii Safety and Efficacy of Orally Administered Laquinimod for Treatment of Relapsing Remitting Multiple Sclerosis (RRMS Purpose Determination the efficacy of daily oral treatment with laquinimod 0.6 mg capsules as compared to placebo in subjects with Relapsing Remitting Multiple Sclerosis (RRMS). Condition InterventionPhaseMultiple Sclerosis Drug: Laquinimod Drug: PlaceboPhase IIIPrimary Outcome Measures:  Relapse Rate: Number of confirmed relapses during the double blind study period. [Time Frame: 24 months] Secondary Outcome Measures:  Accumulation of physical disability measured by the time to confirmed progression of EDSS during the study period. [Time Frame: 24 months] MRI Outcomes [Time Frame: 12, 24 months] Total Enrollment:  1000 Study start: September 2007 ArmsAssigned Interventions1: Experimental Drug: Laquinimod Laquinimod 0.6 mg capsule, oral, once daily  2: Placebo Comparator Drug: Placebo  Multinational, multicenter, randomized, double-blind, parallel-group, placebo-controlled study, to evaluate the efficacy, tolerability and safety of daily oral administration of laquinimod 0.6mg in RRMS subjects. Eligible subjects will be equally randomized into one of the following treatment and placebo study groups. Subjects will be regularly evaluated at study sites including physical and neurological medical evaluation, clinical laboratory testing and medical imaging evaluation. Eligibility Ages Eligible for Study:  18 Years   -   55 Years,  Genders Eligible for Study:  Both Criteria Inclusion Criteria: Between 18 and 55 years of age Confirmed MS diagnosis with a relapsing-remitting disease course as defined by the Revised McDonald criteria Ambulatory with converted Kurtzke EDSS score of 0-5.5. Exclusion Criteria: MS diagnosis including progressive forms of MS Women who are pregnant or breastfeeding

  13. Studii clinice in desfasurare in Romania - detalii Efficacy and Safety of BG00012 in Relapsing-Remitting Multiple Sclerosis Purpose : To determine if treatment with BG00012 can decrease the number of MS relapses during a certain time period. To determine if, over time, BG00012 treatment can decrease the number of certain types of brain lesions commonly seen in MS patients and slow down the time it takes for the disease to get worse. The purpose of this study is also to determine the safety of BG00012 and how well it is tolerated. Another goal is to see what effect BG00012 may have on tests and evaluations used to assess MS. Primary Outcome Measures:  To determine if BG00012 is effective in reducing the proportion of relapsing subjects at 2 years. Secondary Outcome Measures:  There are multiple secondary outcomes. Total Enrollment:  1011 Study start: January 2007 Eligibility Ages Eligible for Study:  18 Years   -   55 Years,  Genders Eligible for Study:  Both Inclusion Criteria: Unless otherwise specified, to be eligible to participate in this study, candidates must meet the following eligibility criteria at the time of the randomization: Aged 18 to 55 years old, inclusive, at the time of informed consent. Must have a confirmed diagnosis of RRMS according to McDonald criteria #1-4. Must have a baseline EDSS between 0.0 and 5.0, inclusive. Must have relapsing-remitting disease course. Exclusion Criteria: Unless otherwise specified, candidates will be excluded from study entry if any of the following exclusion criteria exist at randomization: Other chronic disease of the immune system, malignancies, acute urologic, pulmonary, gastrointestinal disease. Pregnant or nursing women.

  14. Noi posibilitati terapeutice in SM:- Terapia cu celule stem- Vaccinuri premise etio-patogenice principiile metodelor stadiul rezultatelor actuale studii clinice in desfasurare (detalii)

  15. Noi posibilitati terapeutice in SM:Terapia cu celule stemstudii clinice in desfasurare (detalii) Mesenchymal Stem Cells in Multiple Sclerosis (MSCIMS) Sponsors and Collaborators:University of Cambridge Cambridge University Hospitals NHS Foundation Trust.Medical Research Council Purpose Hypothesis: Intravenous administration of bone marrow-derived autologous adult human mesenchymal stem cells is a safe novel therapeutic approach for patients with multiple sclerosis Mesenchymal Stem Cells in Multiple Sclerosis (MSCIMS) is a phase I/IIA trial designed to establish the safety of intravenous administration of bone marrow-derived autologous adult human mesenchymal stem cells to patients with multiple sclerosis. Study Type: InterventionalStudy Design: Treatment, Non-Randomized, Open Label, Historical Control, Crossover Assignment, Safety/Efficacy Study Official Title: Autologous Adult Human Mesenchymal Stem Cells: a Neuroprotective Therapy for Multiple Sclerosis Further study details as provided by University of Cambridge: Primary Outcome Measures:  Adverse events Secondary Outcome Measures:  Visual function (acuity and colour) Visual evoked potential latency Optic nerve Magnetisation Transfer Ratio Retinal nerve fibre layer thickness (by optical coherence tomography) Brain lesion Magnetisation Transfer Ratio MRI brain T1 hypointensity load T cell response suppression Multiple Sclerosis Functional Composite Score Expanded Kurtzke Disability Status Score

  16. Noi posibilitati terapeutice in SM:Terapia cu celule stemstudii clinice in desfasurare (detalii) Total Enrollment:  20 Disease under investigation: Multiple Sclerosis Phase: I/IIA Number of patients: 20 Design: 1 year cross over, single treatment at 6 months Intervention: Administration of bone marrow-derived autologous mesenchymal stem cells Route of administration: Intravenous Dose: 2,000,000 Mesenchymal Stem Cells per kilogram Source of patients: Referrals accepted from Neurologists in East Anglia and North London, UK Referral Criteria: (all 4 required) Clinically definite multiple sclerosis Disease duration 2 - 15 years Expanded Kurtzke Disability Status Score 2.0 - 5.5 (inclusive) Evidence of optic nerve damage by history of optic neuritis, or relative afferent pupillary defect, or optic atrophy on fundoscopy, or abnormal visual evoked potential from either or both eyes suggestive of demyelination Eligibility Ages Eligible for Study:  18 Years   -   50 Years,  Genders Eligible for Study:  Both Inclusion Criteria: Clinically definite multiple sclerosis Disease duration 2 - 15 years Expanded Kurtzke Disability Status Score 2.0 - 5.5 Evidence of optic nerve damage by: history of optic neuritis, or relative afferent pupillary defect, or optic atrophy on fundoscopy, or abnormal visual evoked potential from either or both eyes suggestive of demyelination Prolonged visual evoked potential P100 latency with preserved waveform T2 lesion on MRI optic nerve <40% loss of retinal nerve fibre layer thickness on optical coherence tomography Exclusion Criteria: Age < 18 years Age > 50 years Patient lacks capacity to give informed consent Presence of a severe bleeding disorder Planning a pregnancy during the trial period Current MS disease modifying therapy Location and Contact Information Please refer to this study by ClinicalTrials.gov identifier  NCT00395200 Siddharthan Chandran, MBChB, PhD      +44 (0) 1223 331160    sc222@cam.ac.uk

  17. Noi posibilitati terapeutice in SM:Terapia cu celule stemstudii clinice in desfasurare (detalii) Donor Stem Cell Transplantation for the Treatment of Multiple Sclerosis Purpose While the cause of MS in not known, there is an autoimmune component that destroys nerve cells. Autoimmunity is a condition where an individual's immune system attacks his/her own cells. Bone marrow stem cell transplantation has been shown to halt autoimmunity. Stem cell transplant can be performed using the patient’s own cells, or donor cells. The general consensus in the field is that donor transplant is most likely to halt disease progression. This study is designed to evaluate the safety of a donor transplant procedure as a therapy for relapsing remitting multiple sclerosis (RRMS). Two factors limit the widespread application of traditional donor stem cell transplant: 1) preparing the patient for transplant (conditioning); and 2) graft-versus-host disease (GVHD). Traditional conditioning destroys the recipient's immune system and requires that the marrow transplant be successful because the patient is unable to fight off infection if the donor cells do not survive. GVHD occurs when donor immune cells recognize the recipient’s cells as foreign tissue and attack them. Severe GVHD can result in death. This study utilizes a new approach to conditioning which leaves the patient's immune system intact. The transplant product is depleted of GVHD-producing cells but retains tolerance-promoting cells, called facilitating cells, which are intended to ensure the donor and recipient cells coexists peacefully. The toxicity of conditioning and transplantation is significantly reduced. The end result is a marrow system that contains recipient and donor cells, a state called mixed chimerism. In this study, we will determine the appropriate cell dose to safely establish mixed chimerism following partial conditioning in patients with RRMS. The study takes a gradual approach to increasing the cell dose to achieve mixed chimerism. Each patient will receive a cell dose one unit above the dose received by the most recent safely transplanted patient. We believe this study will provide a breakthrough in the treatment of MS. The goal of this proposal is to evaluate the potential of safely establishing mixed chimerism to interrupt the autoimmune process and end the devastating effects of MS. Primary Outcome Measures:  Stem cell engraftment/chimerism Secondary Outcome Measures:  Disease remission Total Enrollment:  15

  18. Noi posibilitati terapeutice in SM:Terapia cu celule stemstudii clinice in desfasurare (detalii) Eligibility Ages Eligible for Study:  18 Years   -   55 Years,  Genders Eligible for Study:  Both Inclusion Criteria: Clinically definite MS according to the McDonald criteria Confirmed diagnosis of relapsing-remitting MS. Age between 18 and 55 years Extended Disability Status Score (EDSS) between 0 and 5.0 Relapse within the last year or sustained disability progression of 1.0 for six months Treatment with high dose, high frequency Interferon-β therapy, or failure to tolerate Interferon-β therapy DLCO> 50% (unless cleared by physician) EF > 40% (unless cleared by cardiologist) Required initial laboratory data (obtained within 30 days prior to transplant, unless otherwise specified) HIV-1,2 antigen and antibody negative HBsAg negative (chronic hepatitis B carriers without clinical evidence of liver disease can be considered on an individual basis if it is determined that the added risk is justified by the prognosis and lack of treatment alternatives) Hepatitis C antibody negative (positive antibody allowed if antigen (RNA)-negative and no clinical evidence of cirrhosis) CMV, hepatitis B, HTLV-1,2, EBV, and Herpes antibody status known Pregnancy test negative No life-threatening organ dysfunction. Uncontrolled or severe cardiovascular disease, including recent (<6 months) myocardial infarction, angina (symptomatic despite optimal medical management), life-threatening arrhythmia or hypertension Able to give informed consent Exclusion Criteria: Women who are of child bearing potential must have a negative pregnancy test (serum pregnancy test [HCG]) within 48 hours of initiating total body irradiation and agree to use reliable contraception for 1 year following transplant. Concomitant severe diseases (respiratory, renal, liver, cardiac failures, psychiatric disorders, neoplasms) Recurrent urinary, pulmonary infections. Active bacterial, viral, or fungal infection Active peptic ulcer disease Previous treatments with total lymphoid irradiation or total body irradiation Interferon-neutralizing antibody positive with a titer greater than 20 Relapse in the month preceding enrollment Poor compliance Location and Contact Information United States, Kentucky      Institute for Cellular Therapeutics, University of Louisville, Louisville,  Kentucky,  40202,  United States; 

  19. Noi posibilitati terapeutice in SM:Terapia cu celule stemstudii clinice in desfasurare (detalii) Stem Cell Therapy for Patients With Multiple Sclerosis Failing Interferon A Randomized Study Total Enrollment:  110 Study start: January 2006 To assess the efficacy of autologous PBSCT versus FDA approved standard of care ( i.e. interferon, copaxone, or mitoxantrone) for inflammatory multiple sclerosis failing interferon therapy. The endpoints to be considered in this study are: Eligibility Ages Eligible for Study:  18 Years   -   55 Years,  Genders Eligible for Study:  Both Criteria Inclusion Criteria: Age between 18-55, inclusive. Diagnosis of MS using Poser criteria of “clinically definite” MS (Appendix A). An EDSS of 2.0 to 6.0 (Appendix B). Inflammatory disease despite primary disease modifying therapy with at least 4 months of interferon. Inflammatory disease is defined by either MRI showing gadolinium enhancing lesions or clinically as acute relapses treated with IV solumedrol. Failure is defined as two or more clinical relapses with documented neurologic changes within the year prior to the study. (NOTE: Relapses must have required treatment with corticosteroids). Failure may also be defined as one relapse within the year prior to study if there is evidence on MRI of active inflammation (i.e., gadolinium enhancement). Exclusion criteria Inability or unwillingness to pursue effective means of birth control. Effective birth control is defined as 1) refraining from all acts of vaginal intercourse (ABSTINENCE); 2) consistent use of birth control pills; 3) injectable birth control methods (Depo-provera, Norplant); 4) tubal sterilization or male partner who has undergone vasectomy; 5) placement of an IUD (intrauterine device); or 6) use, with every act of intercourse, of diaphragm with contraceptive jelly and/or condoms with contraceptive foam. Failure to willingly accept or comprehend irreversible sterility as a side effect of therapy. FEV1/FVC < 60% of predicted after bronchodilator therapy (if necessary). DLCO < 50% of predicted. Resting LVEF < 50 %. Bilirubin > 2.0 mg/dl. Serum creatinine > 2.0 mg/dl. Known hypersensitivity to mouse, rabbit, or E. Coli derived proteins, or to iron compounds/medications. Presence of metallic objects implanted in the body that would preclude the ability of the patient to safely have MRI exams. Diagnosis of primary progressive MS. Platelet count < 100,000/ul, WBC < 1,500 cells/mm3. Psychiatric illness, mental deficiency or cognitive dysfunction making compliance with treatment or informed consent impossible. Active infection except asymptomatic bacteruria. Location and Contact Information Please refer to this study by ClinicalTrials.gov identifier  NCT00273364 United States, Illinois      Northwestern University, Feinberg School of Medicine, Chicago,  Illinois,  60611,  United States; Recruiting Dzemila Spahovic, MD  312-908-0059    d-spahovic@northwestern.eduRichard Burt, MD,  Principal Investigator

  20. Noi posibilitati terapeutice in SM:Terapia cu celule stemstudii clinice in desfasurare (detalii)High-Dose Immunosuppression and Autologous Transplantation for Multiple Sclerosis (HALT MS) Study Purpose The purpose of this study is to determine the effectiveness of a new treatment for multiple sclerosis (MS), a serious disease in which the immune system attacks the brain and spinal cord. MS can be progressive and severe and lead to significant disability. The study treatment involves the use of high-dose chemotherapeutic drugs to suppress the immune system. The participant’s own (autologous) blood-forming (hematopoietic, CD34+) stem cells are collected before the chemotherapy is given, and then transplanted back into the body following treatment. Transplantation of autologous hematopoietic stem cells is required to prevent very prolonged periods of low blood cell counts after the high-dose chemotherapy. Phase IITotal Enrollment:  30 Eligibility Ages Eligible for Study:  18 Years   -   60 Years,  Genders Eligible for Study:  Both Inclusion Criteria: Diagnosis of relapsing-remitting or progressive-relapsing multiple sclerosis for less than 10 years using McDonald Criteria. More information on this criterion can be found in the protocol. Score between 3.0 and 5.5 on the Expanded Disability Status Scale (EDSS) T2 abnormalities on brain MRI consistent with MS Two or more relapses in 12 months time on interferon (IFN), glatiramer acetate (GA), or mitoxantrone with EDSS increase greater than 0.5, maintained for greater than 3 months OR one relapse on IFN, GA, or mitoxantrone, together with MRI changes consistent with poor prognosis. On IFN or GA for at least 6 months before the relapses occur that are counted to satisfy previous inclusion criterion OR have received at least 3 doses of mitoxantrone on a treatment schedule before the relapses occur that are counted to satisfy previous inclusion criterion Approval by an MS Review Panel to participate in the study. More information on this criterion can be found in the protocol. In good clinical condition with adequate organ function and without coexisting medical problems that would increase the risk to the participant Willing to use acceptable methods of contraception Willing and able to comply with all study requirements Willing to accept and comprehend irreversible sterility as side effect of therapy Exclusion Criteria: Primary progressive MS Secondary progressive MS without relapses (i.e., progression without exacerbations or relapses) for 12 or more months Neuromyelitis optica, a disease similar to MS Initiation of new immunosuppressant treatment after the participant becomes eligible for the protocol or continuance of immunosuppressant drugs after the participant is screened for the protocol. Treatment with IFN, GA, or corticosteroids is permitted after the participant becomes eligible for the protocol. Lapse of greater than 4 months between the time a participant is eligible for the protocol and initiation of protocol treatment except when judged acceptable by the MS Review Panel Prior treatment with investigational immunosuppressive agents within 3 months of study eligibility Prior treatment with natalizumab History of cytopenia consistent with the diagnosis of myelodysplastic syndrome (MDS) Active hepatitis B or C infection, cirrhosis, or HIV infection Uncontrolled diabetes mellitus Uncontrolled viral, fungal, or bacterial infection. Patients with asymptomatic bacteriuria are not excluded. Any illness that would jeopardize the ability to tolerate aggressive chemotherapy Prior history of malignancy, except localized basal cell or squamous skin cancer. Other malignancies for which the subject is judged cured by the administered therapy will be considered on an individual basis. Hypersensitivity to mouse, rabbit, or Escherichia coli-derived proteins or to iron compounds/medications Metallic objects implanted in the body that would affect MRI exams Psychiatric illness, mental deficiency, or cognitive dysfunction Pregnancy

  21. Noi posibilitati terapeutice in SM:Terapia cu celule stemstudii clinice in desfasurare (detalii) Oligodendrocyte Progenitor Cell Culture From Human Brain Purpose Recent developments in the understanding of stem- and progenitor cell differentiation raises hopes that brain damage in chronic neurological diseases may become repaired by systemic or focal transplantation of such cells. Clinical trials of stem- or progenitor cell transplantation in multiple sclerosis are currently premature. The researchers developed a protocol for human oligodendrocyte progenitor cell culture from human brain for the treatment of demyelinating disease. Phase I Primary Outcome Measures:  Number of oligodendrocyte progenitor cell differentiation Total Enrollment:  100 Expected completion: March 2008 Eligibility Ages Eligible for Study:  20 Years   -   65 Years,  Genders Eligible for Study:  Both Criteria Inclusion Criteria: Male or female 20-65 years of age Informed consent Has elective craniotomy surgery Exclusion Criteria: HIV, hepatitis, and other central nervous system (CNS) infections Dementia, Alzheimer disease, and neurodegenerative disease

  22. Noi posibilitati terapeutice in SM:Vaccinuristudii clinice in desfasurare (detalii) TCV -01-002: T-Cell Vaccination in the Treatment of Probable Multiple Sclerosis Purpose In the present study, we, the investigators at Sheba Medical Center, intend to evaluate T cell vaccination (TCV) in patients with probable multiple sclerosis (MS) within up to 3 months after the first clinical attack. It is of the utmost importance to evaluate the treatment effects at the onset of disease, i.e. in patients with probable MS, in order to evaluate whether early treatment can prevent the second attack (conversion to definite MS). Moreover, at disease onset, the immunological process of epitope spreading associated with the exposure of the immune system to myelin antigens is still limited. With additional attacks, increased recognition of new self-determinants of encephalitogenic peptides presented to the immune system during the inflammatory process occurs, and enhances further disease activity. The aim of the early TCV treatment approach is to stop this process as early as possible, during the onset of the disease, thus preventing additional attacks and disease progression. We will evaluate the effect of TCV on clinical, immunological and magnetic resonance imaging (MRI) parameters in patients with probable MS. Phase III Study Type: InterventionalStudy Design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Efficacy Study Primary Outcome Measures:  The rate of progression to definite MS (second attack) during the study Time to progression to definite MS (second attack) Secondary Outcome Measures:  Change in the count of new gadolinium (GD) enhancing lesions from two baseline (B) MRIs to the final (F) MRIs Change in total volume of new GD enhancing lesions from two baseline MRIs (B) to the final MRIs (F) The change in neurological disability as measured by the Expanded Disability Status Scale (EDSS)

  23. Noi posibilitati terapeutice in SM:Vaccinuristudii clinice in desfasurare (detalii) Total Enrollment:  80 Inclusion criteria: Age: 15 - 50 years. Three months within the acute onset of neurological symptoms suggestive of the first attack of multiple sclerosis. Diagnosis of CPMS C3 (Poser criteria). Positive brain MRI according to Fazekas criteria. Negative pregnancy test and use of effective contraceptive for female patients who are sexually active. Signed written informed consent. Exclusion criteria: Blood tests suggestive of other autoimmune diseases. Known allergic reactions to MRI contrast media. A clear regression of the neurological symptoms after the first attack that suggests a primary-progressive course. Corticosteroid treatment in the previous 4 weeks (28 days). Previous treatment with immunosuppressive medications such as cyclophosphamide, azathioprine, methotrexate, mitoxantrone or cyclosporine. Previous treatment with interferon beta 1a or 1b, copolymer-1, IVIg, plasmapheresis. Location and Contact Information      Sheba Medical Center, Ramat Gan,  52621,  Israel; 

  24. Noi posibilitati terapeutice in SM:Vaccinuristudii clinice in desfasurare (detalii) T-Cell Vaccination in Multiple Sclerosis (MS) Purpose The purpose of this study is to evaluate the safety of T-cell vaccination in MS patients. Immunization of MS patients with irradiated autologous encephalitogenic myelin peptides (EMP) specific T-cell lines or clones. Clinical immunologic and neuroradiologic evaluation. Primary Outcome Measures:  safety assessment of T-cell vaccination in nonresponding MS patients Phase IPhase IITotal Enrollment:  20 Eligibility Ages Eligible for Study:  16 Years   -   60 Years,  Genders Eligible for Study:  Both Criteria Inclusion Criteria: Definite MS (post criteria) Relapsing remitting or primary progressive clinical course. At least one relapse in the last two years. Disease duration > 1 year Expanded Disability Status Scale (EDSS) between 0-6 Brain magnetic resonance imaging (MRI) compatible with MS Not involved in any other clinical trials No other systemic disease Exclusion Criteria: Does not comply with the above Location and Contact Information       Multiple Sclerosis Center, Ramat Gan,  Israel;

  25. Noi posibilitati terapeutice in SM: Vaccinuri Induction of Antigen-Specific Tolerance in Multiple Sclerosis After Immunization With DNA Encoding Myelin Basic Protein in a Randomized, Placebo-Controlled Phase 1/2 Trial Amit Bar-Or, MD; Timothy Vollmer, MD; Jack Antel, MD; Douglas L. Arnold, MD; Caroline AnitaArch Neurol.2007; Objective  To assess safety and immune modulation by BHT-3009, a tolerizing DNA vaccine encoding full-length human myelin basic protein, in patients with multiple sclerosis (MS). Design  The study was a randomized, double-blind, placebo-controlled trial. Subjects receiving placebo were crossed over into an active arm after treatment unblinding. Setting  The trial was conducted at 4 academic institutions within North America. Patients  Thirty patients with relapsing-remitting or secondary progressive MS who were not taking any other disease-modifying drugs were enrolled in the trial. Further, the patients were required to have either 1 to 5 gadolinium-enhancing lesions on screening brain magnetic resonance imaging (MRI), a relapse in the previous 2 years, or disease worsening in the previous 2 years. Interventions  BHT-3009 was administered as intramuscular injections at weeks 1, 3, 5, and 9 after randomization into the trial, with or without 80 mg of daily oral atorvastatin calcium in combination. Three dose levels of BHT-3009 were tested (0.5 mg, 1.5 mg, and 3 mg). Main Outcome Measures  The primary outcome measures were safety and tolerability of BHT-3009. Secondary outcome measures included the number and volume of gadolinium-enhanced lesions on MRI, relapses, and analysis of antigen-specific immune responses. Results  BHT-3009 was safe and well tolerated, provided favorable trends on brain MRI, and produced beneficial antigen-specific immune changes. These immune changes consisted of a marked decrease in proliferation of interferon-–producing, myelin-reactive CD4+ T cells from peripheral blood and a reduction in titers of myelin-specific autoantibodies from cerebral spinal fluid as assessed by protein microarrays. We did not observe a substantial benefit of the atorvastatin combination compared with BHT-3009 alone. Conclusion  In patients with MS, BHT-3009 is safe and induces antigen-specific immune tolerance with concordant reduction of inflammatory lesions on brain MRI.

  26. Noi posibilitati terapeutice in SM: VaccinuriInduction of Antigen-Specific Tolerance in Multiple Sclerosis After Immunization With DNA Encoding Myelin Basic Protein in a Randomized, Placebo-Controlled Phase 1/2 Trial

  27. CONCLUZII Terapia SM este in continua dezvoltare, paralel cu evolutia intelegerii mecanismelor etio-patogenice ale bolii; O terapie corecta si completa este necesara pentru asigurarea calitatii vietii si a prognosticului vital si dizabilitant

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