Study of Mesenchymal Autologous Stem Cells as Regenerative Treatment for Multiple Sclerosis
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 18
- 试验地点
- 4
- 主要终点
- Neurophysiological parameters - Combined evoked potentials
研究概览
简要总结
The primary objective of the study is to investigate neuroregenerative efficacy (proof of concept) of intrathecal treatment with autologous MSCs as measured by neurophysiological parameters in patients with progressive MS.
Secondary objectives are to assess neuroregenerative efficacy as measured by other neurophysiological parameters as well as clinical, opthalmological and MRI modalities, and to assess safety of the treatment procedure.
详细描述
Prospective, interventional, randomized, placebo-controlled, cross-over study. Patients are randomized to either treatment arm A or B.
Patients in both treatment arms receive intrathecal autologous MSCs, arm A at baseline and arm B at six months.
All patients undergo bone marrow (BM) aspiration prior to baseline. Patients in treatment arm A receive intrathecal autologous MSCs whereas patients in treatment arm B receive placebo. The treatment is blinded for the patients. The BM aspirate from patients in treatment arm B is processed, cryopreserved and stored in a biobank.
At six months, all patients undergo a second BM aspiration. Patients in treatment arm A now receive placebo. The BM aspirate from patients in treatment arm A is processed, cryopreserved and stored in a biobank. Patients in treatment arm B receive intrathecal autologous MSCs. The treatment is blinded for the patients.
Primary outcome is assessed at six months and secondary outcomes are assessed at six, twelve and eighteen months post baseline. Investigator assessing outcomes are blinded to patient treatment allocation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 to ≤55, both genders
- •Diagnosis of secondary progressive or primary progressive MS using revised McDonald criteria of clinically definite MS
- •An EDSS score of 4 to 7
- •Disease duration 2 - 15 years
- •Signed, written informed consent
排除标准
- •Any illness or prior/ongoing treatment that in the opinion of the investigators would jeopardize the ability of the patient to tolerate autologous stem cell treatment
- •Any ongoing infection, including Tbc, CMV, EBV, HSV, VZV, hepatitis virus, toxoplasmosis, HIV or syphilis infections, as well as heaptitis B surface antigen positivity and/or hepatitis C PCR positivity
- •Current immunomodulatory/immunosuppressive treatment
- •Immunomodulatory/immunosuppressive treatment within 6 months prior to inclusion. This includes, but is not restricted to treatment with natalizumab, fingolimod, dimetylfumurat, glatiramer acetate, interferon beta medications, teriflunomide, and siponimod.
- •Treatment with kladribin, ocrelizumab, rituximab, and alemtuzumab within 12 months prior to inclusion
- •Treatment with hematopoietic stem cell therapy within 12 months prior to inclusion
- •Treatment with glucocorticoids or ACTH within three months prior to start of inclusion
- •Having experienced an MS relapse within 2 years prior to study inclusion
- •Current treatment with fampridin
- •History of malignancy other than basal cell carcinoma of the skin or carcinoma in situ that has been in remission for more than one year
- •Severely limited life expectancy by another co-morbid illness
- •History of previous diagnosis of myelodysplasia or previous hematologic disease (including lymphoproliferative disease, bone marrow insufficiency or previous lymphoid irradiation) or current clinically relevant abnormalities of white blood cell counts
- •Immunocompromised patients
- •Estimated glomerular filtration rate <60 ml/min/1.73 m2 or known renal failure
- •Bleeding or clotting diathesis or the use of antithrombotic or anticoagulative treatment
- •Platelet (thrombocyte) count <100 x 10*9/L
- •Participation in another experimental clinical study within the preceding 12 months
- •Contraindications to MRI
- •Prior or current major depression
- •Prior or current psychiatric illness, mental deficiency or cognitive dysfunction influencing the patient ability to make an informed consent or comply with the treatment and follow-up phases of this protocol.
- •Pregnancy or risk of pregnancy (this includes patients that are unwilling to practice active contraception during the duration of the study), breastfeeding or lactation
- •History of autologous/allogenic bone marrow transplantation or peripheral blood cell transplant
- •Known hypersensitivity against paracetamol, codein or xylocain
- •Diagnosis or strong suspicion of polyneuropathy
- •Prior or current alcohol or drug dependencies
- •Inability to give informed consent
研究组 & 干预措施
Arm A - Crossover with MSCs at baseline and placebo at 6 months
Receives mesenchymal stem cells at baseline and placebo at 6 months
干预措施: MSCs (Other)
Arm A - Crossover with MSCs at baseline and placebo at 6 months
Receives mesenchymal stem cells at baseline and placebo at 6 months
干预措施: Saline (Drug)
Arm B - Crossover with placebo at baseline and MSCs at 6 months
Receives placebo at baseline and mesenchymal stem cells at 6 months
干预措施: MSCs (Other)
Arm B - Crossover with placebo at baseline and MSCs at 6 months
Receives placebo at baseline and mesenchymal stem cells at 6 months
干预措施: Saline (Drug)
结局指标
主要结局
Neurophysiological parameters - Combined evoked potentials
时间窗: 6 months
Somatosensoric evoked potentials (SEP) + visual evoked potentials (VEP) + motor evoked potentials (MEP), latency (ms) and amplitude (mV)
次要结局
- MR- Brain volumes(6 and 12 months)
- Expanded disability status scale(6, 12 and 18 months)
- Neurophysiological parameters - Somatosensoric evoked potantials(6 and 12 months)
- Neurophysiological parameters - Motor evoked potentials(6 and 12 months)
- Visual function(6, 12 and 18 months)
- Rate and nature of adverse- and serious adverse events(6, 12 and 18 months)
- Neurophysiological parameters - Visual evoked potentials(6 and 12 months)
- MRI-Lesion volumes(6 and 12 months)
- Patient reported outcomes (PROs)(6, 12 and 18 months)
- Nine-Hole-Peg Test (9-HPT)(6, 12 and 18 months)
- Timed 25 Foot Walk (T25FW)(6, 12 and 18 months)
- Optical coherence tomography (OCT)(6, 12 and 18 months)