Evaluation of clINical reCovery After a Relapse: a Pilot Study assEssing the Neuronal Effects of D-Aspartate in RR-MS Subjects Treated With IntErferon Beta 1a 44 mcg TIW (INCREASE)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 7
- 试验地点
- 17
- 主要终点
- Number of Participants With Change From Baseline in Multiple Sclerosis Related Disability Measured by Expanded Disability Status Scale (EDSS) at Week 8
研究概览
简要总结
The purpose of this study was to evaluate the improvement in spontaneous recovery from clinical deficits at the time of an acute relapse in RR-MS participants already receiving interferon (IFN) beta 1a with D-aspartate (versus placebo) as add-on therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
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
- •Participants with RR-MS, according to the revised McDonald Criteria (2010)
- •Participants with an expanded disability status scale (EDSS) score between 0 and 3 before screening visit and before relapse
- •Participants receiving treatment with IFN beta 1a 44 mcg three times a week for at least 6 months but for no more than 10 years before the screening visit
- •Female participants must be neither pregnant nor breastfeeding and must lack childbearing potential
- •Participants willing and able to comply with the protocol for the total duration of the study
- •Participants able to understand the purposes and the risks of the study
- •Participants have signed the appropriate written informed consent form, approved by the Independent Ethics Committee (IEC), prior to the performance of any study activities
- •For MS participants with relapse:
- •Deterioration of at least one step in a relevant Functional Systems Scale (FSS) or an increase in EDSS of 1 point or more compatible, according to physician's judgment, with the therapy prosecution
- •Relapse started within maximum 5 days before the inclusion in the study
- •MS participants without relapse with clinically stable RR-MS
排除标准
- •Participants with diagnosis of primary progressive MS (PP-MS)
- •Participants have any disease other than MS that could better explain his/her signs and symptoms
- •Participants with any comorbidity with diseases that might alter synaptic plasticity (example Parkinson Disease, Alzheimer Disease, Stroke)
- •Participants receiving concomitant treatment with drugs that may alter synaptic plasticity (example, cannabinoids)
- •Participants with history or presence of any unstable medical condition (tumor or chronic infection or severe life threatening infection within the last 6 months)
- •Participants who have received any corticosteroids therapy within 3 months prior to the screening
- •Participants with any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressive agents during the course of the study
- •Participants who have received any immunosuppressive agents other to corticosteroids, as monotherapy or combination therapy within 3 months prior to the screening visit
- •Participants with history or currently active primary or secondary immunodeficiency
- •Participants with inadequate liver function, defined by alanine aminotransferase (ALT) > 3 * upper limit of normal (ULN), or alkaline phosphatase (AP) > 2 * ULN, or total bilirubin > 2 * ULN if associated with any elevation of ALT or AP
- •Participants with inadequate bone marrow reserve, defined as a white blood cell count less than 0.5 * lower limit of normal (LLN)
- •Participants with moderate to severe renal impairment
- •Participants unable to complete an magnetic resonance imaging (MRI) (contraindications for MRI include but are not restricted to weight >=140 kilogram (kg), pacemaker, cochlear implants, presence of foreign substances in the eye, intracranial vascular clips, surgery within 6 weeks of entry into the study, coronary stent implanted within 8 weeks prior to the time of the intended MRI, etc)
- •Participants with contraindication to gadolinium (Gd) can be enrolled into the study but cannot receive Gd contrast dyes during their MRI scans
- •Participants receiving supplements that, in the Investigator's opinion, may affect the evaluation of fatigue
- •Participants with any known contraindications or hypersensitivity to D-aspartate or any excipient
- •Participants with any other significant disease that in the Investigator's opinion would impede study assessments or endanger the participant
- •Female participants with positive pregnancy test at baseline or participants with active project of pregnancy during the study
- •Participants with legal incapacity or limited legal capacity
- •Participants have participated in any other investigational study within 8 weeks before the screening visit
研究组 & 干预措施
D-aspartate + IFN beta-1a + Methylprednisolone
Participants received D-aspartate 2660 milligrams (mg) once daily in the form of oral solution for 24 weeks along with IFN beta-1a subcutaneously (sc) at a dose of 44 microgram (mcg) three times a week (TIW) in participants without relapse and IFN beta-1a sc TIW plus Methylprednisolone 1000 mg intravenously once daily for 5 consecutive days in participants with relapse.
干预措施: D-aspartate (Dietary Supplement)
D-aspartate + IFN beta-1a + Methylprednisolone
Participants received D-aspartate 2660 milligrams (mg) once daily in the form of oral solution for 24 weeks along with IFN beta-1a subcutaneously (sc) at a dose of 44 microgram (mcg) three times a week (TIW) in participants without relapse and IFN beta-1a sc TIW plus Methylprednisolone 1000 mg intravenously once daily for 5 consecutive days in participants with relapse.
干预措施: IFN beta-1a (Biological)
D-aspartate + IFN beta-1a + Methylprednisolone
Participants received D-aspartate 2660 milligrams (mg) once daily in the form of oral solution for 24 weeks along with IFN beta-1a subcutaneously (sc) at a dose of 44 microgram (mcg) three times a week (TIW) in participants without relapse and IFN beta-1a sc TIW plus Methylprednisolone 1000 mg intravenously once daily for 5 consecutive days in participants with relapse.
干预措施: Methylprednisolone (Drug)
Placebo + IFN beta-1a + Methylprednisolone
Participants received placebo matched to D-aspartate once daily in the form of oral solution for 24 weeks along with IFN beta-1a subcutaneously (sc) at a dose of 44 microgram (mcg) three times a week (TIW) in participants without relapse and IFN beta-1a sc TIW plus Methylprednisolone 1000 mg intravenously once daily for 5 consecutive days in participants with relapse.
干预措施: Placebo (Drug)
Placebo + IFN beta-1a + Methylprednisolone
Participants received placebo matched to D-aspartate once daily in the form of oral solution for 24 weeks along with IFN beta-1a subcutaneously (sc) at a dose of 44 microgram (mcg) three times a week (TIW) in participants without relapse and IFN beta-1a sc TIW plus Methylprednisolone 1000 mg intravenously once daily for 5 consecutive days in participants with relapse.
干预措施: IFN beta-1a (Biological)
Placebo + IFN beta-1a + Methylprednisolone
Participants received placebo matched to D-aspartate once daily in the form of oral solution for 24 weeks along with IFN beta-1a subcutaneously (sc) at a dose of 44 microgram (mcg) three times a week (TIW) in participants without relapse and IFN beta-1a sc TIW plus Methylprednisolone 1000 mg intravenously once daily for 5 consecutive days in participants with relapse.
干预措施: Methylprednisolone (Drug)
结局指标
主要结局
Number of Participants With Change From Baseline in Multiple Sclerosis Related Disability Measured by Expanded Disability Status Scale (EDSS) at Week 8
时间窗: Baseline, Week 8
EDSS is an ordinal scale in half-point increments that qualifies disability in participants with Multiple Sclerosis (MS). It assesses the 8 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder, cerebral and other) as well as ambulation. EDSS overall score ranging from 0 (normal) to 10 (death due to MS).
次要结局
- Number of Participants With Change From Baseline in Multiple Sclerosis Related Disability Measured by Expanded Disability Status Scale (EDSS) at Week 12 and 24(Baseline, Week 12 and 24)
- 25-foot Timed Walk (25-FWT) to Measure Multiple Sclerosis Related Disability and Cognitive Impairment(At Week 8, 12 and 24)
- 9 Hole Peg Test (9HPT) to Measure Multiple Sclerosis Related Disability and Cognitive Impairment(Week 8, 12 and 24)
- Symbol Digit Modalities Test to Measure Multiple Sclerosis Related Disability and Cognitive Impairment(At Week 8, 12 and 24)
- Low Contrast Letter Visual Acuity Test to Measure Multiple Sclerosis Related Disability and Cognitive Impairment(Week 8, 12 and 24)
- Modified Fatigue Impact Scale (MFIS) Score to Measure Fatigue at Week 8, 12 and 24(Week 8, 12 and 24)
- Fatigue Severity Scale (FSS) Score to Measure Fatigue by at Week 8, 12 and 24(Week 8, 12 and 24)
- Long Term Potentiation Measured by Transcranial Magnetic Stimulation (TMS)(Baseline (0 minute) and Post-Baseline (15 minutes) at Week 8)
- Number of Treated Participants With Immune-metabolic Response of Lymphocytes(Baseline, Week 8 and 12)