Adrenocorticotropic Hormone (ACTH) Effects on Myelination in Subjects With MS
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Change in Myelin Water Fraction (MWF) Within New Enhancing Lesions Over the Course of 12 Months
研究概览
简要总结
The primary objective of this study is to determine if monthly pulse doses of a three-day course ACTH (H.P. Acthar®) is more effective at recovering myelin at 12 months, as measured by myelin water fraction (MWF), in new multiple sclerosis lesions as compared to one course of treatment.
The main secondary objective is to utilize every three month MWF measurements to determine the peak time of remyelination in new multiple sclerosis lesions when followed over the course of 12 months.
详细描述
This pilot study proposal is designed to perform a chronological measurement of MWF in new contrast-enhancing lesions in subjects treated with ACTH during an acute exacerbation of MS.
The initial course of ACTH (H.P. Acthar®) will be administered as recommended in the package insert, a subcutaneous daily dose of 80-120mg units daily for 2-3 weeks. However, as recommended in the package insert, the dosage may be individualized according to the medical condition of each subject. Therefore, the frequency and dose of the drug may be determined by considering the severity of the disease and the initial response of the subject. The typical dosing for an MS exacerbation is 80mg/day for 3-5 days and it is expected that this will be the initial dosing for the majority of thesubjects.
MS subjects enrolled in this study will be randomized into:
One Time Treatment: 80mg/day ACTH for 3-5 days (The dose could be adjusted based on the individual needs of the subjects up to 80-120mg units daily for 2-3 weeks.)
Monthly Treatments: 80mg/day ACTH for 3-5 days (The dose could be adjusted based on the individual needs of the the subjects up to 80-120mg units daily for 2-3 weeks.), followed by monthly 80 mg/day ACTH for 3 days for up to 12 months of treatment.
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
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Patients with RRMS or SPMS with new contrast-enhancing lesions who will start as part of their standard of care ACTH.
排除标准
- •Patients having received oral or IV corticosteroids within one month prior to initial scan demonstrating contrast enhancing lesion
- •Patients with known or new allergy to ACTH
- •Patients being treated with Natalizumab, Rituximab, and Cyclophosphamide
- •Patients unwilling to have serial MRI exams
- •Patients unable to undergo MRI imaging because of having an artificial heart valve, metal plate, pin, or other metallic objects in their body or is unable to complete all the MRI scans required for this study
- •Patients with acute or chronic renal disease in whom administration of gadolinium may pose risk of nephrogenic systemic fibrosis
- •Patients that are pregnant
- •Premenopausal woman not willing to use at least one form of contraception
- •Patients with a known history of diabetes mellitus
- •Patients with a known history of osteoporosis or bone density values in the osteoporosis range at screening
- •Progressive neurological disorder other than RRMS or SPMS
- •Clinically significant cardiovascular disease, including myocardial infarct within last 6 months, unstable ischemic heart disease, congestive heart failure, or angina
- •Subjects on chronic steroid therapy for treatment of MS or other systematic disease
- •Subject currently has a significant medical condition (other than MS) including the following: neurological, psychiatric, metabolic, hepatic, renal, hematological, pulmonary, cardiovascular (including uncontrolled hypertension), gastrointestinal, urological disorder, or central nervous system (CNS) infection that would pose a risk to the subject if they were to participate in the study or that might confound the results of the study
- •o Note: Active medical conditions that are minor or well-controlled are not exclusionary if, in the judgment of the Primary Investigator, they do not affect risk or the subject or the study results.
- •Subject is unable to cooperate with any study procedures, unlikely to adhere to the study procedures and keep appointments, in the opinion of the Investigator, or was planning to relocate during the study
研究组 & 干预措施
One Time Treatment
MS patients enrolled in this study will be randomized into:
Intervention for Group A: 80 units/day ACTH (H.P. Acthar®)for 3-5 days (The dose could be adjusted based on the individual needs of the patients up to 80-120 units daily for 2-3 weeks.)
干预措施: Adrenocorticotropic hormone (ACTH) gel (H.P. Acthar®) (Drug)
Monthly Treatments
Intervention for Group B: 80 units/day ACTH (H.P. Acthar®) for 3-5 days (The dose could be adjusted based on the individual needs of the patients up to 80-120 units daily for 2-3 weeks.), followed by monthly 80 units/day ACTH for 3 days for 12 months of treatment.
干预措施: Adrenocorticotropic hormone (ACTH) gel (H.P. Acthar®) (Drug)
结局指标
主要结局
Change in Myelin Water Fraction (MWF) Within New Enhancing Lesions Over the Course of 12 Months
时间窗: Baseline, 12 months
Primary outcome: The absolute change in lesion MWF (over our test-retest variability) between baseline and one year MRI's will be calculated and compared between treatment groups. Method to assess lesion MWF: FAST-T2 is a multi-compartment T2 relaxometry MRI technique wherein the contribution of water associated with myelin and other tissue compartments is differentiated using T2 decay curve analysis. The relative contribution of the myelin water with respect to total water is represented as MWF. A higher MWF within a lesion reflects higher myelin content within that lesion. For this analysis, MWF maps were reconstructed from FAST-T2 MRI data by using a multi-voxel nonlinear least-squares data-fitting algorithm with spatial smoothness constraints. MWF was calculated as the ratio of the myelin water signal to the total water signal within a voxel. Lesion MWF is an average of the voxels present within an individual lesion.
次要结局
- Change in T2 Lesion Volume(12 months)
- Physical Disability as Measured by EDSS(12 months)
- Cortical Volume(12 Months)
- Whole Brain Volume(12 months)
- Longitudinal Assessment of MWF(12 months)