A Phase II Trial of High-Dose Vitamin D Induction in Optic Neuritis (VitaDON 2)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Inter-eye (IED) ganglion cell layer thickness (GCL)
研究概览
简要总结
This is a phase II randomized double-blind placebo/standard of care trial to determine if rapidly inducing vitamin D sufficiency in patients with acute optic neuritis results in less damage/greater recovery at 12 months as measured by optical coherence tomography, visual evoked potentials, visual acuity and radiological measures. Our hypothesis, based on earlier observational studies, is that acute optic neuritis in the context of vitamin D sufficiency results in better visual outcomes compared to those that are not sufficient acutely, regardless of such interventions as steroid therapy.
详细描述
The present trial is based on the observation that vitamin D sufficiency appears to provide some degree of neuroprotection and/or repair in the context of an acute optic neuritis when followed over several months using optical coherence tomography measures. Based on these findings, this randomized double-blinded placebo/standard of care controlled trial has been designed to to see if rapidly inducing vitamin D sufficiency (defined in this trial as a serum 25(OH)D value => 80 nmol/L) results in relatively less reduction in neuroaxonal injury and/or improved recovery chronically (at month 12) versus those patients who do not achieve vitamin D sufficiency in the acute optic neuritis period. of Vitamin D. In this trial, 66 patients in total will be randomized to either "high-dose vitamin D induction" treatment group or the "placebo/followed by standard of care vitamin D" group and followed over 12 months.The primary measure of neuroaxonal integrity in this trial is optical coherence tomography outcomes including ganglion cell layer thickness, retinal nerve fiber layer thickness and macular volume. Other vision metrics and magnetic resonance imaging (MRI) measures will provide secondary outcome indicators of this as well.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Masked randomization and allocation, only data safety monitor will know allocation if adverse event requires unblinding
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Canadian residents
- •Patients must be between age 18 and 45 years
- •Patients must have a diagnosis of either a CIS or RRMS (according to McDonald criteria)
- •Patients must have an EDSS of 5.5 or less
- •Patients must demonstrate features of a first typical optic neuritis within 21 days of recruitment (or must initiate treatment by day 30)
- •Patients must have a baseline 25(OH)D < 80 nmol/L regardless of vitamin D3 supplementation
- •Patients must have no contraindications to high-dose vitamin D supplementation
- •Female patients must consent to use a reliable form of contraception (oral contraceptive pill, intrauterine device, barrier methods, abstinence) for the duration of the active treatment phase (first 90 days of where study drug provided) of the trial
- •Patients must provide written informed consent.
排除标准
- •Patients who have had a previous optic neuritis
- •Patients with evidence of a non-inflammatory cause of optic neuropathy
- •Patients with evidence of neuromyelitis optica spectrum disorder or "NMOSD" (i.e. bilateral optic neuritis, MRI evidence of longitudinally enhancing lesions involving the optic nerves (involving three or more segments of the optic nerve), and/or involving the optic chiasm, and optic tracts
- •Patients with a 25(OH)D > 80 nmol/L
研究组 & 干预措施
High-Dose Vitamin D Treatment Group
Patients in this arm will receive:
-5 days of high-dose oral vitamin D3 (50,000 IU daily x 5), followed by 85 days of moderate dose oral vitamin D3 (10,000 IU daily x 85 days)
干预措施: Vitamin D3 (Drug)
Placebo/Standard Vitamin D3 Group
Patients in this arm will receive Placebo/Standard of Care Vitamin D3:
-5 days of placebo, followed by 85 days of standard of care dose of oral vitamin D3 (4,000 IU daily x 85 days)
干预措施: Placebo/Standard of Care Vitamin D3 (Drug)
结局指标
主要结局
Inter-eye (IED) ganglion cell layer thickness (GCL)
时间窗: month 12
The difference between the unaffected and affected eye GCL thickness between treatment and placebo group
Proportion of patients with GCL IED <= 8 microns
时间窗: 12 months
The proportion of patients with unaffected and affected eye GCL thickness of \< = 8 microns between groups
次要结局
- Change in mean GCL IED between eyes over time(baseline to 12 months)
- Correlation between baseline mean multifocal VEP latency and month-12 GCL, GCL inter-eye difference, RNFL and inter-eye RNFL difference between treatment and placebo groups(12 months)
- Mean change high and low contrast visual acuity (LogMAR)(12 months)
- Change in mean GCL in affected eye over time(baseline to 12 months)
- Mean RNFL thickness(12 months)
- Change in mean retinal nerve fiber layer (RNFL) in affected eye over time(baseline to 12 months)
- Change in mean RNFL IED between eyes over time(baseline to 12 months)
- Inter-eye GCL thickness(12 months)
- Mean macular volume (MV)(12 months)
- Mean multifocal VEP (MfVEP) latency(1 month)
- Change in mean RNFL in affected eye over time(baseline to 12 months)
- Mean GCL thickness(12 months)
- Inter-eye RNFL thickness(12 months)
研究者
Jodie Burton MD, MSc, FRCPC
Assistant Professor
University of Calgary