A Phase I Double Blind Study of Metformin Acting on Endogenous Neural Progenitor Cells in Children and Young Adults With Multiple Sclerosis
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Proportion of patients who completed each visit within the trial (retention)
研究概览
简要总结
A randomized multiple baseline feasibility trial where participants will start taking metformin at one of 3 randomly determined points (3-months, 6-months or 9 months) during the 12-month trial. All subjects will be on a daily dose of metformin for a minimum of 3 months and a maximum of 9 months.
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)
入排标准
- 年龄范围
- 10 Years 至 25 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with a history of MS with anterior visual pathway involvement and longer than 6 months after presentation with ON or an acute demyelinating event/relapse
- •Age 10 year to 25 years and 11 months
- •Latency delay > 115 milliseconds on baseline full-field transient pattern reversal VEP in at least one eye (electrophysiological evidence of demyelination) or > 10 milliseconds difference between eyes, or Retinal Nerve Fiber Layer (RNFL) thickness on OCT of < 90 µm in at least one eye or an inter-eye difference in the RNFL of 10 µm or more
- •Retinal Nerve Fiber Layer (RNFL) Thickness on baseline OCT ≥60 µm
- •If on an MS disease-modifying therapy, no changes in the therapeutic agent or dosing in the 6 months prior to study initiation
- •No significant renal or liver abnormalities
- •Expanded Disability Status Scale (EDSS) 0-6.0 (inclusive)
- •Has either English as his or her native language or English comprehension needed to complete the neuropsychological testing
- •Meet criteria for adequate organ function requirements as described below:
- •Adequate renal function defined as:
- •Creatinine clearance or radioisotope glomerular filtration rate (GFR) > 70 mL/min/1.73 m2 or serum creatinine based on age/gender as follows:
- •Range Serum Creatinine Level (µmol/L): Age 5 to <12 years (male)=25-50, Age 5 to <12 years (female)=25-50; Age 12 to <15 years (male)=37-67, Age 12 to <15 years (female)=37-67; Age 15 to <19 years (male)=51-89, Age 15 to <19 years (female)=40-69; Age ≥19 years (male)=58-110; Age ≥19 years (female)=46-92
- •Adequate liver function defined as:
- •Total bilirubin < 1.5 x upper limit of normal (ULN) for age SGOT (AST) or SGPT (ALT) < 1.5 x upper limit of normal (ULN) for age
排除标准
- •A history of retinal pathology (major ophthalmologic disease / concomitant ophthalmologic disorders)
- •Unstable and/or insulin-dependent (Type 1) diabetes, metabolic acidosis and/or lactic acidosis
- •History of unexplained hypoglycemia (<2.8 mmol/L)
- •Already on metformin
- •Concomitant use of any other putative remyelinating therapy as determined by the Principal/Qualified Investigator
- •Treatment for an acute attack with corticosteroids within 30 days prior to screening / relapse within 30 days prior to screening
- •Concomitant use of insulin
- •Concomitant use of any drugs that are listed to have drug-drug interactions with metformin (i.e. calcium channel blockers, diuretics, etc.) as determined by Principal/Qualified Investigator
- •Lactate levels > 1.5x upper limit of normal
- •Pregnancy
研究组 & 干预措施
Group A
Placebo for 3 months at dose of 500 mg/m2/day po (to be rounded) given in 1 or 2 divided doses for one week and if there are no side effects increased to 1000 mg/m2/day po given in 2 divided doses up to a maximum dose of 2000 mg/day.
Metformin for 9 months at dose of 500 mg/m2/day po (to be rounded) given in 1 or 2 divided doses for one week and if there are no side effects increased to 1000 mg/m2/day po given in 2 divided doses up to a maximum dose of 2000 mg/day.
干预措施: Metformin (Drug)
Group A
Placebo for 3 months at dose of 500 mg/m2/day po (to be rounded) given in 1 or 2 divided doses for one week and if there are no side effects increased to 1000 mg/m2/day po given in 2 divided doses up to a maximum dose of 2000 mg/day.
Metformin for 9 months at dose of 500 mg/m2/day po (to be rounded) given in 1 or 2 divided doses for one week and if there are no side effects increased to 1000 mg/m2/day po given in 2 divided doses up to a maximum dose of 2000 mg/day.
干预措施: Placebo (Other)
Group B
Placebo for 6 months at dose of 500 mg/m2/day po (to be rounded) given in 1 or 2 divided doses for one week and if there are no side effects increased to 1000 mg/m2/day po given in 2 divided doses up to a maximum dose of 2000 mg/day.
Metformin for 6 months at dose of 500 mg/m2/day po (to be rounded) given in 1 or 2 divided doses for one week and if there are no side effects increased to 1000 mg/m2/day po given in 2 divided doses up to a maximum dose of 2000 mg/day.
干预措施: Metformin (Drug)
Group B
Placebo for 6 months at dose of 500 mg/m2/day po (to be rounded) given in 1 or 2 divided doses for one week and if there are no side effects increased to 1000 mg/m2/day po given in 2 divided doses up to a maximum dose of 2000 mg/day.
Metformin for 6 months at dose of 500 mg/m2/day po (to be rounded) given in 1 or 2 divided doses for one week and if there are no side effects increased to 1000 mg/m2/day po given in 2 divided doses up to a maximum dose of 2000 mg/day.
干预措施: Placebo (Other)
Group C
Placebo for 9 months at dose of 500 mg/m2/day po (to be rounded) given in 1 or 2 divided doses for one week and if there are no side effects increased to 1000 mg/m2/day po given in 2 divided doses up to a maximum dose of 2000 mg/day.
Metformin for 3 months at dose of 500 mg/m2/day po (to be rounded) given in 1 or 2 divided doses for one week and if there are no side effects increased to 1000 mg/m2/day po given in 2 divided doses up to a maximum dose of 2000 mg/day.
干预措施: Metformin (Drug)
Group C
Placebo for 9 months at dose of 500 mg/m2/day po (to be rounded) given in 1 or 2 divided doses for one week and if there are no side effects increased to 1000 mg/m2/day po given in 2 divided doses up to a maximum dose of 2000 mg/day.
Metformin for 3 months at dose of 500 mg/m2/day po (to be rounded) given in 1 or 2 divided doses for one week and if there are no side effects increased to 1000 mg/m2/day po given in 2 divided doses up to a maximum dose of 2000 mg/day.
干预措施: Placebo (Other)
结局指标
主要结局
Proportion of patients who completed each visit within the trial (retention)
时间窗: 3 years
Number of patients with adverse events (safety and tolerability)
时间窗: 3 years
Proportion of patients who completed each of the outcome measures at the appropriate time points (adherence with outcome measures)
时间窗: 3 years
Number of patients enrolled in the study compared to the number of patients who were able to complete study measures (tolerability with outcome measures)
时间窗: 3 years
Number of patients who were approached to participate, declined participation and consented to participate (recruitment)
时间窗: 3 years
次要结局
- Optical Coherence Tomography (OCT) - Retinal Nerve Fiber Layer Thickness(3 years)
- Optical Coherence Tomography (OCT) - Optic Nerve Head Volume(3 years)
- Visual Evoked Potentials (VEP) - p100(3 years)
- Optical Coherence Tomography (OCT) - Ganglion Cell Inner Plexiform Layer Thickness(3 years)
研究者
E. Ann Yeh
Senior Associate Scientist, Division of Neuroscience and Mental Health, SickKids Research Institute
The Hospital for Sick Children