Safety and Efficacy of Allopregnanolone (Allo) as a Regenerative Therapeutic for Alzheimer's Disease: Multicenter, Double-Blind, Randomized, Placebo-Controlled, Phase 2 Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 100
- 试验地点
- 9
- 主要终点
- Hippocampal volume
研究概览
简要总结
A phase 2, double-blind, randomized, placebo-controlled clinical trial to evaluate the safety and efficacy of Allopregnanolone as a regenerative therapeutic for Alzheimer's disease.
详细描述
This is a proof-of-concept phase 2 clinical trial to investigate the long-term safety and efficacy of Allo to function as a regenerative therapeutic to restore structural integrity and cognitive function of the brain in participants with mild Alzheimer's disease (AD) dementia. Study participants will be male and female, diagnosed with probable AD, Mini-Mental State Exam (MMSE) 20 to 26, ages 55 to 80 years old.
After a 2-4-week screening period, participants will be randomized to 4 mg Allo (administered intravenously over 30 minutes, once per week, in clinic) or matching placebo, 1:1 allocation, for a period of 6 months. After 6 months, all participants in the placebo group will be crossed-over to receive Allo for the remainder of the study (3 month open-label phase). Brain imaging to evaluate the primary endpoint will be conducted at baseline, 3 and 6 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)
盲法说明
After 6 months participants and study personnel will be aware of the open label phase, but initial randomization will remain blind during the entire length of the study (placebo-controlled and open-label periods); that is, all participants and study personnel are blinded to each participant's randomization to initial treatment group.
入排标准
- 年龄范围
- 55 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Main Inclusion Criteria:
- •Men and postmenopausal women
- •Age 55 to 80 years old
- •Meets NIA-AA criteria for probable AD dementia
- •MMSE of 20-26
- •Plasma p-Tau217 positive
- •Geriatric Depression Scale short form (GDS-S) score of ≤ 6
- •No medical contraindications to participation
- •Capacity to provide informed consent at screening
排除标准
- •Dementia other than probable AD
- •Use of benzodiazepines, anticonvulsants, antipsychotics, or other drugs that might interact with the GABA-A receptor complex
- •History of stroke with a modified Hachinski Ischemic Scale score >4
- •History of seizure disorder, focal brain lesion, traumatic brain injury
- •History within the last 5 years of a primary or recurrent malignant disease
- •Unstable or clinically significant cardiovascular, kidney or liver disease
- •MRI indicative of any other significant abnormality, including but not limited to one or more significant ARIA-E or macro-hemorrhage findings, or multiple microhemorrhages (>8), or Fazekas score of 3; encephalomalacia, aneurysms, vascular malformations, subdural hematoma, or space occupying lesions
- •Any conditions that would contraindicate MRI studies.
- •No evidence of AD-like pattern of brain atrophy
研究组 & 干预措施
Control group
Placebo (normal saline) IV 30-minute infusion once per week for 6 months.
干预措施: Placebo (Other)
Allo group
Allopregnanolone 4mg IV 30-minute infusion once per week for 6 months.
干预措施: Allopregnanolone (Drug)
结局指标
主要结局
Hippocampal volume
时间窗: Baseline to 6 months
mm3
次要结局
- Cambridge Cognition's Paired Associates Learning Test(Baseline to 6 months)
- Cambridge Neuropsychological Test Automated Battery (CANTAB)(Baseline to 6 months)
- Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) 11(Baseline to 6 months)
- Alzheimer's Disease Cooperative Study (ADCS) Instrumental Activities of Daily (iADL) Living (iADL)(Baseline to 6 months)
- Safety and tolerability(Baseline to 6 months)
研究者
Roberta Brinton
Director, Center for Innovation in Brain Science; Professor, Departments of Pharmacology and Neurology
University of Arizona