Allopregnanolone as a Regenerative Treatment for Parkinson's Disease: An Open-label, Pilot Clinical Trial
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Study completion
研究概览
简要总结
The goal of this open-label, pilot clinical trial is to test allopregnanolone as a regenerative treatment in patients with Parkinson's disease (PD). The main questions this study aims to answer are:
- Is a large-scale clinical trial testing how well it works in patients with PD feasible?
- Is allopregnanolone safe and well-tolerated in patients with PD.
- Can we see any signals of changes in imaging and clinical scales?
Participants will receive a weekly infusion in their vein of allopregnanolone for a total of 12 weeks. There is no placebo so everyone receives allopregnanolone and "Open-label" means the study is not blinded so both the participant and investigators know the assigned treatment.
详细描述
This is an open-label, pilot clinical trial of allopregnanolone (Allo) as a regenerative treatment for Parkinson's disease. A total of 10 study participants will receive weekly infusions of Allo for 12 weeks. Participants will be male and female, age 40-80 years with a history of idiopathic, sporadic PD who have a Hoehn & Yahr stage 1-4. Allo is a potent neuroregenerative agent that promotes proliferation of human neural stem cells and has the potential to function as a regenerative therapeutic to restore motor function in persons with PD. Results from several preclinical studies in rodent models of PD confirm improved motor function after Allo treatment.
Primary Objective: To assess the feasibility of a large-scale trial to determine the efficacy of weekly infusions of Allo in in patients with Idiopathic sporadic PD.
Secondary Objectives: To evaluate the safety and tolerability of weekly infusions of Allo in participants with idiopathic sporadic PD, and assess single-dose pharmacokinetics of allopregnanolone.
Tertiary / Exploratory Objectives: To assess efficacy signals of weekly infusions of Allo in participants with idiopathic sporadic PD.
- Determine target engagement of Allo using dopamine transporter (DaT) imaging and magnetic resonance imaging (MRI).
- Evaluate effect of Allo on motor function tests.
- Evaluate the effect of Allo on cognitive function tests and clinical ratings.
- Compare response to Allo administration between APOE4 carriers and non-carriers.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 40 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •History of Idiopathic sporadic Parkinson disease
- •Hoehn & Yahr stage 1-4
- •Have been on stable doses of all anti-Parkinson's medications for 30 days prior to screening
- •Provision of signed and dated informed consent form
排除标准
- •Evidence of Parkinsonian syndrome.
- •Any conditions that would contraindicate MRI studies.
- •Undergone deep brain stimulation (DBS) surgery as treatment for PD.
- •Iodine allergy, known serious hypersensitivity to ioflupane I-123, or other inability to undergo DaTscan.
- •Clinically significant abnormal laboratory value and/or clinically significant unstable medical or psychiatric illness.
- •History within the last 5 years of a primary or recurrent malignant disease, with the exception of resected cutaneous squamous cell carcinoma in situ, basal cell carcinoma, cervical carcinoma in situ, or prostate cancer in situ with a post-treatment prostatic-specific antigen within normal range.
- •Serious or unstable illnesses including cardiovascular, hepatic, renal, gastroenterologic, respiratory, endocrinologic, neurologic (other than PD), psychiatric, immunologic, or hematologic disease, and any other conditions that, in the investigator's opinion, could interfere with the safety and efficacy analyses in this study.
- •History of chronic alcohol or substance abuse/dependence within the past 3 years.
- •Current use of benzodiazepines, anticonvulsants, antipsychotics, or other drugs that might interact with the gamma-aminobutyric acid-A (GABA-A) receptor complex; use of calcium-channel blockers (e.g., amlodipine); use of dietary supplements containing Pregnenolone.
- •Treatment with another investigational drug within 3 months of screening.
研究组 & 干预措施
Allo APOE4 carriers
Group of 5 participants who are carriers of the APOE4 gene and will receive allopregnanolone 4mg administered weekly via a 30-min IV infusion for a duration of 12 weeks.
干预措施: Allopregnanolone (Drug)
Allo APOE4 none-carriers
Group of 5 participants who are none-carriers of the APOE4 gene and will receive allopregnanolone 4mg administered weekly via a 30-min IV infusion for a duration of 12 weeks.
干预措施: Allopregnanolone (Drug)
结局指标
主要结局
Study completion
时间窗: Week 13
Proportion of participant progression to study completion.
次要结局
- Infusion Reactions(Weekly from Week 1 to Week 16)
- Pharmacokinetics: Area under the plasma concentration versus time curve (AUC)(Week 1)
- Pharmacokinetics: Peak Plasma Concentration (Cmax)(Week 1)
- Adverse Events(Weekly from Baseline to Week 16)
- Pharmacokinetics: Half-life (t1/2)(Week 1)
- Pharmacokinetics: Time of peak concentration (tmax)(Week 1)
研究者
Roberta Brinton
Professor
University of Arizona