Multicenter, Randomized, Double Blind, Placebo-Controlled Phase 2a Study, to Evaluate Safety, Tolerability and Pharmacokinetics of Resveratrol (JOTROLTM) in Parkinson's Disease
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 30
- 主要终点
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
研究概览
简要总结
This is an exploratory phase 2a study to investigate two doses of resveratrol (JotrolTM) vs placebo in individuals diagnosed with Parkinson's Disease (PD). Participants (n=30) will be randomized 1:1:1 into 3 groups and will receive oral JotrolTM vs placebo. Study drug will be titrated to reach a final maximal dose per group and will be administered orally once daily (QD) for 3 months. The study will primarily evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics (PK/PD) of JotrolTM.
详细描述
Core Study. JotrolTM in subjects with PD is a 3-month treatment (Core Study). A total of 30 subjects will be randomized 1:1:1 across JotrolTM, 200mg or 400mg versus placebo.
Biomarker Sub-study (Optional). There will be an additional sub-study, including cerebrospinal fluid (CSF) biomarkers assessments. Participation in this sub study is optional and will require specific consent that will not affect enrollment or treatment in the Core Study.
Number of Centers: Approximately 3 centers US-Wide Duration of Treatment: Participants will take the study drug (JotrolTM or matching placebo) orally, QD, for 3 months. Participants will be in the study for a total period of 4-5 months.
Duration of Study: Enrollment will be (competitive) open for 1 year and total study duration is 2 years.
Screening period: Consent and enrollment will take 4 weeks to determine eligibility and stabilize all participants on the standard of care (SOC).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 55 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Capable of providing informed consent (IC) and complying with study procedures
- •Stable on Levodopa and/or DA agonists for at least 4 weeks before enrollment
- •Clinical diagnosis of PD according to UK Brain Bank criteria and/or PD with Dementia (PDD) by MDS criteria (53-55).
- •Hohn and Yahr stage 2 and 3
- •Age of 55-85 years, medically stable
- •English Fluency
排除标准
- •Known PD-linked gene mutations e.g. PINK-1, DJ-1, parkin, LRRK2 etc.
- •Clinical signs indicating syndromes or disorders other than PD including, Alzheimer's Disease (AD), corticobasal degeneration (CBD), supranuclear gaze palsy, multiple system atrophy (MSA), chronic traumatic encephalopathy (CTE), frontal dementia, history of stroke, head injury or encephalitis, cerebellar signs, early severe autonomic involvement
- •Any psychiatric diagnosis or symptoms, (e.g., hallucinations and suicidality, major depression, or delusions) that could interfere with study procedures
- •Medical history of liver or pancreatic disease, GI, ulcers and Chron's disease, kidney, or blood problems. Any other clinically significant abnormalities in physical examination, vital signs, laboratory tests, or ECG at Screening or Baseline. Any other medical conditions (e.g., cardiac, respiratory, GI, renal disease) which are not adequately controlled, or which in the opinion of the investigator(s) could affect the subject's safety or interfere with the study assessments and are below grade 3 criteria as outlined in table
- •Enrolled as an active participant in another clinical study
- •Anti-coagulant medications, including Coumadin, heparin, enoxaparin, fondaparinux etc.
- •Any immunological disease which is not adequately controlled, or which requires treatment with immunoglobulins, systemic monoclonal antibodies (or derivatives of monoclonal antibodies), systemic immunosuppressant's, or plasmapheresis during the
- •Geriatric Depression Scale (GDS) score greater than or equal to 8 at Screening.
- •Answer "yes" to C-SSRS suicidal ideation Type 4 or 5, or any suicidal behavior assessment within 6 months before Screening, at Screening, or at the Baseline Visit, or has been hospitalized or treated for suicidal behavior in the past 5 years before Screening.
- •Planned surgery which requires general anesthesia that would take place during the study.
- •Severe visual or hearing impairment that would prevent the subject from performing psychometric tests accurately.
- •Women of Childbearing Potential (WCBP) or lactating.
- •Must not be on any nutritional or medicinal supplements at least 6 weeks prior to enrollment.
研究组 & 干预措施
200mg JotrolTM
In the first month, study drug will be titrated in multiple ascending doses. Participants will receive a single daily dose of 100mg JotrolTM in Week 1, and this dose will be escalated to 200mg at Week 2. If no Treatment Emergent Adverse Event (TEAE) is observed, participants will continue treatment with 200mg until week-12.
干预措施: Trans-Resveratrol (Drug)
400mg JotrolTM
In the first month, study drug will be titrated in multiple ascending doses. Participants will receive a single daily dose of 100mg JotrolTM in week-1, and this dose will increase to 200mg JotrolTM at week-2, and 300mg at week-3 and 400mg at Week 4. If no TEAEs are observed, participants will continue 400mg JotrolTM through Week 12. If any TEAE is observed during the titration period, participants will receive the prior (reduced) dose and continue the study until week-12. If the TEAE recurs in the same patient with a lower dose, the participant will be withdrawn from the study.
干预措施: Trans-Resveratrol (Drug)
Placebo
Participants will resume taking 4 placebo capsules once a day from Week 1 through 12
干预措施: Trans-Resveratrol (Drug)
结局指标
主要结局
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
时间窗: 12 weeks
Evaluate the safety and tolerability of JotrolTM in individuals diagnosed with PD via Adverse Events (AEs) and Treatment Emergent AEs (TEAEs)
Incidence of abnormal Electrocardiogram (ECG) findings [Safety and Tolerability])
时间窗: Change from Baseline to Week-12
Evaluate the safety and tolerability of JotrolTM in individuals diagnosed with PD via Electrocardiograms (ECG). ECGs with a QTc ≥500 ms and/or an increase of QTc ≥60 ms from baseline.
Determination of Jotrol's safe and tolerable dose in plasma [Safety and Tolerability]
时间窗: Between 5 to 12 weeks
Evaluate the PK of JotrolTM via measurement of its maximum concentration (Cmax) in plasma validated by the Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) method
Determination of Jotrol's safe and tolerable dose in Cerebral Spinal Fluid (CSF) [Safety and Tolerability]
时间窗: Between 5 to 12 weeks
Evaluate the PK of JotrolTM via measurement of its maximum concentration (Cmax) in CSF validated by the Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) method
次要结局
- Energy metabolism via blood levels of ATP(Change from Baseline to Week-12)
- Plasma biomarker analysis for the inflammatory profile(Change from Baseline to Week-12)
- Cerebral Spinal Fluid (CSF) biomarker analysis for the inflammatory profile(Change from Baseline to Week-12)
研究者
Fernando Pagan MD
Director of Movement Disorders Program
Georgetown University