Repurposing Lithium as a Disease-modifying Therapy in Parkinson's Disease: A Randomized Controlled Trial
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Peripheral blood mononuclear cell (PBMC) nuclear receptor-related 1 protein (Nurr1) mRNA expression
研究概览
简要总结
This study will examine the effects of lithium 20mg/day compared to placebo on MRI and blood-based biomarkers among 20 early-stage Parkinson's disease patients.
详细描述
In observational studies, small daily doses of lithium have been associated with a 77% reduced risk of developing Parkinson's disease (PD). In addition, lithium therapy has been effective in preventing neuronal death and behavioral symptoms in several PD animal models. Recently, our group has shown 24-weeks of low-dose lithium therapy in PD to improve both MRI and blood-based biomarkers implying that lithium may be slowing the progression of the disease. However, these findings stem from only three of four patients receiving MRIs. A larger study will be required to determine if these promising results can be replicated. The proposed study will enroll 20 additional PD patients who will be randomly assigned to receive either lithium 20mg/day or identically-appearing placebo capsules for 24 weeks. This will be a double-blind study meaning that neither the patients nor the study team will know to which therapy patients have been assigned. Positive results from this study will support further research on lithium that could eventually support lithium as a disease-modifying therapy for PD that could improve patients' long-term prognoses.
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
- 40 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Have PD for <4 years diagnosed by a movement disorder specialist. Have normal thyroid and renal function at the screening visit. Have no previous exposure to lithium therapy. Have no history of brain surgery. Have no hx of brain imaging findings suggesting another neurological condition besides PD.
- •Have no use of tobacco or THC products for >1 year. Have stable PD medications for >30 days without current need for adjustments in the investigator's opinion.
- •Have stable psychiatric and diuretic medications for >60 days with no anticipated need for changes for at least 24 weeks.
- •Have no active medical or psychiatric condition that may interfere with study procedures in the investigator's opinion.
排除标准
- •Have PD for >4 years or does not have PD. Have abnormal normal thyroid and renal function at the screening visit. Have previous exposure to lithium therapy. Have history of brain surgery. Have hx of brain imaging findings suggesting another neurological condition besides PD.
- •Have use of tobacco or THC products within the past year. Have PD medication adjustments within 30 days or needs PD medication adjustments in the investigator's opinion.
- •Have psychiatric or diuretic medication adjustments within the last 60 days or is anticipated to need changes over next 24 weeks.
- •Have active medical or psychiatric condition that may interfere with study procedures in the investigator's opinion.
研究组 & 干预措施
Placebo
Identical capsules filled with cellulose: 10mg, 2x/day
干预措施: Placebo (Other)
Lithium
Lithium: 10mg, 2x/day
干预措施: Lithium (Dietary Supplement)
结局指标
主要结局
Peripheral blood mononuclear cell (PBMC) nuclear receptor-related 1 protein (Nurr1) mRNA expression
时间窗: Change from baseline (BL) to 24 week
PBMC Nurr1 mRNA expression using Taqman PCR.
MRI-derived free water (FW) levels.
时间窗: Change from baseline (BL) to 24 week
FW in the posterior substantia nigra (pSN), dorsomedial nucleus of the thalamus (DMN-T) and the nucleus basalts of Meynert (nbM).
Serum neurofilament light chain (NfL)
时间窗: Change from baseline (BL) to 24 week
Serum NfL assessed using SIMOA platform by Quanterix (Lexington, MA)
次要结局
- PBMC pS9/total glycogen synthase kinase-3B (GSK-3B) ratio(Change from baseline (BL) to 24 week)
- PBMC pThr308 and pS473/total protein kinase B (Akt) ratios(Change from baseline (BL) to 24 week)
- Parkinson's Anxiety Scale(Change from baseline (BL) to 24 week)
- Fatigue Severity Scale(Change from baseline (BL) to 24 week)
- PBMC superoxide dismutase type-1 (SOD-1) mRNA expression(Change from baseline (BL) to 24 week)
- Insomnia Severity Index(Change from baseline (BL) to 24 week)
- Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III (Motor Examination)(Change from baseline (BL) to 24 week)
- Levodopa equivalent daily dose (LEDD)(Change from baseline (BL) to 24 week)
- Serum interleukin-6(Change from baseline (BL) to 24 week)
- Geriatric Depression Scale-15(Change from baseline (BL) to 24 week)
- Serum glial fibrillary acidic protein (GFAP)(Change from baseline (BL) to 24 week)
- Montreal Cognitive Assessment (MoCA)(Change from baseline (BL) to 24 week)
- Parkinson's Disease Questionnaire-8(Change from baseline (BL) to 24 week)
研究者
Thomas Guttuso
Professor of Neurology
State University of New York at Buffalo