LiO-AD: Lithium Orotate in Alzheimers Disease Feasibility, Biomarker Engagement, and Clinical Response
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 40
- 主要终点
- Feasibility (Recruitment, Retention)
研究概览
简要总结
The goal of this clinical trial is to assess feasibility, safety, tolerability, and central nervous system target engagement of oral lithium orotate in adults with biomarker-confirmed early Alzheimer's disease. The main questions it aims to answer are:
- Can participants be recruited, retained, and remain adherent (target ≥80%) over 9 weeks of treatment, and what is the frequency and severity of adverse events?
- Does lithium orotate increase cerebrospinal fluid (CSF) lithium concentration from baseline to 9 weeks compared with placebo? Researchers will compare daily lithium orotate to matched placebo to see if lithium orotate demonstrates acceptable feasibility, safety, and tolerability and engages the central nervous system target (CSF lithium).
Participants will:
- Be randomized in a double-blind manner to receive lithium orotate or placebo for 9 weeks, with titration from week 1: 240 mg/day (10mg elemental lithium) to week 2: 480 mg/day (20mg elemental lithium) and week 3: 720 mg/day (30mg elemental lithium) if tolerated; dose reductions are permitted for side effects.
- Attend study visits for safety monitoring, adherence support (caregiver pill logs/diaries), and review of concomitant medications and adverse events.
- Provide blood samples and undergo lumbar punctures at baseline and post-treatment to measure CSF and serum lithium and Alzheimer's-related biomarkers; complete brief cognitive testing and neuropsychiatric symptom assessments.
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
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of Alzheimer's disease confirmed by biomarkers (imaging or biofluid evidence of amyloid-beta and tau pathology)
- •Mild stage of Alzheimer's disease: Clinical Dementia Rating (CDR) ≤ 1 or Quick Dementia Rating System (QDRS) ≤ 8
- •Medically stable and able to attend study visits and complete study procedures
- •On stable doses of any psychotropic medications for at least 4 weeks before the baseline visit
- •Not currently receiving anti-amyloid monoclonal antibody therapy
排除标准
- •New or unstable neurological disorder or unstable psychiatric illness that could affect safety or study results
- •Clinically significant kidney or thyroid problems that pose safety concerns, or abnormal safety labs judged to be related to study drug and requiring discontinuation
- •Use of thiazide diuretics during the dosing period (unless stopped at least 4 weeks before baseline)
- •Chronic daily use of non-aspirin NSAIDs (including COX-2 inhibitors); short courses require study team approval and may require temporary study drug hold and safety labs before resuming
- •Starting excluded therapies during the active treatment period (e.g., anti-amyloid monoclonal antibody treatment)
- •Noncompliance with essential study procedures that would prevent collection of primary safety or feasibility endpoints (e.g., repeated missed visits or refusal of critical labs)
研究组 & 干预措施
Matched placebo
干预措施: Matched Placebo (Capsules) (Drug)
Lithium orotate
干预措施: Lithium orotate (Drug)
结局指标
主要结局
Feasibility (Recruitment, Retention)
时间窗: Baseline up to Week 9
Proportion of eligible participants enrolled; proportion completing Week 9 procedures;
Feasibility (Visit Completion)
时间窗: Baseline up to Week 9
Proportion of scheduled visits completed
Feasibility (Adherence)
时间窗: Baseline up to Week 9
Medication adherence defined as percent of prescribed doses taken (target ≥80%)
Safety (Frequency of Adverse Events)
时间窗: Baseline up to Week 11 (includes Safety Follow-up)
Frequency of adverse events collected at each visit
Safety (Adverse Events Relatedness)
时间窗: Baseline through Week 11 (includes Safety Follow-up)
Relatedness of adverse event to intervention as determined by study physician (definitely related, possibly related, not related)
Safety (Adverse Events Severity)
时间窗: Baseline through Week 11 (includes Safety Follow-up)
Severity of adverse events as judged by study physician (mild, moderate, severe)
Safety (Renal function)
时间窗: Baseline through Week 11 (includes Safety Follow-up)
Renal function will be assessed by measuring creatinine levels in mg/dL
Safety (Thyroid functioning)
时间窗: Baseline through Week 11 (includes Safety Follow-up)
Thyroid functioning with be measured using thyroid stimulating hormone measured in mclU/mL
Tolerability (Dose Modifications)
时间窗: Baseline up to Week 9
Rates of dose reductions
Tolerability (Discontinuations)
时间窗: Baseline to Week 9
Rates of discontinuation
次要结局
- Central Nervous System Target Engagement (CSF Lithium Change)(Baseline up to Week 9)
- Change in neurofilament light chain (NfL)(Baseline up to Week 9)
- Neuropsychiatric Symptoms (NPI-Q)(Baseline up to Week 9)
- Delayed Recall(Baseline up to Week 9)