NCT07459959

LiO-AD: Lithium Orotate in Alzheimers Disease Feasibility, Biomarker Engagement, and Clinical Response

• Status: Not Yet Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: Johns Hopkins University · Academic / Other
• Sex: All
• Age: —
• Healthy volunteers: Not accepted

Summary

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 240 mg/day (week 1) to 480 mg/day (week 2) and 720 mg/day (week 3) 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.

Conditions

• Alzheimer s Disease

Interventions

Type	Name	Description
DRUG	Lithium orotate	Lithium orotate (LiO) oral capsules, over-encapsulated to match placebo in appearance, weight, and packaging. Dosing uses a structured titration over 3 weeks followed by maintenance through week 9: Week 1: 240 mg/day Week 2: 480 mg/day Week 3: 720 mg/day (target dose), with option to down-titrate to 480 mg/day or 240 mg/day if side effects occur Key distinguishing features: Population: adults with biomarker-confirmed early Alzheimer's disease. Central nervous system target engagement assessed via change in CSF lithium from baseline to week 9, measured by lumbar puncture; serum lithium also collected for correlation. Feasibility and tolerability supported by caregiver-based adherence tools Safety monitoring at each visit with renal and thyroid laboratory assessments; The selected LiO dose (target 720 mg/day) reflects the upper limit of doses safely used as a supplement. Randomized, double-blind, placebo-controlled design with identical schedules and communications across arms.
DRUG	Matched Placebo (Capsules)	Matched placebo oral capsules, over-encapsulated to be indistinguishable from lithium orotate in appearance, weight, packaging, labeling, and dosing instructions. The dosing schedule mirrors the active arm to maintain blinding: Week 1: one capsule daily (matching 240 mg/day schedule) Week 2: two capsules daily (matching 480 mg/day schedule) Week 3 through Week 9: three capsules daily (matching 720 mg/day target), with option to maintain a lower capsule count if down-titration is required to mirror tolerability adjustments in the active arm Key distinguishing and blinding-maintenance features: Randomized, double-blind, placebo-controlled administration with identical visit schedules, counseling, adherence supports. Study staff, participants, caregivers, and outcome assessors remain blinded. Safety monitoring (including renal and thyroid labs) and adverse event assessments occur at the same frequency as the active arm without revealing assignment.

Timeline

• Start date: 2026-06-01
• Primary completion: 2029-06-01
• Completion: 2029-08-31
• First posted: 2026-03-10
• Last updated: 2026-03-10