Alzheimer s DiseasePhase 1/2LiO-ADNCT07459959
LiO-AD: Lithium Orotate in Alzheimers Disease Feasibility, Biomarker Engagement, and Clinical Response
A Phase 1/2 study testing Lithium orotate in people with Alzheimer s Disease, run by Johns Hopkins University.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Alzheimer s Disease
- What is being tested?
- Lithium orotate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- No sites listed yet
- Study dates
- 1 Dec 2026to 31 Aug 2029
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
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).
Read more
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.
- Conditions
- Alzheimer s Disease
- Being tested
- Lithium orotate, Matched Placebo (Capsules)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lithium orotateDrug
Lithium orotate (LiO) oral capsules, over-encapsulated to match placebo. 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 (note that 240mg LiO = ~10mg elemental Li)
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 adherence tools Safety monitoring at each visit with renal and thyroid laboratory assessments; The selected LiO dose (target 720 mg/day) reflects upper limit safely used as a supplement (30mg elemental Li).
Randomized, double-blind, placebo-controlled design with identical schedules across arms.
Matched Placebo (Capsules)Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| Lithium orotate | Experimental | Not described Receives: Drug: Lithium orotate |
| Matched placebo | Placebo comparator | Not described Receives: Drug: Matched Placebo (Capsules) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Feasibility (Recruitment, Retention)
Proportion of eligible participants enrolled; proportion completing Week 9 procedures;
Measured: Baseline up to Week 9
Feasibility (Visit Completion)
Proportion of scheduled visits completed
Measured: Baseline up to Week 9
Feasibility (Adherence)
Medication adherence defined as percent of prescribed doses taken (target ≥80%)
Measured: Baseline up to Week 9
Safety (Frequency of Adverse Events)
Frequency of adverse events collected at each visit
Measured: Baseline up to Week 11 (includes Safety Follow-up)
Safety (Adverse Events Relatedness)
Relatedness of adverse event to intervention as determined by study physician (definitely related, possibly related, not related)
Measured: Baseline through Week 11 (includes Safety Follow-up)
Safety (Adverse Events Severity)
Severity of adverse events as judged by study physician (mild, moderate, severe)
Measured: Baseline through Week 11 (includes Safety Follow-up)
Safety (Renal function)
Renal function will be assessed by measuring creatinine levels in mg/dL
Measured: Baseline through Week 11 (includes Safety Follow-up)
Safety (Thyroid functioning)
Thyroid functioning with be measured using thyroid stimulating hormone measured in mclU/mL
Measured: Baseline through Week 11 (includes Safety Follow-up)
Tolerability (Dose Modifications)
Rates of dose reductions
Measured: Baseline up to Week 9
Tolerability (Discontinuations)
Rates of discontinuation
Measured: Baseline to Week 9
Secondary outcomes (4)
Central Nervous System Target Engagement (CSF Lithium Change)
Change in cerebrospinal fluid (CSF) lithium concentration from baseline to post-treatment, comparing lithium orotate vs. placebo (mEq/L)
Measured: Baseline up to Week 9
Change in neurofilament light chain (NfL)
Change from baseline in CSF NfL measured in pg/mL
Measured: Baseline up to Week 9
Neuropsychiatric Symptoms (NPI-Q)
Change in Neuropsychiatric Inventory Questionnaire (NPI-Q) total score from baseline to post-treatment; between-group comparisons at Week 9. Scored 0-36 with a higher score representing more severe symptoms.
Measured: Baseline up to Week 9
Delayed Recall
Change in Hopkins Verbal Learning Test-Revised score from baseline to post-treatment; between-group comparisons at Week 9. Scored from 0-36 with a higher score representing better cognitive performance.
Measured: Baseline up to Week 9
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2026
- Study start1 Dec 2026 (estimated)
- Primary completion1 Jun 2029 (estimated)
- Study completion31 Aug 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer s DiseaseStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Responsible party
- Sponsor
- Investigators
- Christopher Morrow, MD, MHS, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07459959
- Sponsor's protocol ID
- IRB00540477
- Acronym
- LiO-AD
- Status last verified
- Oct 2026
- First submitted
- 4 Mar 2026
- Last updated
- 7 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- LiO-AD: Lithium Orotate in Alzheimers Disease Feasibility, Biomarker Engagement, and Clinical Response
- ClinicalTrials.gov ID
- NCT07459959
- Acronym / sponsor ID
- LiO-AD / IRB00540477
- Conditions
- Alzheimer s Disease
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Study start
- 1 Dec 2026 (estimated)
- Primary completion
- 1 Jun 2029 (estimated)
- Study completion
- 31 Aug 2029 (estimated)
- First posted
- 10 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Lithium orotate | Experimental | Drug: Lithium orotate |
| Matched placebo | Placebo comparator | Drug: Matched Placebo (Capsules) |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (6 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lithium orotateLithium orotate (LiO) oral capsules, over-encapsulated to match placebo. 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 (note that 240mg LiO = ~10mg elemental Li) 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 adherence tools Safety monitoring at each visit with renal and thyroid laboratory assessments; The selected LiO dose (target 720 mg/day) reflects upper limit safely used as a supplement (30mg elemental Li). Randomized, double-blind, placebo-controlled design with identical schedules across arms. | Drug | Lithium orotate |
| 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. | Drug | Matched placebo |
Primary outcome
Feasibility (Recruitment, Retention)
Time frame: Baseline up to Week 9
Proportion of eligible participants enrolled; proportion completing Week 9 procedures;
Feasibility (Visit Completion)
Time frame: Baseline up to Week 9
Proportion of scheduled visits completed
Feasibility (Adherence)
Time frame: Baseline up to Week 9
Medication adherence defined as percent of prescribed doses taken (target ≥80%)
Safety (Frequency of Adverse Events)
Time frame: Baseline up to Week 11 (includes Safety Follow-up)
Frequency of adverse events collected at each visit
Safety (Adverse Events Relatedness)
Time frame: 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)
Time frame: Baseline through Week 11 (includes Safety Follow-up)
Severity of adverse events as judged by study physician (mild, moderate, severe)
Safety (Renal function)
Time frame: Baseline through Week 11 (includes Safety Follow-up)
Renal function will be assessed by measuring creatinine levels in mg/dL
Safety (Thyroid functioning)
Time frame: Baseline through Week 11 (includes Safety Follow-up)
Thyroid functioning with be measured using thyroid stimulating hormone measured in mclU/mL
Tolerability (Dose Modifications)
Time frame: Baseline up to Week 9
Rates of dose reductions
Tolerability (Discontinuations)
Time frame: Baseline to Week 9
Rates of discontinuation
4 secondary outcomes
Central Nervous System Target Engagement (CSF Lithium Change)
Time frame: Baseline up to Week 9
Change in neurofilament light chain (NfL)
Time frame: Baseline up to Week 9
Neuropsychiatric Symptoms (NPI-Q)
Time frame: Baseline up to Week 9
Delayed Recall
Time frame: Baseline up to Week 9
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Oct 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Christopher Morrow, MD, MHS principal investigator
Johns Hopkins University
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Lithium orotate in people with Alzheimer s Disease, run by Johns Hopkins University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 7 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Christopher Morrow, MD, MHS (410-955-5147, cmorrow3@jh.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Feasibility (Recruitment, Retention) (time frame: Baseline up to Week 9). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Oct 2026.