A Proof of Concept Trial of a Sirtuin-NAD Activator in Alzheimer's Disease

Trial tests a new drug for Alzheimer's by checking if it reaches the brain.

NCT: NCT05040321 · Status: ACTIVE NOT RECRUITING · Phase: Phase 2 · Sponsor: Brigham and Women's Hospital · Started: 2021-12-01 · Est. Completion: 2026-04-30

Plain English Summary

Sirtuin-NAD Activator in Alzheimer's Disease is a Phase 2 clinical trial sponsored by Brigham and Women's Hospital studying Alzheimer's Disease (Incl Subtypes), Dementia. This trial tests a new drug called MIB-626 to see if it can enter the brain and affect the body's energy pathways related to aging. It is for individuals aged 55-85 diagnosed with Alzheimer's disease who show signs of the disease in their spinal fluid. Participants will take either the study drug or a placebo daily for 90 days and undergo regular tests, including blood draws and brain scans. Alternatives include currently approved Alzheimer's medications like cholinesterase inhibitors and memantine, which manage symptoms but do not cure the disease. The trial aims to enroll 22 participants.

Official Summary

The primary objectives are to: 1. To determine whether MIB-626, after its daily oral administration, penetrates the blood-brain barrier in humans by measuring the cerebrospinal fluid (CSF) concentrations of MIB-626 and its key metabolites, nicotinamide (NAM), NR, 2-PY, and MeNAM at baseline and on day 90 at steady state. 2. To evaluate whether oral MIB-626 administration engages the sirtuin-NAD pathway by determining the abundance of NAD (a SIRT1 substrate) in the brain using ultra-high field 7T magnetic resonance spectroscopy and in peripheral blood mononuclear cells using a validated LC-MS/MS assay. 3. To determine whether MIB-626 alters the circulating biomarkers of aging that the geroscience experts have recommended (HbA1C, IGF1, T3, IL6, TNF, and urinary F2-isoprostane).

Who Can Participate

Here is what you need to know about eligibility for this trial. You can join if you are between 55 and 85 years old and have been diagnosed with Alzheimer's disease. You must have specific evidence of Alzheimer's pathology in your spinal fluid and a mild to moderate cognitive impairment. You cannot join if you have other significant neurological diseases, certain brain imaging findings, a recent history of substance abuse, or specific psychiatric disorders. This trial is studying Alzheimer's Disease (Incl Subtypes), Dementia, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures how much of the study drug gets into the brain's fluid, which helps determine if the drug is reaching its target. The specific primary outcome measures are: change in CSF concentrations of MIB-626 (90 days). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial is important because it explores a new approach to treating Alzheimer's by targeting cellular aging processes, potentially filling a gap in current treatments that primarily manage symptoms Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Alzheimer's Disease (Incl Subtypes), Dementia, where improved treatment options are needed.

Investor Insight

This early-phase trial signals potential for a novel therapeutic approach in the large Alzheimer's market, though approval probability is low at this stage. Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor if this trial is a good fit for you, especially regarding the spinal tap procedure and potential side effects. Participation involves daily medication (drug or placebo) for 90 days, regular clinic visits, blood tests, cognitive assessments, and possibly brain imaging. You will need a reliable study partner to help with appointments and report on your daily functioning. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

Interventions

Primary Outcomes

Secondary Outcomes

Full Eligibility Criteria

Inclusion Criteria:

1. A man or a woman between the ages of 55 and 85 years (inclusive)
2. Meets National Institute on Aging-Alzheimer's Association (NIA-AA) clinical diagnostic criteria for AD dementia
3. Has evidence of AD pathological process by a positive amyloid assessment with cerebrospinal fluid (CSF) Aβ42
4. Has a Clinical Dementia Rating (CDR) global score of 0.5 or 1
5. Has a Mini-Mental State Exam (MMSE) Score of 18 to 26 (inclusive)
6. Has a 15-item Geriatric Depression Scale (GDS) score of \< 6
7. Impaired memory performance below education adjusted cut-off score on the Logical Memory II subscale delayed paragraph recall (LM-IIa) of the Wechsler Memory Scale-Revised (WMS-R) (≥16 years: ≤8; 8-15 years: ≤4; 0-7 years: ≤2)
8. May take Food and Drug Administration (FDA) approved medications for the treatment of AD dementia (cholinesterase inhibitors and/or memantine), but if taking such medications, they must be stable for at least 8 weeks before screening
9. Has adequate visual and auditory acuity to participate in neuropsychological testing and other study assessments
10. Has the availability of an informant (study partner) who has regular contact with the participant and knows him/her well
11. Is willing and able to participate in all assessments in English
12. Is capable of providing written informed consent

Exclusion Criteria:

Subjects may not be enrolled if:

1. Neurologic diseases: Any significant neurologic disease other than AD that can lead to cognitive impairment, such as Parkinson's disease, vascular dementia, dementia with Lewy bodies, frontotemporal dementia, Huntington's disease, normal pressure hydrocephalus, corticobasal syndrome, brain tumor, seizure disorder, subdural hematoma (within the last 1 year), multiple sclerosis, or history of significant head trauma (e.g. loss of consciousness for 30 minutes or more) followed by persistent neurologic deficits or known structural brain abnormalities.
2. Neuroimaging: Baseline or prior magnetic resonance imaging (MRI) scans with evidence of cortical stroke or hemorrhage, strategically located lacunar stroke (ex: left thalamus), or severe small vessel ischemic disease.
3. History of alcohol or substance use disorder or dependence (DSM V criteria) within the last 2 years.
4. Psychiatric disorder: Major depressive disorder (within the last 1 year), bipolar disorder, schizophrenia (DSM V criteria), or current major psychotic symptoms or behavioral problems that could interfere with study procedures.
5. Any significant systemic illness or unstable medical condition, which could obfuscate cognitive aging or neurodegenerative trajectories or affect valid cognitive and self-report measurements.
6. Excluded medications: Niacin or dietary supplements containing nicotinamide mononucleotide (NMN) or nicotinamide riboside (NR); antipsychotic medications, antidepressant medications with anticholinergic side effects. Washout from psychoactive medications for at least 8 weeks before screening.
7. Current use of anticoagulants; significant back or spine disease that would make a lumbar puncture difficult or unsafe as determined by a clinician.
8. Other laboratory abnormalities: Has AST or ALT \> 3 times the upper limit of normal; serum creatinine \> 2.0 mg/d; HbA1C \> 8.5%
9. Participation in an investigational trial to evaluate pharmaceuticals or biologics within the past 3 months or 5 half-lives, whichever is shorter
10. Other medical conditions which, in the opinion of the investigator, would jeopardize safety or impact the validity of the study results.

Trial Locations

Frequently Asked Questions

What is clinical trial NCT05040321?

NCT05040321 is a Phase 2 INTERVENTIONAL study titled "Sirtuin-NAD Activator in Alzheimer's Disease." It is currently active, not recruiting and is sponsored by Brigham and Women's Hospital. The trial targets enrollment of 22 participants.

What conditions does NCT05040321 study?

This trial investigates treatments for Alzheimer's Disease (Incl Subtypes), Dementia. The primary condition under study is Alzheimer's Disease (Incl Subtypes).

What treatments are being tested in NCT05040321?

The interventions being studied include: MIB-626 (DRUG), Placebo (DRUG). Participants will be randomized to either receive MIB-626 or matching placebo. The proposed intervention - targets multiple contributors to the pathology of AD; MIB-626 improves mitochondrial function, bioenergetics, and insulin sensitivity, inhibits A beta accumulation by reducing its synthesis and increasing its clearance, reduces neuroinflammation, exerts neuronal protective effects, and promotes neuronal regeneration and connectivity in preclinical models.

What does Phase 2 mean for NCT05040321?

Phase 2 trials test whether the treatment works for the intended condition. They involve 100-300 patients and continue to evaluate safety while measuring effectiveness.

What is the current status of NCT05040321?

This trial is currently "Active, Not Recruiting." It started on 2021-12-01. The estimated completion date is 2026-04-30.

Who is sponsoring NCT05040321?

NCT05040321 is sponsored by Brigham and Women's Hospital. The sponsor is responsible for funding, designing, and overseeing the clinical trial.

How many people can participate in NCT05040321?

The trial aims to enroll 22 participants. The trial status is active, not recruiting.

How is NCT05040321 designed?

This is a interventional study, uses randomized allocation, follows a parallel design, employs quadruple masking. Masking means some participants and/or investigators do not know which treatment group a participant is in, which helps reduce bias.

What are the primary outcomes being measured in NCT05040321?

The primary outcome measures are: change in CSF concentrations of MIB-626 (90 days). These are the main endpoints researchers use to determine whether the treatment is effective.

Where is NCT05040321 being conducted?

This trial is being conducted at 1 site, including Boston, Massachusetts (United States).

Where can I find official information about NCT05040321?

The official record for NCT05040321 is available on ClinicalTrials.gov at https://clinicaltrials.gov/study/NCT05040321. This government database provides the most up-to-date and detailed information about the trial.

What is NCT05040321 testing in simple terms?

This trial tests a new drug called MIB-626 to see if it can enter the brain and affect the body's energy pathways related to aging. It is for individuals aged 55-85 diagnosed with Alzheimer's disease who show signs of the disease in their spinal fluid.

Why is this trial significant?

This trial is important because it explores a new approach to treating Alzheimer's by targeting cellular aging processes, potentially filling a gap in current treatments that primarily manage symptoms

What are the potential risks of participating in NCT05040321?

The most common risks are related to the procedures, such as discomfort or bruising from blood draws and potential headaches or back pain from spinal taps. Potential side effects of the study drug are not fully known but could include gastrointestinal issues, fatigue, or changes in mood. As this is a proof-of-concept trial, the long-term effects and efficacy are still under investigation. As with any clinical trial, participants are closely monitored and can withdraw at any time.

Should I consider participating in NCT05040321?

Ask your doctor if this trial is a good fit for you, especially regarding the spinal tap procedure and potential side effects. Participation involves daily medication (drug or placebo) for 90 days, regular clinic visits, blood tests, cognitive assessments, and possibly brain imaging. You will need a reliable study partner to help with appointments and report on your daily functioning. Always discuss clinical trial participation with your healthcare provider to determine if it is appropriate for your specific situation.

What does NCT05040321 signal from an investment perspective?

This early-phase trial signals potential for a novel therapeutic approach in the large Alzheimer's market, though approval probability is low at this stage. This is a Phase 2 trial, which is focused on confirming efficacy before larger pivotal studies.

What happens if the treatment in this trial doesn't work?

Participants will take either the study drug or a placebo daily for 90 days and undergo regular tests, including blood draws and brain scans. Participants in clinical trials always have the right to withdraw and pursue alternative treatments. The study team will help transition patients to other available options.

Related Conditions

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This analysis is AI-generated and does not constitute medical advice. Always consult your healthcare provider before making decisions about clinical trial participation.