Sirtuin-NAD Activator for Alzheimer's Disease

Overseen By Shalender Bhasin, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Brigham and Women's Hospital

Must be taking: Cholinesterase inhibitors, Memantine

Must not be taking: Niacin, Antipsychotics, Antidepressants

Disqualifiers: Parkinson's, Alcohol use, Major depression, others

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether MIB-626, a Sirtuin-NAD activator, can cross into the brain and affect pathways related to Alzheimer's disease. Researchers aim to determine if this drug influences brain chemicals and aging markers in the body. Participants will receive either MIB-626 or a placebo (a pill with no active drug) to compare effects. The trial suits those diagnosed with Alzheimer's who have regular contact with a caregiver to assist throughout the study. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I have to stop taking my current medications for the trial?

You may need to stop certain medications, like niacin, supplements with NMN or NR, antipsychotics, and some antidepressants, at least 8 weeks before the trial. However, you can continue taking stable doses of FDA-approved Alzheimer's medications like cholinesterase inhibitors or memantine.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that MIB-626 is generally safe for people. In earlier studies, participants who took MIB-626, similar to a compound called NMN, did not experience serious side effects. NMN is known to increase a substance called NAD, which might help with aging issues like brain damage and stress. The amount used in these studies was found to be safe. This trial will examine how MIB-626 affects the brain and aging, with previous research supporting its safety for participants. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Alzheimer's?

Unlike the standard Alzheimer's treatments that typically focus on symptom management, MIB-626 targets the root causes of the disease. This experimental drug acts on the sirtuin-NAD pathway, which is involved in cell health and aging, potentially slowing down or even reversing the damage in brain cells. Researchers are excited because this new mechanism of action could offer a more effective approach to treating Alzheimer's by addressing its underlying biological processes rather than just its symptoms.

What evidence suggests that MIB-626 might be an effective treatment for Alzheimer's?

Research has shown that MIB-626, a type of nicotinamide mononucleotide (NMN), might improve brain health by raising NAD+ levels. NAD+ is a molecule that helps repair cells and provide energy. Some studies suggest that NMN can help with issues like sleepiness and limb movement. NMN also seems to combat aging effects, such as damage from free radicals and nerve cell damage. Early results indicate that taking NMN increases NAD+ levels in the blood, which might help with age-related problems. In this trial, participants will receive either MIB-626 or a placebo to further investigate its effects on Alzheimer's disease. Although these findings are promising, more research is needed to confirm its effects on Alzheimer's disease specifically. ^{1 2 3 5 6}

Who Is on the Research Team?

Shalender Bhasin, MD

Principal Investigator

Brigham and Women's Hospital

Neha K Rupeja, MS

Principal Investigator

Brigham and Women's Hospital

Are You a Good Fit for This Trial?

This trial is for adults aged 55-85 with Alzheimer's Disease, scoring low on memory and mental state exams, not suffering from other cognitive impairments or unstable medical conditions. Participants must have a reliable informant and be able to consent and participate in English.

Inclusion Criteria

I am between 55 and 85 years old.

I have been diagnosed with Alzheimer's disease according to NIA-AA guidelines.

I have been on stable Alzheimer's medication for at least 8 weeks.

Exclusion Criteria

I do not have any major illnesses that could affect my thinking or memory tests.

I am currently using blood thinners and have back issues that may make a spinal tap risky.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive MIB-626 or placebo tablets twice daily for 90 days to evaluate penetration of the blood-brain barrier and engagement of the sirtuin-NAD pathway.

12 weeks

Regular visits for monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment, including changes in neuropsychiatric symptoms, cognition, and biomarkers.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• MIB-626
• Nicotinamide Mononucleotide
• Placebo

Trial Overview The study tests MIB-626, a daily oral drug thought to penetrate the brain barrier and activate the sirtuin-NAD pathway related to aging. Its effects are compared against a placebo by measuring substances in cerebrospinal fluid and blood.

How Is the Trial Designed?

Group I: MIB-626 Experimental Treatment 1 Intervention

Subjects will either take MIB-626 or placebo tablet twice a day for 90 days. For those who receive MIB-626, we plan on giving subjects 1000mg of the drug, twice a day for 90 days. MIB-626 will be in two 500mg tablets.

Group II: Placebo Tablet Placebo Group 1 Intervention

Subjects will be randomized to receive either the placebo or MIB-626 tablets twice a day orally.

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9735188/

The efficacy and safety of β-nicotinamide mononucleotide ... The trial found that only drowsiness and lower limb function in the afternoon NMN-treated group were significantly improved among the many trial ...

2. alzheimers.gov alzheimers.gov/clinical-trials/mib-626-alzheimers-disease

MIB-626 for Alzheimer's Disease This Phase 1/2 clinical trial will test the safety and effectiveness of the experimental drug MIB-626 to improve cognitive and daily functioning in people with ...

3. alzdiscovery.org alzdiscovery.org/uploads/cognitive_vitality_media/Nicotinamide_Mononucleotide_(drug_in_development).pdf

Nicotinamide Mononucleotide Secondary outcomes include changes in CSF levels of MIB-626 metabolites, change in NAD+ levels in the brain (MRS), change in NAD+ levels in peripheral blood.

4. sciencedirect.com sciencedirect.com/science/article/pii/S2161831323013595

The Safety and Antiaging Effects of Nicotinamide ... NMN supplementation increases NAD + concentration and could mitigate aging-related disorders such as oxidative stress, DNA damage, neurodegeneration, and ...

5. probiologists.com probiologists.com/article/insight-into-the-application-of-nicotinamide-mononucleotide-nmn-to-age-related-disorders

Insight into the application of nicotinamide mononucleotide ... Oral intake of NMN effectively increased blood levels of NAD+ and NAD+ precursors, such as NMN and NR, compared to the placebo group.

6. rally.massgeneralbrigham.org rally.massgeneralbrigham.org/study/nmn_ad_study

Have you or a loved one been diagnosed with Alzheimer's ... We are conducting this study to determine how MIB-626 affects individuals with Alzheimer's disease. ... and our data indicates that this dose is safe. Study ...