What side effects are associated with this type of intervention?

Common treatments for Alzheimer's Disease include cholinesterase inhibitors (e.g., donepezil, rivastigmine, galantamine) and NMDA receptor antagonists (e.g., memantine). Known side effects of cholinesterase inhibitors can include nausea, vomiting, diarrhea, muscle cramps, and fatigue. Memantine may cause dizziness, headache, confusion, and constipation. For NAD+ precursors/enhancers like MIB-626, specific side effects are not well-documented, but potential side effects could include gastrointestinal issues and changes in metabolic markers, as these are common with similar metabolic treatments.

What prior FDA approvals exist?

The FDA has approved several treatments for Alzheimer's Disease, focusing primarily on symptomatic relief and slowing disease progression. Cholinesterase inhibitors such as donepezil, rivastigmine, and galantamine are commonly used to improve cognitive function by increasing acetylcholine levels in the brain. Memantine, an NMDA receptor antagonist, is another approved drug that helps manage symptoms by regulating glutamate activity. While these treatments do not directly relate to NAD+ precursors or enhancers like MIB-626, they represent the current standard of care. Research into NAD+ precursors, such as MIB-626, aims to explore new therapeutic pathways by potentially enhancing cellular energy metabolism and neuroprotection.

What other types of research exist?

A promising novel alternative to MIB-626 for Alzheimer's Disease patients is RS-0406, which has shown potential in inhibiting amyloid beta fibrillogenesis and protecting neurons against amyloid beta-induced toxicity. This agent could become a therapeutic option for AD patients.

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Sirtuin-NAD Activator

Sirtuin-NAD Activator for Alzheimer's Disease

Phase 1 & 2

Recruiting

Led By Shalender Bhasin, MD

Research Sponsored by Brigham and Women's Hospital

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

A man or a woman between the ages of 55 and 85 years (inclusive)

Meets National Institute on Aging-Alzheimer's Association (NIA-AA) clinical diagnostic criteria for AD dementia

Must not have

Current use of anticoagulants; significant back or spine disease that would make a lumbar puncture difficult or unsafe as determined by a clinician

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

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 90

Summary

This trial tests if MIB-626, a pill that boosts NAD levels, can cross into the brain and help people with mild Alzheimer's disease. The goal is to see if it improves brain health and reduces aging markers. NADH has been previously tested in Alzheimer's disease with mixed results, showing some cognitive improvements in some studies but not in others.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects aren't specified here but may include typical drug reactions such as gastrointestinal issues, headaches, dizziness, or allergic reactions based on its impact on brain chemistry.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am between 55 and 85 years old.

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

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My memory test score is lower than expected for my education level.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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I do not have major neurological conditions other than Alzheimer's that could affect my thinking.

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I have not had major depression, bipolar, schizophrenia, or severe mental health issues in the last year that could affect study participation.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 90

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~90

This trial's timeline: 3 weeks for screening, Varies for treatment, and 90 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

change in CSF concentrations of MIB-626

Secondary study objectives

change in CSF concentrations of MIB-626 metabolites, nicotinamide (NAM), NR, 2-PY, and MeNAM

change in NAD concentrations in peripheral blood mononuclear cells

Brain

+1 more

Other study objectives

Change in circulating biomarkers of amyloid deposition (Aβ-42, Aβ-40), neuronal/axonal degeneration (t-tau, p-tau, NFL), synaptic function (neurogranin), and neuroinflammation (YKL40, GFAP)

Change in cognition

Change in instrumental activities of daily living (IADL)

+2 more

Side effects data

From 2022 Phase 2 trial • 7 Patients • NCT04817111

14%

Constipation

14%

Belching

14%

Back pain

14%

Neck pain

14%

Insomnia

100%

80%

60%

40%

20%

Study treatment Arm

Open Label - MIB-626

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: MIB-626Experimental Treatment1 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 TabletPlacebo Group1 Intervention

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

MIB-626

2021

Completed Phase 2

~50

0 / 6Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Alzheimer's Disease (AD) include cholinesterase inhibitors (e.g., donepezil, rivastigmine) and NMDA receptor antagonists (e.g., memantine). Cholinesterase inhibitors work by preventing the breakdown of acetylcholine, a neurotransmitter important for learning and memory, thereby enhancing cholinergic function. Memantine regulates glutamate activity to prevent excitotoxicity, which can damage neurons. Emerging treatments like MIB-626, a NAD+ precursor/enhancer, aim to boost cellular NAD+ levels, which are crucial for mitochondrial function, DNA repair, and cellular metabolism. Enhancing NAD+ levels may help mitigate neurodegeneration and improve cognitive function in AD patients by supporting neuronal health and reducing oxidative stress.