RECRUITING

Sirtuin-NAD Activator in Alzheimer's Disease

Conditions

Alzheimer's Disease (Incl Subtypes)Dementia NAD MIB-626

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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).

Official Title

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

Quick Facts

Study Start:2021-12-01

Study Completion:2024-12-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05040321

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:55 Years to 85 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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	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.

Inclusion Criteria

Exclusion 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

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.

Contacts and Locations

Study Contact

Shalender Bhasin, MD

CONTACT

6175259150

sbhasin@bwh.harvard.edu

Gad Marshall, MD

CONTACT

617-732-8060

GAMARSHALL@PARTNERS.ORG

Principal Investigator

Shalender Bhasin, MD

PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Neha K Rupeja, MS

STUDY_DIRECTOR

Brigham and Women's Hospital

Study Locations (Sites)

Brigham and Women's Hospital

Boston, Massachusetts, 02115-0000

United States

Collaborators and Investigators

Sponsor: Brigham and Women's Hospital

Shalender Bhasin, MD, PRINCIPAL_INVESTIGATOR, Brigham and Women's Hospital
Neha K Rupeja, MS, STUDY_DIRECTOR, Brigham and Women's Hospital

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-12-01

Study Completion Date2024-12-01

Study Record Updates

Study Start Date2021-12-01

Study Completion Date2024-12-01

Terms related to this study

Keywords Provided by Researchers

Dementia
NAD
MIB-626

Additional Relevant MeSH Terms

Alzheimer's Disease (Incl Subtypes)
Dementia