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NCT Number: NCT05483465

The Effect of NAD Supplementation on Brain Vascular Health in Aging

Daily consumption of one of the forms of Vitamin B3, the Nicotinamide Riboside (NR), energizes the body and combats cellular aging. This study is designed to test whether NR can also improve brain health and memory.

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Key information

Conditions

Age range

60 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

About this study

This study is designed to test the hypothesis that restoration of Nicotinamide Adenine Dinucleotide (NAD) levels with Nicotinamide Riboside (NR) in older adults will improve neurovascular coupling (NVC) responses and micro- and macrovascular endothelial function. This hypothesis will be tested by assessing the effects of treatment with oral NR (1g/day per os for 8 weeks) or placebo (8 weeks) in community dwelling older adults (60-85 years of age).

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age ≥60 and ≤85 years of age
  • Adequate hearing and visual acuity to participate in the examinations
  • Ability to read and write in English
  • Competence to provide informed consent.
  • Mini-Mental State Exam score ≥24

Exclusion criteria

  • Vision or hearing impairment that would impair the ability to complete study assessments
  • Active CNS disease including multiple sclerosis, uncontrolled seizures, active brain cancer
  • Cerebrovascular accident other than TIA within 60 days prior to Visit 0
  • Major psychiatric disease, including major depression not currently controlled on medications, alcohol or drug abuse
  • Abnormal kidney function (creatinine >2mg/dL or EGFR <30mL/min) by most recent labs within 6 months prior to Visit 0
  • Elevated liver enzymes (AST and/or ALT above x2 upper limit of normal) by most recent labs within 6 months prior to Visit 0
  • Treatment with other NAD enhancers (Nicotinamide riboside or nicotinamide mononucleotide) within 4 weeks prior to randomization.
  • Any other medical condition which, in the opinion of investigator, would render the patient inappropriate or too unstable to complete the study protocol

Treatment and study plan

Nicotinamide riboside

Drug

Oral NR, 1g/day per os for 8 weeks

Other names: NR

Placebo

Drug

Visually identical pill to NR, daily per os for 8 weeks

Other names: Sugar pill

Primary outcomes

  1. Change in neurovascular coupling using functional near infrared spectroscopy (fNIRS)

    Time frame: 8 weeks

    Functional near infrared spectroscopy (fNIRS) will be performed during the cognitive n-back task. fNIRS approach generates data that represent a relative change in oxygenated and deoxygenated hemoglobin measured over the cortical brain tissues. Neurovascular coupling will be evaluated as a change in oxy- and deoxy-hemoglobin between before and after treatment. Units of measure - beta. Reported as a %change from baseline, before and after treatment.

  2. Change in neurovascular coupling using transcranial Doppler

    Time frame: 8 weeks

    Transcranial Doppler sonography will be used to measure the change in the blood flow velocities during the cognitive n-back task between before and after treatment. Units of measure - % change between the n-back tasks. Reported as a %change from baseline, before and after treatment.

  3. Change in neurovascular coupling using the dynamic retinal vessel analysis

    Time frame: 8 weeks

    Flicker light-induced dilation of the retinal vessels (percentage increase over baseline diameter) will be measured in the right or left eye of each study participant using the Dynamic Vessel Analyzer (DVA, IMEDOS Systems, Jena, Germany). Units of measure mm, reported as a %change from baseline, before and after treatment.

  4. Change in neuronal activity

    Time frame: 8 weeks

    EEG signal will be collected to generate spectral data. These data will be used for comparison of EEG activity between before and after treatment. Units of measure - power spectral density. Reported as a %change from baseline, before and after treatment.

Secondary outcomes

  1. Change in microvascular endothelial function

    Time frame: 8 weeks

    Changes in microvascular endothelial function will be assessed using laser speckle contrast imaging (LSCI) in the hand using the flow mediated dilation approach. The change in skin perfusion is calculated and reported as a %change from baseline, between before and after treatment. Units of measure - perfusion index (arbitrary units). Reported as a %change from baseline, before and after treatment.

  2. Change in macrovascular endothelial function

    Time frame: 8 weeks

    Changes in macrovascular endothelial function will be assessed using sonography during flow mediated dilation approach. The change in brachial artery diameter (mm) is calculated and reported as a %change from baseline, between before and after treatment.

  3. Change in deep tissue oxygen saturation

    Time frame: 8 weeks

    Transcutaneous deep tissue oxygen saturation will be measured using the inSpectra near infrared device. The data are calculated and reported as a %change from baseline, between before and after treatment.

  4. Change in arterial stiffness

    Time frame: 8 weeks

    The arterial stiffness will be measured using the pulse wave analysis approach (SphygmoCor, Atcor medical, Itasca IL, or similar). Analysis generates the augmentation index which will be used for comparison before and after treatment.

  5. Change in ECG

    Time frame: 8 weeks

    ECG will be recorded for heart rate variability analysis. The values of high frequency domain, low frequency domain, their ratio, as well as total power will be calculated and used for comparison before and after treatment.

  6. Change in Glycocalyx - perfused boundary region

    Time frame: 8 weeks

    Video recordings of the sublingual vasculature will be performed using the high definition video camera GlycoCheck (Microvascular health solutions). Data collected will include perfused boundary region (um), and will be used for comparison before and after treatment.

  7. Change in capillary density

    Time frame: 8 weeks

    Video recordings of the sublingual vasculature will be performed using the high definition video camera GlycoCheck (Microvascular health solutions). Data collected will include capillary density (mm/mm^2), and will be used for comparison before and after treatment.

  8. Change in red blood cell velocity

    Time frame: 8 weeks

    Video recordings of the sublingual vasculature will be performed using the high definition video camera GlycoCheck (Microvascular health solutions). Data collected will include red blood cell velocity (um/sec), and will be used for comparison before and after treatment.

  9. Change in Attention

    Time frame: 8 weeks

    The allocation of one's limited capacities to deal with an abundance of environmental stimulation will be measured in a combined "Flanker Inhibitory Control and Attention Test".Units of measure - score (from 0 to 10, bigger number is better). Reported as a %change from baseline, before and after treatment.

  10. Change in Episodic Memory

    Time frame: 8 weeks

    Cognitive processes involved in the acquisition, storage and retrieval of new information, will be measured using the "Picture Sequence Memory Test". Unit of measure - overall score (bigger number is better). Reported as a %change from baseline, before and after treatment.

  11. Change in Working Memory

    Time frame: 8 weeks

    The ability to store information until the amount of information to be stored exceeds one's capacity to hold that information will be measured using the "List Sorting Working Memory Test". Unit of measure - overall score (bigger number is better). Reported as a %change from baseline, before and after treatment.

  12. Change in Language

    Time frame: 8 weeks

    Picture Vocabulary Test measures receptive vocabulary administered in a computer-adaptive test (CAT) format. Respondents select the picture that most closely matches the meaning of the word, before and after treatment. Unit of measure - overall score (bigger number is better). Reported as a %change from baseline, before and after treatment.

  13. Change in Executive Function

    Time frame: 8 weeks

    The capacity to plan, organize and monitor the executive of behaviors that are strategically directed in a goal-oriented manner will be measured using the "Dimensional Change Card Sort Test". Units of measure - score (from 0 to 10, bigger number is better). Reported as a %change from baseline, before and after treatment.

  14. Change in Processing Speed

    Time frame: 8 weeks

    Pattern Comparison Processing Speed Test assesses the amount of information that can be processed within a certain unit of time. Items are simple so as to purely measure processing speed. Units of measure - score (from 0 to 130, bigger number is better). Reported as a %change from baseline, before and after treatment.

  15. Blood collection

    Time frame: 8 weeks

    Blood samples will be collected to measure concentration of NAD metabolites for comparison before and after treatment. Blood samples will also be used in in vitro assays to measure the effect of treatment on endothelial function.

Study contacts

Contact information is provided by the study sponsor or research team.

Andriy Yabluchanskiy, MD, PhD

CONTACT

[email protected]

405-271-7622

Sponsors and collaborators

Lead sponsor

University of Oklahoma

Other

Collaborators

  • Elysium Health
  • Oklahoma Medical Research Foundation
  • University of Pennsylvania

Registry information

Official study title

Effects of NAD Restoration on Neurovascular Coupling in Community Dwelling Older Adults

Important dates

Study start
2023
Primary completion
2027
Study completion
2027
First posted
Aug 2, 2022
Registry last updated
Apr 1, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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