The Effect of NAD Supplementation on Brain Vascular Health in Aging

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

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.

Study Overview

• Status: Recruiting
• Conditions: Aging
• Intervention / Treatment: Drug: Nicotinamide riboside; Drug: Placebo

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Anticipated): 214
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73117
      • Recruiting
      • University of Oklahoma Health Sciences Center
      • Contact: Andriy Yabluchanskiy, MD, PhD; Phone Number: 405-271-8130; Email: andriy-yabluchanskiy@ouhsc.edu
      • Contact: Peter Mukli, MD, PhD; Phone Number: 47097 405-271-8000; Email: peter-mukli@ouhsc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NR; Treatment with oral NR (1g/day per os for 8 weeks)	Drug: Nicotinamide riboside; Oral NR, 1g/day per os for 8 weeks; Other Names: NR
Placebo Comparator: Control; Visually identical placebo (daily, per os, for 8 weeks)	Drug: Placebo; Visually identical pill to NR, daily per os for 8 weeks; Other Names: Sugar pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in neurovascular coupling using functional near infrared spectroscopy (fNIRS)	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.	8 weeks
Change in neurovascular coupling using transcranial Doppler	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.	8 weeks
Change in neurovascular coupling using the dynamic retinal vessel analysis	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.	8 weeks
Change in neuronal activity	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.	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in microvascular endothelial function	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.	8 weeks
Change in macrovascular endothelial function	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.	8 weeks
Change in deep tissue oxygen saturation	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.	8 weeks
Change in arterial stiffness	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.	8 weeks
Change in ECG	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.	8 weeks
Change in Glycocalyx - perfused boundary region	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.	8 weeks
Change in capillary density	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 weeks
Change in red blood cell velocity	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.	8 weeks
Change in Attention	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.	8 weeks
Change in Episodic Memory	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.	8 weeks
Change in Working Memory	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.	8 weeks
Change in Language	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.	8 weeks
Change in Executive Function	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.	8 weeks
Change in Processing Speed	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.	8 weeks
Blood collection	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.	8 weeks

Collaborators and Investigators

• Sponsor: University of Oklahoma
• Collaborators: University of Pennsylvania; Elysium Health; Oklahoma Medical Research Foundation

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2023
• Primary Completion (Anticipated): June 1, 2027
• Study Completion (Anticipated): December 1, 2027

Study Registration Dates

• First Submitted: July 29, 2022
• First Submitted That Met QC Criteria: July 29, 2022
• First Posted (Actual): August 2, 2022

Study Record Updates

• Last Update Posted (Actual): May 10, 2023
• Last Update Submitted That Met QC Criteria: May 8, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: cognitive function; endothelial function; NAD; neurovascular coupling; nicotinamide riboside; NR
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Antimetabolites; Micronutrients; Hypolipidemic Agents; Lipid Regulating Agents; Vitamins; Vitamin B Complex; Nicotinic Acids; Niacinamide; Niacin
• Other Study ID Numbers: 14782

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The results may be uploaded to scientific online repositories such as PhysioNet (or other) as requested by the journal when data is submitted for publication. In that case, all data will be de-identified and labeled by group+number (for example Placebo1, Placebo2, NR1, NR2, these IDs will be different from study IDs stored on the servers at the OUHSC) and supported by subjects' age, sex, comorbidities and treatments data.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No