The Effect of NAD Supplementation on Brain Vascular Health in Aging

Aging Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05483465
• Other study ID #: 14782
• Status: Recruiting
• Phase: Phase 4
• Start date: May 3, 2023
• Est. completion date: December 2027

Study information

• Verified date: May 2023
• Source: University of Oklahoma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 214
• Est. completion date: December 2027
• Est. primary completion date: June 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 60 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Aging

Intervention

Drug:
• Nicotinamide riboside
Oral NR, 1g/day per os for 8 weeks
• Placebo
Visually identical pill to NR, daily per os for 8 weeks

Locations

Country	Name	City	State
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma

Sponsors (4)

Lead Sponsor	Collaborator
University of Oklahoma	Elysium Health, Oklahoma Medical Research Foundation, University of Pennsylvania

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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