NAD Therapy for Improving Memory and Brain Blood Flow in Older Adults With Mild Cognitive Impairment

Status

Completed

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03482167

Enrollment

Registered

2018-03-29

Start date

2019-03-20

Completion date

2024-01-22

Last updated

2025-04-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Mild Cognitive Impairment

Keywords

blood pressure, arterial stiffness, cerebrovascular function, cognitive function

Brief summary

This study will provide insight into whether a nutritional supplement, nicotinamide riboside (NR), improves memory and brain blood flow in older adults with low memory abilities. Overall, this project has the potential to identify a novel, safe and cost-effective strategy for decreasing age-related memory loss.

Interventions

DRUGNiagen®

250 mg capsules (4 capsules daily)

OTHERPlacebo

placebo

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Masking description

Double-blind

Eligibility

Sex/Gender

ALL

Age

60 Years to 90 Years

Healthy volunteers

Inclusion criteria

* Cognitive function scores consistent with amnestic mild cognitive impairment based on pre-screening evaluation; * age 60-90 years; * MMSE score \>24 at time of initial consent;

Exclusion criteria

* blood chemistries indicative of abnormal renal, liver, thyroid and adrenal function; estimated glomerular filtration rate using the MDRD prediction equation must be \>30 ml/min/1.73 m2; * any clinically significant abnormal blood chemistry values as determined by the research nurse or NMPCC nurse practitioner; * major psychiatric disorder (e.g. schizophrenia, bipolar disorder, major depression within past two years); * neurological or autoimmune conditions affecting cognition (e.g. Parkinson's disease, epilepsy, multiple sclerosis, mild or severe traumatic brain injury, large vessel infarct); * concussion within last 2 years and ≥ 3 lifetime concussions; * current systemic medical illnesses (e.g. cardiovascular disease, cancer, renal failure); * prior history of any type of cancer; * substance abuse or dependence (DSM-V criteria); * current use of medications used to treat dementia (e.g., anticholinesterase drugs) or other drugs likely to affect cognition (e.g., anticholinergic drugs, long-acting benzodiazepines); * claustrophobia, metal implants, pacemaker or other factors affecting feasibility and/or safety of MRI scanning\*; * current smoking (including marijuana) within the past 3 months; * hospitalization as a result of COVID-19

Design outcomes

Primary

Measure	Time frame	Description
Cognitive Scores at Baseline and Week 12	baseline and 12 weeks	Primary outcome was a change from baseline in any domain of cognitive function. For all outcomes, a higher score indicates better cognitive function: 1. California Verbal Learning Test III (CVLT-III) Index Scores. Ability learn and recall a list of words over 5 trials and again after a 20 minute delay. Each Index Score has a mean of 100 and a standard deviation of 15 based on normative dataset (Range = 55 - 145). 2. Wechsler Memory Scale IV (WMS-IV) Raw Scores. * Logical Memory I & II: Range = 0-50 * Logical Memory II Recognition: Range = 0-30 * Visual Reproduction I & II: Range = 0-43 * Visual Reproduction II Recognition Score: Range = 0-7 3. NIH Toolbox Fluid Composite Score. Composite Score has a mean of 100 and a standard deviation of 15 based on normative dataset (Range = 55 - 145) - based on several tests of fluid and crystallized cognition (episodic memory, attention, working memory, processing speed, executive function and language abilities).

Secondary

Measure	Time frame	Description
Total Brain Blood Flow at Baseline and 12 Weeks	baseline and 12 weeks	Total brain blood flow assessed by pseudo-continuous arterial spin labeling (pcASL). Total brain blood flow is measured in milliliters of blood per minute per 100 grams of brain tissue.
Aortic Stiffness at Baseline and 12 Weeks	baseline and 12 weeks	Carotid-femoral pulse wave velocity (CFPWV)
Blood Pressure at Baseline and 12 Weeks	baseline and 12 weeks	Seated systolic and diastolic blood pressure assessed using automated oscillometric sphygmomanometer.
Cerebrovascular Reactivity at Baseline and 12 Weeks	baseline and 12 weeks	Relative (percent) change in blood velocity of the middle cerebral artery (MCA) per mmHg change in end-tidal carbon dioxide (ETCO2) during a brief period of hypercapnia. Hypercapnia was induced by prospective end-tidal targeting (RespirAct, Thornhill Medical) in which a target change in end-tidal CO2 of +9mmHg was set. Data were only analyzed if ETCO2 changed by at least 6mmHg. All data were then normalized to the absolute change in ETCO2.

Other

Measure	Time frame	Description
Neurovascular Coupling at Baseline and 12 Weeks	baseline and 12 weeks	Cerebrovascular reactivity to cognitive tasks
Functional Brain Connectivity at Baseline and 12 Weeks	baseline and 12 weeks	functional brain connectivity assessed by MRI
Neuronal Activation at Baseline and 12 Weeks	baseline and 12 weeks	Functional MRI (fMRI) to cognitive task
Brain Volume at Baseline and 12 Weeks	baseline and 12 weeks	White and grey matter volume assessed by structural MRI

Countries

United States

Participant flow

Recruitment details

Participants were screened for inclusion in this study at the University of Delaware between March 20, 2019 - August 21, 2023.

Pre-assignment details

A total of 64 participants were consented into this study. Of these, 13 participants were withdrawn prior to randomization. Reasons for withdrawal inlcluded not meeting eligibility criteria (N = 7), failure to comply with study requirements (N = 1), voluntarily withdrawal by the participant (N = 2), or if a participant was lost to followup (N = 2).

Participants by arm

Arm	Count
Placebo Placebo Placebo: Placebo	25
Nicotinamide Riboside Niagen® (ChromaDex, Inc.) 500 mg, twice daily Niagen®: 250 mg capsules (4 capsules daily)	24
Total	49

Withdrawals & dropouts

Period	Reason	FG000	FG001
Allocated to Intervention	Physician Decision	1	2
Received Intervention	Adverse Event	3	1
Received Intervention	Physician Decision	1	1
Received Intervention	Withdrawal by Subject	1	0

Baseline characteristics

Characteristic	Nicotinamide Riboside	Placebo	Total
Age, Continuous	72 years STANDARD_DEVIATION 8	71 years STANDARD_DEVIATION 7	72 years STANDARD_DEVIATION 8
APOE Genotype ε2/ε2	0 Participants	0 Participants	0 Participants
APOE Genotype ε2/ε3	4 Participants	6 Participants	10 Participants
APOE Genotype ε2/ε4	0 Participants	2 Participants	2 Participants
APOE Genotype ε3/ε3	10 Participants	9 Participants	19 Participants
APOE Genotype ε3/ε4	9 Participants	8 Participants	17 Participants
APOE Genotype ε4/ε4	1 Participants	0 Participants	1 Participants
APOE ε4 Carrier	10 Participants	10 Participants	20 Participants
Clinical Dementia Rating - Global Score	0.4 units on a scale STANDARD_DEVIATION 0.2	0.4 units on a scale STANDARD_DEVIATION 0.2	0.4 units on a scale STANDARD_DEVIATION 0.2
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants	1 Participants	2 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	23 Participants	24 Participants	47 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Mini Mental State Exam (MMSE)	26 Units on a scale STANDARD_DEVIATION 2	27 Units on a scale STANDARD_DEVIATION 2	27 Units on a scale STANDARD_DEVIATION 2
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	2 Participants	2 Participants
Race (NIH/OMB) Black or African American	1 Participants	7 Participants	8 Participants
Race (NIH/OMB) More than one race	1 Participants	0 Participants	1 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	22 Participants	16 Participants	38 Participants
Revised Brief Visuospatial Memory Test (BVMT-R) Total Recall Score	33 T-Score STANDARD_DEVIATION 8	35 T-Score STANDARD_DEVIATION 13	35 T-Score STANDARD_DEVIATION 8
Revised Hopkins Verbal Learning Test (HVLT-R) Total Recall Memory	38 T-Score STANDARD_DEVIATION 8	39 T-Score STANDARD_DEVIATION 8	39 T-Score STANDARD_DEVIATION 8
Revised Wechsler Memory Scale (WMS-R) - Logical Memory I	8 units on a scale STANDARD_DEVIATION 3	8 units on a scale STANDARD_DEVIATION 3	8 units on a scale STANDARD_DEVIATION 3
Sex: Female, Male Female	13 Participants	18 Participants	31 Participants
Sex: Female, Male Male	11 Participants	7 Participants	18 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 25	0 / 24
other Total, other adverse events	12 / 25	8 / 24
serious Total, serious adverse events	0 / 25	0 / 24

Outcome results

Primary

Cognitive Scores at Baseline and Week 12

Primary outcome was a change from baseline in any domain of cognitive function. For all outcomes, a higher score indicates better cognitive function: 1. California Verbal Learning Test III (CVLT-III) Index Scores. Ability learn and recall a list of words over 5 trials and again after a 20 minute delay. Each Index Score has a mean of 100 and a standard deviation of 15 based on normative dataset (Range = 55 - 145). 2. Wechsler Memory Scale IV (WMS-IV) Raw Scores. * Logical Memory I & II: Range = 0-50 * Logical Memory II Recognition: Range = 0-30 * Visual Reproduction I & II: Range = 0-43 * Visual Reproduction II Recognition Score: Range = 0-7 3. NIH Toolbox Fluid Composite Score. Composite Score has a mean of 100 and a standard deviation of 15 based on normative dataset (Range = 55 - 145) - based on several tests of fluid and crystallized cognition (episodic memory, attention, working memory, processing speed, executive function and language abilities).