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

NCT03482167 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 1079271K01AG054731
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

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.

Conditions

Mild Cognitive Impairment

Keywords

blood pressure; arterial stiffness; cerebrovascular function; cognitive function

Outcome Measures

Primary Outcomes (1)

• 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).

  baseline and 12 weeks

Secondary Outcomes (4)

• Cerebrovascular Reactivity at Baseline and 12 Weeks

  baseline and 12 weeks

• Total Brain Blood Flow at Baseline and 12 Weeks

  baseline and 12 weeks

• Aortic Stiffness at Baseline and 12 Weeks

  baseline and 12 weeks

• Blood Pressure at Baseline and 12 Weeks

  baseline and 12 weeks

Other Outcomes (4)

• Neurovascular Coupling at Baseline and 12 Weeks

  baseline and 12 weeks

• Functional Brain Connectivity at Baseline and 12 Weeks

  baseline and 12 weeks

• Neuronal Activation at Baseline and 12 Weeks

  baseline and 12 weeks

Study Arms (2)

Placebo

PLACEBO COMPARATOR

placebo

Other: Placebo

Nicotinamide Riboside

EXPERIMENTAL

Niagen® (ChromaDex, Inc.) 500 mg, twice daily

Drug: Niagen®

Interventions

Niagen® DRUG

250 mg capsules (4 capsules daily)

Also known as: nicotinamide riboside chloride

Nicotinamide Riboside

Placebo OTHER

placebo

Placebo

Eligibility Criteria

• Age: 60 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Delaware: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

Neurovascular Aging Laboratory

Newark, Delaware, 19713, United States

Location

MeSH Terms

Conditions

Cognitive Dysfunction

Interventions

nicotinamide-beta-riboside

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Limitations and Caveats

Technical problems with ultrasound measures leading to unreliable or uninterpretable data in some participants. Total brain blood flow was therefore assessed in all participants by MRI using pseudo-continuous arterial spin labeling (pCASL).

Results Point of Contact

• Title: Christopher R. Martens, Ph.D.
• Organization: University of Delaware

cmartens@udel.edu

302-831-7270

Study Officials

• Christopher R Martens, Ph.D.

  University of Delaware

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double-blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: February 14, 2018
• First Posted: March 29, 2018
• Study Start: March 20, 2019
• Primary Completion: January 8, 2024
• Study Completion: January 22, 2024
• Last Updated: April 4, 2025
• Results First Posted: April 4, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)