Cognition Disorders in Old Age, Cognitive Decline, Mild Cognitive Impairment
Conditions
Keywords
Mild Cognitiive Impairment, Subjective Cognitive Decline
Brief summary
In this research study we want to learn more about whether taking Niagen, a daily supplement containing a form of Vitamin B3, will improve cognitive function, mood, and daily activity in people with Subjective Cognitive Decline (SCD) or Mild Cognitive Impairment (MCI).
Detailed description
Over a 6 month period, we will ask study participants to take both Niagen or a placebo for 8 weeks each and complete research visits ever 4 or 8 weeks. Most research visits will involve a blood draw, cognitive testing, and mood questionnaires. We will ask you to come to our center 4-5 times to complete some study activities in-person. There will be an option to participate in a lumbar puncture sub-study, in which participants would have up to 3 lumbar punctures. There will also be an option to participate in an MRI sub-study, in which participants would have up to 3 MRIs over the course of the study. In between research visits, we will also ask the participants to wear a Fitbit activity tracker and play computerized brain games a few times a week. This will enable us to get a snapshot of each subject's functioning levels day to day and better determine whether or not the supplement is having an effect on the participant.
Interventions
DIETARY_SUPPLEMENTNiagen
Nicotinamide Riboside
DIETARY_SUPPLEMENTPlacebo Comparator
Placebo
Sponsors
Steven E Arnold, MD
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Participants were randomized into 2 Treatment sequences, one starting with Placebo followed by Niagen; and the other sequence starting with Active Niagen and followed by Placebo.
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Ages 60 and up; 2. Memory and other cognitive complaints consistent with SCD or MCI as defined by the National Institute on Aging: a. SCD will be defined as: i. any subjective concern of change in cognitive functioning without objective evidence of cognitive impairment, and ii. complete preservation of functional abilities and independence in instrumental activities of daily living. b. MCI will be defined as: i. a preexisting diagnosis of MCI given by a trained physician or behavioral health provider, or ii. evidence of objective impairment in cognitive functioning in one or more domain with preservation of functional abilities and independence in instrumental activities of daily living as defined by the National Institute on Aging; 3. Minimum score of 16 on t-MoCA; 4. Ability to provide direct informed consent as assessed by obtaining a score of 70% on questions 1-10, and answer 'yes' to questions 11-14 of the Informed Consent Worksheet after two attempts; 5. Education level, English language skills and literacy indicates participant able to complete all assessments; 6. Willing and able to complete all assessment and study procedures; 7. Not pregnant, lactating, or of child-bearing potential; 8. If on cholinesterase inhibitor and/or memantine, doses are stable for 3 months prior to baseline.
Exclusion criteria
1. Any specific CNS disease history other than suspected ADRD, such as major clinical stroke, brain tumor, normal pressure hydrocephalus, multiple sclerosis, significant head trauma with persistent neurological of cognitive deficits or complaints; 2. Any impairment in instrumental activities of daily living that would indicate a level of cognitive impairment beyond MCI as assessed by a trained rater; 3. Clinically significant unstable medical condition that could affect safety or compliance with the study and would, in the opinion of the investigator, pose a risk to the participant if they were to participate in the study; 4. History of neuroimaging with evidence of major infarction, injury, infection, or other focal lesions that may be related to cognitive dysfunction; 5. If participating in the optional lumbar puncture sub-study, any contraindication to undergo lumbar punctures, such as: 1. abnormal coagulation PT/INR test result, outside of the normal range of 0.9 to 1.2 platelet counts below 50,000 (determined by a licensed study physician or Nurse Practitioner after reading test results). 2. Platelet counts below 50,000. 3. Use of Coumadin, Warfarin, or other blood thinner medications. 4. Infection near the puncture site, or spinal column deformities (a licensed physician or Nurse Practitioner will examine the site visually for infection or spinal deformities before performing the procedure). 5. Known allergy to Lidocaine. 6. Major active or chronic unstable psychiatric illness (e.g. depression, bipolar disorder, obsessive compulsive disorder, schizophrenia) within the previous year; 7. Current suicidal ideation or history of suicide attempt; 8. History of alcohol or other substance abuse or dependence within the past two years; 9. Any significant systemic illness or medical condition that could affect safety or compliance with study; 10. Laboratory abnormalities in Vitamin B12, Thyroid Stimulating Hormone (TSH), or other common laboratory parameters that might contribute to cognitive dysfunction or other abnormalities in hematological, hepatic or renal function tests; 11. Current use of medications with psychoactive properties that in the opinion of the principal investigator, may be deleteriously affecting cognition (e.g., anticholinergics, antihistamines, antipsychotics, sedative hypnotics, anxiolytics); 12. Any known hypersensitivity to nicotinamide riboside, or its principal metabolite, nicotinamide mononucleotide; 13. No consumption of dietary supplements containing more than 100mg niacin, nicotinamide riboside (NR), or nicotinamide mononucleotide (NMN) as the primary agents 30 days prior to baseline and for the duration of the trial; 14. Use of other investigational agents or interventions one month prior to entry and for the duration of the trial; 15. If participating in the optional MR sub-study: Any contraindication to undergo MRI studies, such as history of cardiac pacemaker or pacemaker wires, metallic particles in the body, vascular clips in the head, prosthetic heart valves, and/or severe claustrophobia impeding ability to participate in an imaging study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Effect of Niagen vs PBO on Cognition as Measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). | From baseline through end of study at 16 weeks | The primary outcome of this study will be objective measures of cognitive performance measured with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) at baseline, crossover, and the end of study. RBANS has a mean score of 100 with a standard deviation of 15. Scores range from 40 to 160. Higher scores indicate normal cognition. |
Countries
United States
Participant flow
Pre-assignment details
61 Participants signed consent and enrolled in the study. Prior to randomization assignment, 15 participants screen failed. 46 proceeded to randomization assignment and study lead-in.
Participants by arm
| Arm | Count |
|---|---|
| Sequence 1: Active Niagen, Placebo Subjects received 1000 mg Niagen and PBO dispensed in randomized blocks. Participants in Sequence 1 took Niagen daily for 8 weeks, followed by Placebo daily for 8 weeks.
Niagen: Nicotinamide Riboside
Placebo Comparator: Placebo | 23 |
| Sequence 2: Placebo, Active Niagen Subjects received 1000 mg Niagen and PBO dispensed in randomized blocks. Participants in Sequence 2 took Placebo daily for 8 weeks, followed by Active Niagen daily for 8 weeks.
Niagen: Nicotinamide Riboside
Placebo Comparator: Placebo | 23 |
| Total | 46 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Baseline/Initial Treatment (8 Weeks) | Early Termination | 1 | 0 |
| Baseline/Initial Treatment (8 Weeks) | Withdrawal by Subject | 1 | 2 |
| Crossover Treatment (8 Weeks) | Early Termination | 0 | 1 |
| Lead-In Period (4-Weeks) | Screen Fail | 1 | 2 |
| Lead-In Period (4-Weeks) | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Sequence 1: Active Niagen, Placebo | Sequence 2: Placebo, Active Niagen | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 16 Participants | 11 Participants | 27 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 12 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants | 23 Participants | 46 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 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 | 3 Participants | 4 Participants | 7 Participants |
| Race (NIH/OMB) White | 20 Participants | 17 Participants | 37 Participants |
| Region of Enrollment United States | 23 participants | 23 participants | 46 participants |
| Sex: Female, Male Female | 13 Participants | 13 Participants | 26 Participants |
| Sex: Female, Male Male | 10 Participants | 10 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 20 | 0 / 20 | 0 / 18 |
| other Total, other adverse events | 3 / 22 | 2 / 20 | 3 / 20 | 1 / 18 |
| serious Total, serious adverse events | 0 / 22 | 0 / 20 | 1 / 20 | 2 / 18 |
Outcome results
Primary
The Effect of Niagen vs PBO on Cognition as Measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
The primary outcome of this study will be objective measures of cognitive performance measured with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) at baseline, crossover, and the end of study. RBANS has a mean score of 100 with a standard deviation of 15. Scores range from 40 to 160. Higher scores indicate normal cognition.
Time frame: From baseline through end of study at 16 weeks
Population: Participants that completed the trial were analyzed (20 in sequence 1; 17 in sequence 2)
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Sequence 1: Active Niagen, Placebo | The Effect of Niagen vs PBO on Cognition as Measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). | 1st intervention/crossover 8 weeks | 94.87 units on a scale | Standard Error 2.68 |
| Sequence 1: Active Niagen, Placebo | The Effect of Niagen vs PBO on Cognition as Measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). | Baseline | 92.15 units on a scale | Standard Error 2.68 |
| Sequence 1: Active Niagen, Placebo | The Effect of Niagen vs PBO on Cognition as Measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). | 16 weeks/end of study | 93 units on a scale | Standard Error 3.1 |
| Sequence 2: Placebo, Active Niagen | The Effect of Niagen vs PBO on Cognition as Measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). | Baseline | 91.04 units on a scale | Standard Error 3.15 |
| Sequence 2: Placebo, Active Niagen | The Effect of Niagen vs PBO on Cognition as Measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). | 1st intervention/crossover 8 weeks | 95.17 units on a scale | Standard Error 3.16 |
| Sequence 2: Placebo, Active Niagen | The Effect of Niagen vs PBO on Cognition as Measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). | 16 weeks/end of study | 95.64 units on a scale | Standard Error 3.58 |