Trial Outcomes & Findings for Clinical Trial of Niagen to Examine Recovery in People With Persistent Cognitive and Physical Symptoms After COVID-19 (NCT NCT04809974)
NCT ID: NCT04809974
Last Updated: 2025-08-05
Results Overview
Cognitive outcomes were assessed using the Everyday Cognition (ECog) scale, Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and the Trail Making Test B (TMT-B). The ECog total score ranges from 39 to 156, and individual domain scores range from 1 to 4. Higher scores indicate greater subjective cognitive decline since COVID-19 infection. Individual RBANS index scores range from 40 to 160, and the Sum of Index Scores (sum of five index scores) ranges from 200 to 800. Higher index scores reflect better cognitive performance. The TMT-B score is the completion time in seconds, with a maximum time of 5 minutes. A lower time is indicative of a better performance. Change scores reflect the difference from Baseline to Week 10, and from Week 10 to Week 20. Positive change scores on the ECog indicate worsening subjective cognitive decline. Positive change scores on the RBANS indicate improvement. Positive change scores in the TMT-B represent worsening performance.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
72 participants
Primary outcome timeframe
Baseline, Week 10 and Week 20
Results posted on
2025-08-05
Participant Flow
Participants were enrolled between August 2021 and September 2023. They were recruited using flyers posted at Massachusetts General Hospital (main and Charlestown campuses), Partners Rally for Research, community events, physician referrals, and outreach to local institutions. Eligibility was assessed via telephone interview and an in-person screening visit.
72 participants provided informed consent and completed an in-person screening visit. Eleven participants were deemed ineligible based on screening assessments and did not proceed. The remaining 61 participants entered a two-week placebo lead-in phase, during which 3 participants withdrew from the study. A total of 58 participants completed the lead-in phase, attended the baseline visit, and were randomized to study intervention.
Participant milestones
| Measure |
Lead-in Phase
Participants assigned to the Lead-in Phase received placebo capsules at the screening visit and were instructed to take four capsules in the morning and four capsules in the evening (8 capsules daily) for two weeks. All capsules were visually identical to the active study drug and administered using the same dosing instructions as the randomized phase.
|
Placebo
Participants randomized to the placebo group received placebo capsules twice daily for 10 weeks following a two-week placebo lead-in period. After the initial 10 weeks, participants crossed over to receive NR (TruNiagen, Chromadex) 1000 mg twice daily for an additional 10 weeks. Dosing was double-blinded. Participants completed assessments of cognitive, neuropsychiatric, physical, functional, and biomarker outcomes, along with actigraphy monitoring.
|
Niagen
Participants randomized to the Niagen group received NR (TruNiagen, Chromadex) 1000 mg twice daily for 20 weeks following a two-week placebo lead-in period. Dosing was double-blinded. Participants completed assessments of cognitive, neuropsychiatric, physical, functional, and biomarker outcomes, along with actigraphy monitoring.
|
|---|---|---|---|
|
Lead-in Phase
STARTED
|
72
|
0
|
0
|
|
Lead-in Phase
Screening
|
72
|
0
|
0
|
|
Lead-in Phase
COMPLETED
|
58
|
0
|
0
|
|
Lead-in Phase
NOT COMPLETED
|
14
|
0
|
0
|
|
Randomized Phase
STARTED
|
0
|
21
|
37
|
|
Randomized Phase
Baseline
|
0
|
21
|
37
|
|
Randomized Phase
Visit 1
|
0
|
21
|
29
|
|
Randomized Phase
Visit 2
|
0
|
18
|
25
|
|
Randomized Phase
Visit 3
|
0
|
18
|
20
|
|
Randomized Phase
Visit 4
|
0
|
18
|
18
|
|
Randomized Phase
Follow-up
|
0
|
17
|
15
|
|
Randomized Phase
COMPLETED
|
0
|
17
|
15
|
|
Randomized Phase
NOT COMPLETED
|
0
|
4
|
22
|
Reasons for withdrawal
| Measure |
Lead-in Phase
Participants assigned to the Lead-in Phase received placebo capsules at the screening visit and were instructed to take four capsules in the morning and four capsules in the evening (8 capsules daily) for two weeks. All capsules were visually identical to the active study drug and administered using the same dosing instructions as the randomized phase.
|
Placebo
Participants randomized to the placebo group received placebo capsules twice daily for 10 weeks following a two-week placebo lead-in period. After the initial 10 weeks, participants crossed over to receive NR (TruNiagen, Chromadex) 1000 mg twice daily for an additional 10 weeks. Dosing was double-blinded. Participants completed assessments of cognitive, neuropsychiatric, physical, functional, and biomarker outcomes, along with actigraphy monitoring.
|
Niagen
Participants randomized to the Niagen group received NR (TruNiagen, Chromadex) 1000 mg twice daily for 20 weeks following a two-week placebo lead-in period. Dosing was double-blinded. Participants completed assessments of cognitive, neuropsychiatric, physical, functional, and biomarker outcomes, along with actigraphy monitoring.
|
|---|---|---|---|
|
Lead-in Phase
Withdrawal by Subject
|
3
|
0
|
0
|
|
Lead-in Phase
No longer eligible
|
11
|
0
|
0
|
|
Randomized Phase
Lost to Follow-up
|
0
|
1
|
5
|
|
Randomized Phase
Met an exclusion criteria during the study (e.g., re-infected with COVID-19, started new medication)
|
0
|
2
|
8
|
|
Randomized Phase
Adverse Event
|
0
|
1
|
4
|
|
Randomized Phase
Withdrawal by Subject
|
0
|
0
|
5
|
Baseline Characteristics
Clinical Trial of Niagen to Examine Recovery in People With Persistent Cognitive and Physical Symptoms After COVID-19
Baseline characteristics by cohort
| Measure |
Placebo
n=21 Participants
Participants randomized to the placebo group received placebo capsules twice daily for 10 weeks following a two-week placebo lead-in period. After the initial 10 weeks, participants crossed over to receive NR (TruNiagen, Chromadex) 1000 mg twice daily for an additional 10 weeks. Dosing was double-blinded. Participants completed assessments of cognitive, neuropsychiatric, physical, functional, and biomarker outcomes, along with actigraphy monitoring.
|
Niagen
n=37 Participants
Participants randomized to the Niagen group received NR (TruNiagen, Chromadex) 1000 mg twice daily for 20 weeks following a two-week placebo lead-in period. Dosing was double-blinded. Participants completed assessments of cognitive, neuropsychiatric, physical, functional, and biomarker outcomes, along with actigraphy monitoring.
|
Total
n=58 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
43.76 Years
STANDARD_DEVIATION 12.72 • n=5 Participants
|
47.05 Years
STANDARD_DEVIATION 13.79 • n=7 Participants
|
45.86 Years
STANDARD_DEVIATION 13.40 • n=5 Participants
|
|
Sex: Female, Male
Female
|
16 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
42 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
20 Participants
n=5 Participants
|
33 Participants
n=7 Participants
|
53 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
18 Participants
n=5 Participants
|
34 Participants
n=7 Participants
|
52 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
21 Participants
n=5 Participants
|
37 Participants
n=7 Participants
|
58 Participants
n=5 Participants
|
|
Education
High School/GED
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Education
Some College
|
1 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Education
Associate or Technical Degree
|
0 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Education
College
|
8 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
29 Participants
n=5 Participants
|
|
Education
Professional Studies
|
11 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 10 and Week 20Population: Only participants with complete outcome data at both timepoints relevant to a given change score were included in the analysis. Participants with missing data at either timepoint were excluded from the analysis for that specific outcome. As a result, the number of participants analyzed is lower than the total number randomized in each group.
Cognitive outcomes were assessed using the Everyday Cognition (ECog) scale, Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and the Trail Making Test B (TMT-B). The ECog total score ranges from 39 to 156, and individual domain scores range from 1 to 4. Higher scores indicate greater subjective cognitive decline since COVID-19 infection. Individual RBANS index scores range from 40 to 160, and the Sum of Index Scores (sum of five index scores) ranges from 200 to 800. Higher index scores reflect better cognitive performance. The TMT-B score is the completion time in seconds, with a maximum time of 5 minutes. A lower time is indicative of a better performance. Change scores reflect the difference from Baseline to Week 10, and from Week 10 to Week 20. Positive change scores on the ECog indicate worsening subjective cognitive decline. Positive change scores on the RBANS indicate improvement. Positive change scores in the TMT-B represent worsening performance.
Outcome measures
| Measure |
Niagen
n=29 Participants
Supplement: 60 participants will take Niagen 2000mg in the form of capsules daily.
Niagen: The intervention consists of taking Niagen and completing all tasks divided into 6 visits.
|
Placebo
n=21 Participants
Placebo: 40 participants will take placebo in the form of a capsule.
Niagen: The intervention consists of taking Niagen and completing all tasks divided into 6 visits.
|
|---|---|---|
|
Effect of Niagen on NAD+ and Cognitive Functioning
ECog Total (Baseline to Week 10)
|
-0.104 units on a scale
Standard Deviation 0.370
|
-0.214 units on a scale
Standard Deviation 0.370
|
|
Effect of Niagen on NAD+ and Cognitive Functioning
ECog Total (Week 10 to Week 20)
|
-0.014 units on a scale
Standard Deviation 0.548
|
-0.147 units on a scale
Standard Deviation 0.236
|
|
Effect of Niagen on NAD+ and Cognitive Functioning
ECog Memory (Baseline to Week 10)
|
-0.222 units on a scale
Standard Deviation 0.422
|
-0.285 units on a scale
Standard Deviation 0.564
|
|
Effect of Niagen on NAD+ and Cognitive Functioning
ECog Memory (Week 10 to Week 20)
|
0.068 units on a scale
Standard Deviation 0.515
|
-0.139 units on a scale
Standard Deviation 0.498
|
|
Effect of Niagen on NAD+ and Cognitive Functioning
ECog Language (Baseline to Week 10)
|
-0.216 units on a scale
Standard Deviation 0.415
|
-0.289 units on a scale
Standard Deviation 0.378
|
|
Effect of Niagen on NAD+ and Cognitive Functioning
ECog Language (Week 10 to Week 20)
|
0.068 units on a scale
Standard Deviation 0.528
|
-0.088 units on a scale
Standard Deviation 0.321
|
|
Effect of Niagen on NAD+ and Cognitive Functioning
ECog Visualspatial (Baseline to Week 10)
|
0.103 units on a scale
Standard Deviation 0.564
|
-0.203 units on a scale
Standard Deviation 0.460
|
|
Effect of Niagen on NAD+ and Cognitive Functioning
ECog Visualspatial (Week 10 to Week 20)
|
-0.132 units on a scale
Standard Deviation 0.878
|
-0.028 units on a scale
Standard Deviation 0.283
|
|
Effect of Niagen on NAD+ and Cognitive Functioning
ECog Planning (Baseline to Week 10)
|
-0.130 units on a scale
Standard Deviation 0.643
|
-0.211 units on a scale
Standard Deviation 0.478
|
|
Effect of Niagen on NAD+ and Cognitive Functioning
ECog Planning (Week 10 to Week 20)
|
0.081 units on a scale
Standard Deviation 0.642
|
-0.089 units on a scale
Standard Deviation 0.293
|
|
Effect of Niagen on NAD+ and Cognitive Functioning
ECog Organization (Baseline to Week 10)
|
0.060 units on a scale
Standard Deviation 1.014
|
-0.100 units on a scale
Standard Deviation 0.517
|
|
Effect of Niagen on NAD+ and Cognitive Functioning
ECog Organization (Week 10 to Week 20)
|
-0.179 units on a scale
Standard Deviation 1.072
|
-0.278 units on a scale
Standard Deviation 0.423
|
|
Effect of Niagen on NAD+ and Cognitive Functioning
ECog Attention (Baseline to Week 10)
|
-0.150 units on a scale
Standard Deviation 0.633
|
-0.139 units on a scale
Standard Deviation 0.479
|
|
Effect of Niagen on NAD+ and Cognitive Functioning
ECog Attention (Week 10 to Week 20)
|
-0.028 units on a scale
Standard Deviation 0.808
|
-0.347 units on a scale
Standard Deviation 0.486
|
|
Effect of Niagen on NAD+ and Cognitive Functioning
RBANS Sum of Index Scores (Baseline to Week 10)
|
10.600 units on a scale
Standard Deviation 29.819
|
10.000 units on a scale
Standard Deviation 23.314
|
|
Effect of Niagen on NAD+ and Cognitive Functioning
RBANS Sum of Index Scores (Week 10 to Week 20)
|
-8.111 units on a scale
Standard Deviation 26.169
|
-13.556 units on a scale
Standard Deviation 40.441
|
|
Effect of Niagen on NAD+ and Cognitive Functioning
RBANS Immediate Memory (Baseline to Week 10)
|
5.800 units on a scale
Standard Deviation 13.808
|
4.944 units on a scale
Standard Deviation 12.085
|
|
Effect of Niagen on NAD+ and Cognitive Functioning
RBANS Immediate Memory (Week 10 to Week 20)
|
-4.167 units on a scale
Standard Deviation 11.784
|
-6.389 units on a scale
Standard Deviation 13.954
|
|
Effect of Niagen on NAD+ and Cognitive Functioning
RBANS Delayed Memory (Baseline to Week 10)
|
4.920 units on a scale
Standard Deviation 11.420
|
2.167 units on a scale
Standard Deviation 9.787
|
|
Effect of Niagen on NAD+ and Cognitive Functioning
RBANS Delayed Memory (Week 10 to Week 20)
|
0.944 units on a scale
Standard Deviation 8.047
|
-3.111 units on a scale
Standard Deviation 12.925
|
|
Effect of Niagen on NAD+ and Cognitive Functioning
RBANS Attention (Baseline to Week 10)
|
4.080 units on a scale
Standard Deviation 11.358
|
5.333 units on a scale
Standard Deviation 12.825
|
|
Effect of Niagen on NAD+ and Cognitive Functioning
RBANS Attention (Week 10 to Week 20)
|
-2.056 units on a scale
Standard Deviation 12.822
|
-0.389 units on a scale
Standard Deviation 12.930
|
|
Effect of Niagen on NAD+ and Cognitive Functioning
RBANS Language (Baseline to Week 10)
|
-2.720 units on a scale
Standard Deviation 12.674
|
-0.222 units on a scale
Standard Deviation 15.653
|
|
Effect of Niagen on NAD+ and Cognitive Functioning
RBANS Language (Week 10 to Week 20)
|
-1.833 units on a scale
Standard Deviation 14.284
|
-3.556 units on a scale
Standard Deviation 16.639
|
|
Effect of Niagen on NAD+ and Cognitive Functioning
RBANS Visuospatial (Baseline to Week 10)
|
-1.560 units on a scale
Standard Deviation 13.058
|
-1.556 units on a scale
Standard Deviation 12.538
|
|
Effect of Niagen on NAD+ and Cognitive Functioning
RBANS Visuospatial (Week 10 to Week 20)
|
1.056 units on a scale
Standard Deviation 14.198
|
0.167 units on a scale
Standard Deviation 13.143
|
|
Effect of Niagen on NAD+ and Cognitive Functioning
Trail-Making-Test B (Baseline to Week 10)
|
-10.164 units on a scale
Standard Deviation 21.456
|
-6.574 units on a scale
Standard Deviation 14.272
|
|
Effect of Niagen on NAD+ and Cognitive Functioning
Trail-Making-Test B (Week 10 to Week 20)
|
-3.525 units on a scale
Standard Deviation 20.103
|
-5.856 units on a scale
Standard Deviation 19.148
|
SECONDARY outcome
Timeframe: Baseline, Week 10 and Week 20Population: Only participants with complete outcome data at both timepoints relevant to a given change score were included in the analysis. Participants with missing data at either timepoint were excluded from the analysis for that specific outcome. As a result, the number of participants analyzed is lower than the total number randomized in each group.
Depression symptoms were assessed using the Beck Depression Inventory (BDI), a 21-item self-report questionnaire measuring severity of depression symptoms. Total scores range from 0 to 63, with higher scores indicating more severe depression. Values represent mean change scores from Baseline to Week 10 and from Week 10 to Week 20.
Outcome measures
| Measure |
Niagen
n=29 Participants
Supplement: 60 participants will take Niagen 2000mg in the form of capsules daily.
Niagen: The intervention consists of taking Niagen and completing all tasks divided into 6 visits.
|
Placebo
n=21 Participants
Placebo: 40 participants will take placebo in the form of a capsule.
Niagen: The intervention consists of taking Niagen and completing all tasks divided into 6 visits.
|
|---|---|---|
|
Effect of Niagen on NAD+ and Depression Symptoms
BDI (Baseline to Week 10)
|
-1.360 score on a scale
Standard Deviation 5.529
|
0.167 score on a scale
Standard Deviation 5.659
|
|
Effect of Niagen on NAD+ and Depression Symptoms
BDI (Week 10 to Week 20)
|
0.167 score on a scale
Standard Deviation 4.301
|
-2.111 score on a scale
Standard Deviation 4.945
|
SECONDARY outcome
Timeframe: Baseline, Week 10 and Week 20Population: Only participants with complete outcome data at both timepoints relevant to a given change score were included in the analysis. Participants with missing data at either timepoint were excluded from the analysis for that specific outcome. As a result, the number of participants analyzed is lower than the total number randomized in each group.
Anxiety symptoms were assessed using the Beck Anxiety Inventory (BAI), a 21-item self-report questionnaire measuring severity of anxiety symptoms. Total scores range from 0 to 63, with higher scores indicating more severe anxiety. Values represent mean change scores from Baseline to Week 10 and from Week 10 to Week 20.
Outcome measures
| Measure |
Niagen
n=29 Participants
Supplement: 60 participants will take Niagen 2000mg in the form of capsules daily.
Niagen: The intervention consists of taking Niagen and completing all tasks divided into 6 visits.
|
Placebo
n=21 Participants
Placebo: 40 participants will take placebo in the form of a capsule.
Niagen: The intervention consists of taking Niagen and completing all tasks divided into 6 visits.
|
|---|---|---|
|
Effect of Niagen on NAD+ and Anxiety Symptoms
BAI (Baseline to Week 10)
|
-0.840 score on a scale
Standard Deviation 7.301
|
-1.333 score on a scale
Standard Deviation 6.589
|
|
Effect of Niagen on NAD+ and Anxiety Symptoms
BAI (Week 10 to Week 20)
|
-0.167 score on a scale
Standard Deviation 5.628
|
-1.778 score on a scale
Standard Deviation 4.387
|
SECONDARY outcome
Timeframe: Baseline, Week 10 and Week 20Population: Only participants with complete outcome data at both timepoints relevant to a given change score were included in the analysis. Participants with missing data at either timepoint were excluded from the analysis for that specific outcome. As a result, the number of participants analyzed is lower than the total number randomized in each group.
Fatigue was assessed using the Fatigue Severity Scale (FSS), a 9-item self-report measure with scores ranging from 1 to 7; higher scores indicate greater fatigue severity. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI), a 19-item self-report measure with scores ranging from 0 to 21; higher scores indicate poorer sleep quality. All values represent mean change scores from Baseline to Week 10 and from Week 10 to Week 20.
Outcome measures
| Measure |
Niagen
n=29 Participants
Supplement: 60 participants will take Niagen 2000mg in the form of capsules daily.
Niagen: The intervention consists of taking Niagen and completing all tasks divided into 6 visits.
|
Placebo
n=21 Participants
Placebo: 40 participants will take placebo in the form of a capsule.
Niagen: The intervention consists of taking Niagen and completing all tasks divided into 6 visits.
|
|---|---|---|
|
Effect of Niagen on NAD+ and Other COVID-related Symptoms
FSS Total Fatigue (Baseline to Week 10)
|
-3.400 score on a scale
Standard Deviation 7.708
|
-0.389 score on a scale
Standard Deviation 8.417
|
|
Effect of Niagen on NAD+ and Other COVID-related Symptoms
FSS Total Fatigue (Week 10 to Week 20)
|
3.444 score on a scale
Standard Deviation 9.083
|
-4.278 score on a scale
Standard Deviation 4.775
|
Adverse Events
Lead in
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 19 other events
Deaths: 0 deaths
Niagen
Serious events: 1 serious events
Other events: 25 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Lead in
n=72 participants at risk
Participants assigned to the Lead-in Phase received placebo capsules at the screening visit and were instructed to take four capsules in the morning and four capsules in the evening (8 capsules daily) for two weeks. All capsules were visually identical to the active study drug and were administered using the same dosing instructions as those in the randomized phase.
|
Placebo
n=21 participants at risk
Participants randomized to the Placebo group took four capsules in the morning and four capsules in the evening (8 capsules daily) for 10 weeks following a two-week placebo lead-in period. After the initial 10 weeks, participants crossed over to receive 1000 mg of NR (Niagen) twice daily for an additional 10 weeks. Dosing was double-blinded. Participants completed clinical assessments and cognitive testing at baseline, Visit 2, and Visit 4, and provided blood at every visit since baseline.
|
Niagen
n=37 participants at risk
Participants randomized to the NR group received 1000 mg of NR (Niagen) twice daily for 20 weeks following a two-week placebo lead-in period. Dosing was double-blinded. Participants completed clinical assessments and cognitive testing at baseline, Visit 2, and Visit 4, and provided blood at every visit since baseline.
|
|---|---|---|---|
|
Psychiatric disorders
Suicidal ideation
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
0.00%
0/21 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
2.7%
1/37 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
Other adverse events
| Measure |
Lead in
n=72 participants at risk
Participants assigned to the Lead-in Phase received placebo capsules at the screening visit and were instructed to take four capsules in the morning and four capsules in the evening (8 capsules daily) for two weeks. All capsules were visually identical to the active study drug and were administered using the same dosing instructions as those in the randomized phase.
|
Placebo
n=21 participants at risk
Participants randomized to the Placebo group took four capsules in the morning and four capsules in the evening (8 capsules daily) for 10 weeks following a two-week placebo lead-in period. After the initial 10 weeks, participants crossed over to receive 1000 mg of NR (Niagen) twice daily for an additional 10 weeks. Dosing was double-blinded. Participants completed clinical assessments and cognitive testing at baseline, Visit 2, and Visit 4, and provided blood at every visit since baseline.
|
Niagen
n=37 participants at risk
Participants randomized to the NR group received 1000 mg of NR (Niagen) twice daily for 20 weeks following a two-week placebo lead-in period. Dosing was double-blinded. Participants completed clinical assessments and cognitive testing at baseline, Visit 2, and Visit 4, and provided blood at every visit since baseline.
|
|---|---|---|---|
|
Skin and subcutaneous tissue disorders
Acne
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
4.8%
1/21 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
2.7%
1/37 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Immune system disorders
Allergic reaction
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
0.00%
0/21 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
5.4%
2/37 • Number of events 2 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Musculoskeletal and connective tissue disorders
Arm pain
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
0.00%
0/21 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
2.7%
1/37 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Musculoskeletal and connective tissue disorders
Back spasm
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
0.00%
0/21 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
2.7%
1/37 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Infections and infestations
Bronchitis
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
4.8%
1/21 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
0.00%
0/37 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Injury, poisoning and procedural complications
Brusing
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
4.8%
1/21 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
0.00%
0/37 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Injury, poisoning and procedural complications
Burn
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
0.00%
0/21 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
2.7%
1/37 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Cardiac disorders
Chest pain
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
0.00%
0/21 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
2.7%
1/37 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Vascular disorders
Cold hands
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
4.8%
1/21 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
0.00%
0/37 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
General disorders
Cold Sweats
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
4.8%
1/21 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
0.00%
0/37 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Eye disorders
Conjunctivitis
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
4.8%
1/21 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
0.00%
0/37 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
4.8%
1/21 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
2.7%
1/37 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Infections and infestations
COVID-19 infection
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
4.8%
1/21 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
10.8%
4/37 • Number of events 4 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
4.8%
1/21 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
2.7%
1/37 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Nervous system disorders
Dizziness
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
4.8%
1/21 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
2.7%
1/37 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
0.00%
0/21 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
2.7%
1/37 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Vascular disorders
Edema of hand
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
0.00%
0/21 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
2.7%
1/37 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Vascular disorders
Edema of leg
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
0.00%
0/21 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
2.7%
1/37 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Vascular disorders
Facial flushing
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
0.00%
0/21 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
5.4%
2/37 • Number of events 2 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Nervous system disorders
Facial pain
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
0.00%
0/21 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
2.7%
1/37 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
4.8%
1/21 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
2.7%
1/37 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Investigations
Falx cerebri calcification
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
4.8%
1/21 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
0.00%
0/37 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Gastrointestinal disorders
GI discomfort
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
4.8%
1/21 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
10.8%
4/37 • Number of events 4 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Nervous system disorders
Hand trembling
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
0.00%
0/21 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
2.7%
1/37 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Nervous system disorders
Headache
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
9.5%
2/21 • Number of events 2 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
2.7%
1/37 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Gastrointestinal disorders
Heartburn
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
9.5%
2/21 • Number of events 2 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
0.00%
0/37 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Gastrointestinal disorders
Worsening IBS
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
0.00%
0/21 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
2.7%
1/37 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Gastrointestinal disorders
Increased eructation
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
4.8%
1/21 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
0.00%
0/37 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Infections and infestations
Infection
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
4.8%
1/21 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
0.00%
0/37 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Injury, poisoning and procedural complications
Injury
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
14.3%
3/21 • Number of events 3 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
0.00%
0/37 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Musculoskeletal and connective tissue disorders
Joint ache
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
4.8%
1/21 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
0.00%
0/37 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Renal and urinary disorders
Kidney stone
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
4.8%
1/21 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
0.00%
0/37 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Musculoskeletal and connective tissue disorders
Leg cramps
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
0.00%
0/21 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
5.4%
2/37 • Number of events 2 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Nervous system disorders
Lightheadedness
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
0.00%
0/21 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
2.7%
1/37 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Metabolism and nutrition disorders
Low vitamin B12
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
4.8%
1/21 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
0.00%
0/37 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Musculoskeletal and connective tissue disorders
Muscle cramps
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
4.8%
1/21 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
0.00%
0/37 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Musculoskeletal and connective tissue disorders
Muscle strain
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
9.5%
2/21 • Number of events 2 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
0.00%
0/37 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
9.5%
2/21 • Number of events 2 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
8.1%
3/37 • Number of events 3 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
General disorders
Night sweats
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
0.00%
0/21 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
2.7%
1/37 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Renal and urinary disorders
Nocturia
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
4.8%
1/21 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
0.00%
0/37 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Ear and labyrinth disorders
Otitis media
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
0.00%
0/21 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
2.7%
1/37 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Nervous system disorders
Paresthesia in extremities
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
0.00%
0/21 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
2.7%
1/37 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Vascular disorders
Paroxysmal blood pressure
|
1.4%
1/72 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
0.00%
0/21 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
0.00%
0/37 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Investigations
Pineal cyst
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
0.00%
0/21 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
2.7%
1/37 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
0.00%
0/21 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
5.4%
2/37 • Number of events 2 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
0.00%
0/21 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
10.8%
4/37 • Number of events 4 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Infections and infestations
Sinus infection
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
4.8%
1/21 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
2.7%
1/37 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Nervous system disorders
Restless leg
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
0.00%
0/21 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
2.7%
1/37 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Musculoskeletal and connective tissue disorders
Stiffness in finger
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
4.8%
1/21 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
0.00%
0/37 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Infections and infestations
Upper respiratory infection
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
19.0%
4/21 • Number of events 4 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
16.2%
6/37 • Number of events 7 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Renal and urinary disorders
Urine odor
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
0.00%
0/21 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
2.7%
1/37 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Reproductive system and breast disorders
Vaginal bleeding
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
0.00%
0/21 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
2.7%
1/37 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Nervous system disorders
Vertigo
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
4.8%
1/21 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
5.4%
2/37 • Number of events 2 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Infections and infestations
Viral syndrome
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
0.00%
0/21 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
2.7%
1/37 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Gastrointestinal disorders
Worsening bile reflux
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
4.8%
1/21 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
0.00%
0/37 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Respiratory, thoracic and mediastinal disorders
Worsening cough
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
4.8%
1/21 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
0.00%
0/37 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Psychiatric disorders
Worsening insomina
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
0.00%
0/21 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
5.4%
2/37 • Number of events 2 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
|
Psychiatric disorders
Worsening sleep
|
0.00%
0/72 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
4.8%
1/21 • Number of events 1 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
5.4%
2/37 • Number of events 2 • Adverse events were systematically collected at every visit, for a total of 24 weeks.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place