Trial Outcomes & Findings for Nicotinamide Riboside as an Enhancer of Exercise Therapy in Hypertensive Older Adults (The NEET Trial) (NCT NCT04112043)

NCT ID: NCT04112043

Last Updated: 2024-06-06

Results Overview

The primary outcome of this study is the change in average daytime systolic blood pressure. Systolic blood pressure was measured every 20 minutes (min) during the day (from 0700 to 2200 hours) at baseline and week 6 visits. Based on the American Heart Association guideline, we selected twenty valid daytime blood pressure recordings to calculate the average daytime value, then we calculated the mean differences between week 6 and baseline.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

147 participants

Primary outcome timeframe

Baseline; Week 6

Results posted on

2024-06-06

Participant Flow

Of 147 enrolled participants, 54 met the eligible criteria and were randomized to treatment.

Participant milestones

Participant milestones
Measure	NR Plus Walking Exercise 1,000 mg/day of NR combined with three days/week of supervised, center-based walking exercise (n=18) Walking Exercise: Participants randomized to this intervention 3 days/week of supervised, center-based walking exercise. Nicotinamide Riboside (NR): Participants randomized to this intervention will receive 1,000 mg/day of NR.	Walking Exercise Plus Placebo 1,000 mg/day of Placebo combined with three days/week of supervised, center-based walking exercise (n=18) Walking Exercise: Participants randomized to this intervention 3 days/week of supervised, center-based walking exercise.	NR Alone 1,000 mg/day of NR Nicotinamide Riboside (NR): Participants randomized to this intervention will receive 1,000 mg/day of NR.
Overall Study STARTED	17	18	19
Overall Study COMPLETED	15	16	18
Overall Study NOT COMPLETED	2	2	1

Reasons for withdrawal

Reasons for withdrawal
Measure	NR Plus Walking Exercise 1,000 mg/day of NR combined with three days/week of supervised, center-based walking exercise (n=18) Walking Exercise: Participants randomized to this intervention 3 days/week of supervised, center-based walking exercise. Nicotinamide Riboside (NR): Participants randomized to this intervention will receive 1,000 mg/day of NR.	Walking Exercise Plus Placebo 1,000 mg/day of Placebo combined with three days/week of supervised, center-based walking exercise (n=18) Walking Exercise: Participants randomized to this intervention 3 days/week of supervised, center-based walking exercise.	NR Alone 1,000 mg/day of NR Nicotinamide Riboside (NR): Participants randomized to this intervention will receive 1,000 mg/day of NR.
Overall Study Withdrawal by Subject	1	1	1
Overall Study Taking NR supplement	1	0	0
Overall Study Adverse Event	0	1	0

Baseline Characteristics

Average daytime systolic blood pressure was calculated based on all the available daytime blood pressure readings recorded by the 24-hour ambulatory blood pressure monitor.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	NR Plus Walking Exercise n=17 Participants 1,000 mg/day of NR combined with three days/week of supervised, center-based walking exercise (n=18) Walking Exercise: Participants randomized to this intervention 3 days/week of supervised, center-based walking exercise. Nicotinamide Riboside (NR): Participants randomized to this intervention will receive 1,000 mg/day of NR.	Walking Exercise Plus Placebo n=18 Participants 1,000 mg/day of Placebo combined with three days/week of supervised, center-based walking exercise (n=18) Walking Exercise: Participants randomized to this intervention 3 days/week of supervised, center-based walking exercise.	NR Alone n=19 Participants 1,000 mg/day of NR Nicotinamide Riboside (NR): Participants randomized to this intervention will receive 1,000 mg/day of NR.	Total n=54 Participants Total of all reporting groups
Age, Continuous	67.5 years STANDARD_DEVIATION 7.0 • n=5 Participants	68.3 years STANDARD_DEVIATION 7.7 • n=7 Participants	66.3 years STANDARD_DEVIATION 7.2 • n=5 Participants	67.3 years STANDARD_DEVIATION 7.3 • n=4 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	10 Participants n=7 Participants	12 Participants n=5 Participants	33 Participants n=4 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	8 Participants n=7 Participants	7 Participants n=5 Participants	21 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 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	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants	15 Participants n=4 Participants
Race (NIH/OMB) White	12 Participants n=5 Participants	13 Participants n=7 Participants	11 Participants n=5 Participants	36 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment United States	17 Participants n=5 Participants	18 Participants n=7 Participants	19 Participants n=5 Participants	54 Participants n=4 Participants
Body Mass Index	33.0 kg/m^2 STANDARD_DEVIATION 7.2 • n=5 Participants	30.8 kg/m^2 STANDARD_DEVIATION 5.7 • n=7 Participants	30.7 kg/m^2 STANDARD_DEVIATION 7.8 • n=5 Participants	31.5 kg/m^2 STANDARD_DEVIATION 6.9 • n=4 Participants
Baseline average daytime systolic blood pressure	138.5 mmHg STANDARD_DEVIATION 11.8 • n=5 Participants • Average daytime systolic blood pressure was calculated based on all the available daytime blood pressure readings recorded by the 24-hour ambulatory blood pressure monitor.	141 mmHg STANDARD_DEVIATION 12.1 • n=7 Participants • Average daytime systolic blood pressure was calculated based on all the available daytime blood pressure readings recorded by the 24-hour ambulatory blood pressure monitor.	138.8 mmHg STANDARD_DEVIATION 14.9 • n=5 Participants • Average daytime systolic blood pressure was calculated based on all the available daytime blood pressure readings recorded by the 24-hour ambulatory blood pressure monitor.	139.4 mmHg STANDARD_DEVIATION 12.8 • n=4 Participants • Average daytime systolic blood pressure was calculated based on all the available daytime blood pressure readings recorded by the 24-hour ambulatory blood pressure monitor.
Baseline average daytime diastolic blood pressure	75.5 mmHg STANDARD_DEVIATION 8.6 • n=5 Participants • Average daytime diastolic blood pressure was calculated based on all the available daytime blood pressure readings recorded by the 24-hour ambulatory blood pressure monitor.	75.2 mmHg STANDARD_DEVIATION 6.5 • n=7 Participants • Average daytime diastolic blood pressure was calculated based on all the available daytime blood pressure readings recorded by the 24-hour ambulatory blood pressure monitor.	78.2 mmHg STANDARD_DEVIATION 10.2 • n=5 Participants • Average daytime diastolic blood pressure was calculated based on all the available daytime blood pressure readings recorded by the 24-hour ambulatory blood pressure monitor.	76.3 mmHg STANDARD_DEVIATION 8.5 • n=4 Participants • Average daytime diastolic blood pressure was calculated based on all the available daytime blood pressure readings recorded by the 24-hour ambulatory blood pressure monitor.

PRIMARY outcome

Timeframe: Baseline; Week 6

Population: Considering within-group differences for interested variables; we focus on the mean differences between week 6 and the baseline.

Outcome measures

Outcome measures
Measure	NR Plus Walking Exercise n=15 Participants 1,000 mg/day of NR combined with three days/week of supervised, center-based walking exercise (n=18) Walking Exercise: Participants randomized to this intervention 3 days/week of supervised, center-based walking exercise. Nicotinamide Riboside (NR): Participants randomized to this intervention will receive 1,000 mg/day of NR.	Walking Exercise Plus Placebo n=16 Participants 1,000 mg/day of Placebo combined with three days/week of supervised, center-based walking exercise (n=18) Walking Exercise: Participants randomized to this intervention 3 days/week of supervised, center-based walking exercise.	NR Alone n=17 Participants 1,000 mg/day of NR Nicotinamide Riboside (NR): Participants randomized to this intervention will receive 1,000 mg/day of NR.
Change in Daytime Systolic Blood Pressure	5.19 mmHg Interval -2.16 to 12.54	-2.71 mmHg Interval -8.29 to 2.87	-0.48 mmHg Interval -4.85 to 3.89

SECONDARY outcome

Timeframe: Baseline; Week 6

Population: Considering within-group differences for interested variables; we focus on the mean differences between week 6 and the baseline.

The measurement of aortic pulse-wave velocity (PWV), particularly between the carotid and femoral arteries (cfPWV), was conducted using the SphygmoCor XCEL system. Briefly, cfPWV was determined by recording pressure pulse waves at the carotid and femoral arteries using a high-fidelity micromanometer and calculating the distance between the recording sites divided by the time delay between the carotid and the femoral pulse waves.

Outcome measures

Outcome measures
Measure	NR Plus Walking Exercise n=14 Participants 1,000 mg/day of NR combined with three days/week of supervised, center-based walking exercise (n=18) Walking Exercise: Participants randomized to this intervention 3 days/week of supervised, center-based walking exercise. Nicotinamide Riboside (NR): Participants randomized to this intervention will receive 1,000 mg/day of NR.	Walking Exercise Plus Placebo n=15 Participants 1,000 mg/day of Placebo combined with three days/week of supervised, center-based walking exercise (n=18) Walking Exercise: Participants randomized to this intervention 3 days/week of supervised, center-based walking exercise.	NR Alone n=16 Participants 1,000 mg/day of NR Nicotinamide Riboside (NR): Participants randomized to this intervention will receive 1,000 mg/day of NR.
Change in Arterial Stiffness	-0.29 m/s Interval -0.74 to 0.17	-0.15 m/s Interval -0.59 to 0.29	-0.10 m/s Interval -0.56 to 0.37

Adverse Events

NR Plus Walking Exercise

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Walking Exercise Plus Placebo

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

NR Alone

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	NR Plus Walking Exercise n=17 participants at risk 1,000 mg/day of NR combined with three days/week of supervised, center-based walking exercise (n=18) Walking Exercise: Participants randomized to this intervention 3 days/week of supervised, center-based walking exercise. Nicotinamide Riboside (NR): Participants randomized to this intervention will receive 1,000 mg/day of NR.	Walking Exercise Plus Placebo n=18 participants at risk 1,000 mg/day of Placebo combined with three days/week of supervised, center-based walking exercise (n=18) Walking Exercise: Participants randomized to this intervention 3 days/week of supervised, center-based walking exercise.	NR Alone n=19 participants at risk 1,000 mg/day of NR Nicotinamide Riboside (NR): Participants randomized to this intervention will receive 1,000 mg/day of NR.
Infections and infestations Sepsis and Pneumonia	0.00% 0/17 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.	0.00% 0/18 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.	5.3% 1/19 • Number of events 1 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.

Other adverse events

Additional Information

Dr. Robert Mankowski

University of Florida

Phone: 352-294-5055

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	NR Plus Walking Exercise n=17 participants at risk 1,000 mg/day of NR combined with three days/week of supervised, center-based walking exercise (n=18) Walking Exercise: Participants randomized to this intervention 3 days/week of supervised, center-based walking exercise. Nicotinamide Riboside (NR): Participants randomized to this intervention will receive 1,000 mg/day of NR.	Walking Exercise Plus Placebo n=18 participants at risk 1,000 mg/day of Placebo combined with three days/week of supervised, center-based walking exercise (n=18) Walking Exercise: Participants randomized to this intervention 3 days/week of supervised, center-based walking exercise.	NR Alone n=19 participants at risk 1,000 mg/day of NR Nicotinamide Riboside (NR): Participants randomized to this intervention will receive 1,000 mg/day of NR.
Blood and lymphatic system disorders Pancytopenia Worsening	5.9% 1/17 • Number of events 1 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.	0.00% 0/18 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.	0.00% 0/19 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.
Gastrointestinal disorders Felt "spasm" feeling in the stomach	0.00% 0/17 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.	5.6% 1/18 • Number of events 1 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.	0.00% 0/19 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.
General disorders Headaches, loose stool, dry mouth and nose, fatigue	5.9% 1/17 • Number of events 1 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.	0.00% 0/18 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.	0.00% 0/19 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.
Metabolism and nutrition disorders High blood sugar	0.00% 0/17 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.	0.00% 0/18 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.	5.3% 1/19 • Number of events 1 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.
General disorders High PSA , high creatinine, frequent urination, increased hunger	0.00% 0/17 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.	0.00% 0/18 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.	5.3% 1/19 • Number of events 1 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.
Nervous system disorders Sciatic Nerve Pain	5.9% 1/17 • Number of events 1 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.	0.00% 0/18 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.	0.00% 0/19 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.
Musculoskeletal and connective tissue disorders Knee Pain	11.8% 2/17 • Number of events 2 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.	5.6% 1/18 • Number of events 1 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.	0.00% 0/19 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.
Musculoskeletal and connective tissue disorders Hurt Foot/Leg at Home	0.00% 0/17 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.	5.6% 1/18 • Number of events 1 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.	0.00% 0/19 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.
Musculoskeletal and connective tissue disorders Soreness from Exercise	0.00% 0/17 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.	5.6% 1/18 • Number of events 1 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.	0.00% 0/19 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.
Respiratory, thoracic and mediastinal disorders Symptoms (difficulty breathing, headache, etc.) due to COVID-19	0.00% 0/17 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.	5.6% 1/18 • Number of events 1 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.	5.3% 1/19 • Number of events 1 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.
Respiratory, thoracic and mediastinal disorders Allergies Became Worse	0.00% 0/17 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.	0.00% 0/18 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.	5.3% 1/19 • Number of events 1 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.
Musculoskeletal and connective tissue disorders Tripped and fell	0.00% 0/17 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.	11.1% 2/18 • Number of events 2 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.	0.00% 0/19 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.
Respiratory, thoracic and mediastinal disorders Cold or flu with symptoms (sneezing, runny nose, congestion, etc.)	0.00% 0/17 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.	5.6% 1/18 • Number of events 1 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.	5.3% 1/19 • Number of events 1 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.
Cardiac disorders Irregular Heartbeat	0.00% 0/17 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.	5.6% 1/18 • Number of events 1 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.	0.00% 0/19 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.
Metabolism and nutrition disorders Change in diabetes symptoms	0.00% 0/17 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.	5.6% 1/18 • Number of events 1 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.	0.00% 0/19 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.
Infections and infestations UTI	5.9% 1/17 • Number of events 1 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.	0.00% 0/18 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.	0.00% 0/19 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.
Surgical and medical procedures Cyst removal	5.9% 1/17 • Number of events 1 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.	0.00% 0/18 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.	0.00% 0/19 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.
Skin and subcutaneous tissue disorders Itching	0.00% 0/17 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.	0.00% 0/18 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.	5.3% 1/19 • Number of events 1 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.
Renal and urinary disorders Bloody Urine	0.00% 0/17 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.	0.00% 0/18 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.	5.3% 1/19 • Number of events 1 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.
General disorders Dizziness	0.00% 0/17 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.	5.6% 1/18 • Number of events 1 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.	0.00% 0/19 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.
Respiratory, thoracic and mediastinal disorders Sinus problems	5.9% 1/17 • Number of events 1 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.	0.00% 0/18 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.	0.00% 0/19 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.
Musculoskeletal and connective tissue disorders Upper back pain	5.9% 1/17 • Number of events 1 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.	0.00% 0/18 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.	0.00% 0/19 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.
Skin and subcutaneous tissue disorders Annoying feeling at the bottom of both feet due to calluses	0.00% 0/17 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.	5.6% 1/18 • Number of events 1 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.	0.00% 0/19 • 6 weeks We collected adverse events at baseline, 3-week visits, 6-week visits, and every exercise session.