Hypertension (HTN)
Conditions
Brief summary
Hypertension continues to pose a significant global health challenge, with rates of optimal blood pressure control remaining low - particularly in China, where fewer than 5% of individuals with hypertension achieve guideline-recommended targets. Age-associated endothelial dysfunction and arterial stiffness are recognized as the key contributors to the development of hypertension and the unique role of nicotinamide adenine dinucleotide (NAD) depletion in the pathogenesis of vascular dysfunction has been recently discovered. Treatment with nicotinamide riboside (NR), an NAD precursor, has shown promise in preliminary clinical trials for improving blood pressure and vascular health in at-risk populations. In parallel, aerobic exercise is a well-established non-pharmacologic intervention known to improve cardiovascular outcomes. Emerging studies suggest that exercise may modulate NAD biosynthesis pathways, pointing toward a synergistic potential when combined with NAD-boosting strategies. However, clinical data evaluating the combined effects of NR supplementation and aerobic exercise remain scarce. Our randomized, placebo-controlled, four-arm, parallel-group design seeks to address this gap. The investigators will investigate the independent and combined effects of 10-week NR supplementation and brisk walking on blood pressure and vascular health in post-menopausal women with elevated/stage I hypertension. This population is specifically targeted due to their heightened risk for vascular dysfunction post-menopause and the observed responsiveness to NR-based interventions in prior studies. The investigators believe the findings from this trial will provide insight into the feasibility, safety, and efficacy of combining NAD-boosting supplementation with structured exercise in a uniquely vulnerable and previously understudied population. The potential to identify a low-risk, non-pharmaceutical therapeutic approach holds strong implications for public health, particularly in aging women with early-stage hypertension.
Interventions
BEHAVIORALBrisk walking
Brisk walking twice per week
DIETARY_SUPPLEMENTNicotinamide Riboside 1000 mg
Nicotinamide Riboside supplementation 1000 mg per day
OTHERPlacebo
Placebo
Sponsors
ZHANG Jiaqi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
55 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* women absent of menstruation for over one year, * Chinese, and * fulfill the criteria of elevated/stage I hypertension according to 2025 American College of Cardiology/American Heart Association Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults (i.e., blood pressure ≥120/80 mmHg based on an average of ≥2 readings obtained on ≥2 occasions)
Exclusion criteria
* presence of health conditions that contraindicate participation in exercise training, such as a history of cardiovascular disease, cancer, or musculoskeletal disorders, * a history of hysterectomy, * current use of vitamin B supplements and/or NAD precursors, * ongoing hormone replacement therapy within the past six months, * any changes in antihypertensive medication type or dosage within the last three months, or * engagement in regular physical activity, defined as at least 150 minutes of moderate-intensity exercise or 75 minutes of vigorous-intensity exercise per week, during the three months prior to enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Blood pressure | From enrollment to the end of follow-up at 20 weeks | Blood pressure will be measured using an automated sphygmomanometer that meets the standards from the Association for the Advancement of Medical Instrumentation and the European Society for Hypertension and following standardized procedures. Two measurements will be taken after 5 min sitting rest in a quiet room with comfortable temperature. During assessments, participants will be seated with their back supported, feet flat on the floor, legs uncrossed, and their arm resting on a table with the midpoint of the upper arm aligned at heart level. Two readings of systolic and diastolic blood pressures will be obtained, spaced 2 minutes apart, and the average of the two measurements will be recorded as the final blood pressure reading. If the difference between the two measurements exceeds 5 mmHg, an additional reading will be taken, and the average of all three readings will be used as the final measurement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Whole Blood NAD concentration | From enrollment to the end of follow-up at 20 weeks | Whole blood NAD concentration will be analyzed with commercially available colorimetric assay kit according to manufacturer's instructions using thawed whole blood samples. |
| Endothelin 1 | From enrollment to the end of follow-up at 20 weeks | ET-1 will be analyzed with commercially available ELISA kit according to manufacturer's instructions using thawed serum samples and will serve as indicators of vascular function. |
| Angiotensin | From enrollment to the end of follow-up at 20 weeks | Angiotensin will be analyzed with commercially available ELISA kit according to manufacturer's instructions using thawed serum samples and will serve as indicators of vascular function. |
| Body mass | From enrollment to the end of follow-up at 20 weeks | Measured with bioelectrical impedance analysis (BIA) (MC-780 MA, Tanita, Japan) with participants in minimum clothing and normal hydration status. |
| Fat mass | From enrollment to the end of follow-up at 20 weeks | Measured with bioelectrical impedance analysis (BIA) (MC-780 MA, Tanita, Japan) with participants in minimum clothing and normal hydration status |
| Fat-free mass | From enrollment to the end of follow-up at 20 weeks | Measured with bioelectrical impedance analysis (BIA) (MC-780 MA, Tanita, Japan) with participants in minimum clothing and normal hydration status. |
| Fat percentage | From enrollment to the end of follow-up at 20 weeks | Measured with bioelectrical impedance analysis (BIA) (MC-780 MA, Tanita, Japan) with participants in minimum clothing and normal hydration status. |
| Height | From enrollment to the end of follow-up at 20 weeks | Measured using a stadiometer (Seca, Leicester, UK). |
| BMI | From enrollment to the end of follow-up at 20 weeks | Calculated as body mass (kg) divided by height squared (m2). |
| Waist Circumference | From enrollment to the end of follow-up at 20 weeks | Measured using anthropometric tape. |
| Seven-day accelerometry | From enrollment to the end of follow-up at 20 weeks | Participants will be instructed to wear a wrist accelerometer device on their non-dominant wrists 24 hours for 7 days to measure habitual physical activity pattern. Data will be downloaded and saved in raw format, then processed and analyzed with R-package GGIR. |
| 30-second chair stand test | From enrollment to the end of follow-up at 20 weeks | Muscle strength of the lower extremities will be assessed using the 30-second chair stand test. During the test, participants will be instructed to stand up to a full standing position and then sit back down as many times as possible within 30 seconds. The number of times participants achieve a full standing position will be recorded as their score. |
| Handgrip strength | From enrollment to the end of follow-up at 20 weeks | Measured using a hand-held dynamometer. |
Outcome results
None listed