Nicotinamide Riboside for Treating Elevated Systolic Blood Pressure and Arterial Stiffness in Middle-aged and Older Adults
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03821623|
Recruitment Status : Recruiting
First Posted : January 30, 2019
Last Update Posted : April 22, 2019
Aging is the primary risk factor for cardiovascular diseases (CVD), the number one cause of death in developed societies. Systolic blood pressure (SBP) increase with age and is a key intermediary factor linking aging to increased CVD risk. The primary mechanisms underlying the age-associated increase in SBP is stiffening of the large elastic arteries, which is mediated by increases in oxidative stress, inflammation, and vascular smooth muscle tone. Regular caloric restriction is effective at lowering SBP in middle-aged and older adults; however, adherence to caloric restriction is poor and may be detrimental to normal weight older adults due to reduced skeletal muscle mass and bone mineral density. Therefore, identification of more practical alternative interventions that mimic the beneficial effects of caloric restriction, with stronger adherence and less risk of adverse consequences, is of significant biomedical importance.
Nicotinamide riboside is a naturally occurring precursor of nicotinamide adenine dinucleotide (NAD+), a critical mediator of the beneficial effects of caloric restriction, and therefore a novel caloric restriction mimetic compound. We recently completed the first pilot study of nicotinamide riboside supplementation in healthy middle-aged and older adults and demonstrated that 6 weeks of supplementation decreased systolic blood pressure (SBP) by 8 mmHg in individuals with baseline SBP of 120-139 mmHg (elevated SBP/stage 1 hypertension) compared with placebo, and lowered arterial stiffness, a strong independent predictor of CVD and related morbidity and mortality.
As a next translational step, we will conduct a randomized, placebo-controlled, double-blind clinical trial to further assess the safety and efficacy of oral nicotinamide riboside (3 months vs placebo) for decreasing SBP and arterial stiffness in middle-aged and older men and women with SBP between 120 and 139 mmHg at baseline.
|Condition or disease||Intervention/treatment||Phase|
|Hypertension Aging||Drug: Nicotinamide riboside Other: Placebo||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||118 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Investigator, Outcomes Assessor)|
|Official Title:||Nicotinamide Riboside Supplementation for Treating Elevated Systolic Blood Pressure and Arterial Stiffness in Middle-aged and Older Adults|
|Actual Study Start Date :||April 18, 2019|
|Estimated Primary Completion Date :||December 2023|
|Estimated Study Completion Date :||December 2023|
Experimental: Nicotinamide riboside
Subjects will take 500 mg of the vitamin B3-precursor, nicotinamide riboside (NIAGEN) twice per day (1,000 mg per day total) for 3 months.
Drug: Nicotinamide riboside
Nicotinamide riboside, a dietary supplement available over the counter under the name NIAGEN®, (ChromaDex Inc) is an exogenous NAD+ precursor that reverses age-related arterial dysfunction in aged mice, suggesting that declining NAD+ may play a key role in cardiovascular aging.
Placebo Comparator: Placebo
Subjects will take placebo pills twice a day for 3 months.
Subjects will take placebo pills twice a day for 3 months
- Systolic blood pressure [ Time Frame: 3 months ]Resting systolic blood pressure
- Ambulatory blood pressure [ Time Frame: 3 months ]24-hour mean blood pressure
- Arterial stiffness [ Time Frame: 3 months ]Carotid-femoral pulse wave velocity
- Number and severity of adverse events (safety) [ Time Frame: 3 months ]Monitoring and documentation of number and type of adverse events
- Number of participants that dropout due to adverse events (tolerability) [ Time Frame: 3 months ]Monitoring subject dropout due to adverse events
- Adherence to the intervention (percentage of prescribed pills consumed) [ Time Frame: 3 months ]Counting returned pills on a bi-weekly basis to determine what percentage of prescribed pills subjects take.
- NAD+ and related metabolite blood levels [ Time Frame: 3 months ]Blood samples will be analysed using high performance liquid chromatography-mass spectronomy analysis for levels of NAD+ and related metabolites including: NADP+, nicotinic acid adeniene dinucleotide, nicotinamide, and nicotinamide mononucleotide.
- Sympathetic activity [ Time Frame: 3 months ]Plasma norepinephrine, a marker of sympathetic activity, will be measured by high performance liquid chromatography
- Oxidative stress [ Time Frame: 3 months ]Plasma oxidized LDL, a marker of oxidative stress, will be measured by ELISA
- Inflammation [ Time Frame: 3 months ]Plasma interleukin-6, a marker of inflammation, will be measured by ELISA
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03821623
|Contact: Daniel H Craighead, PhDemail@example.com|
|United States, Colorado|
|Integrative Physiology of Aging Laboratory||Recruiting|
|Boulder, Colorado, United States, 80309|
|Contact: Melanie R Zigler, MS 303-492-2485 firstname.lastname@example.org|
|Principal Investigator: Douglas R Seals, PhD|