NCT03821623

Brief Summary

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.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
118

participants targeted

Target at P50-P75 for phase_2 hypertension

Timeline
Completed

Started May 2019

Longer than P75 for phase_2 hypertension

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 14, 2019

Completed
16 days until next milestone

First Posted

Study publicly available on registry

January 30, 2019

Completed
3 months until next milestone

Study Start

First participant enrolled

May 10, 2019

Completed
6.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2025

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2025

Completed
Last Updated

February 21, 2025

Status Verified

February 1, 2025

Enrollment Period

6.1 years

First QC Date

January 14, 2019

Last Update Submit

February 19, 2025

Conditions

HypertensionAging

Outcome Measures

Primary Outcomes (1)

  • Systolic blood pressure

    Resting systolic blood pressure

    3 months

Secondary Outcomes (2)

  • Ambulatory blood pressure

    3 months

  • Arterial stiffness

    3 months

Other Outcomes (7)

  • Number and severity of adverse events (safety)

    3 months

  • Number of participants that dropout due to adverse events (tolerability)

    3 months

  • Adherence to the intervention (percentage of prescribed pills consumed)

    3 months

  • +4 more other outcomes

Study Arms (2)

Nicotinamide riboside

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

Subjects will take placebo pills twice a day for 3 months.

Other: Placebo

Interventions

Nicotinamide ribosideDRUG

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.

Nicotinamide riboside
PlaceboOTHER

Subjects will take placebo pills twice a day for 3 months

Placebo

Eligibility Criteria

Age50 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Ability to provide informed consent
  • Willing to accept random assignment to condition
  • Systolic blood pressure between 120 and 159 mmHg
  • Body mass index \<40 kg/m2
  • Weight stable in the prior 3 months (\<2 kg weight change) and willing to remain weight stable throughout the study
  • Absence of other clinical disease as determined by medical history, physical examination, blood chemistries, ankle-brachial index, and 12-lead ECG at rest and during graded treadmill exercise
  • Ankle-brachial index \>0.7
  • Total cholesterol \<240 mg/dL
  • Fasting plasma glucose \<126 mg/dL
  • Normal 12-lead ECG at rest and during graded treadmill exercise to fatigue

You may not qualify if:

  • Systolic blood pressure \<120 or \>/= 160 mmHg
  • Currently taking antihypertensive medications
  • Other chronic medical condition (e.g., diabetes, chronic kidney disease, cancer)
  • Current smoker
  • Alcohol dependence or abuse
  • Uncontrolled thyroid disease or change in thyroid medication within previous 3 months
  • Abnormal blood pressure response to exercise (drop in SBP below resting pressure or SBP \>160 mmHg or DBP \>115 mmHg)
  • Regular vigorous aerobic/endurance exercise (\>4 bouts/weeks, \>30 min/bout at a workload \>6 METS)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Integrative Physiology of Aging Laboratory

Boulder, Colorado, 80309, United States

RECRUITING

Related Publications (3)

  • Martens CR, Denman BA, Mazzo MR, Armstrong ML, Reisdorph N, McQueen MB, Chonchol M, Seals DR. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nat Commun. 2018 Mar 29;9(1):1286. doi: 10.1038/s41467-018-03421-7.

    PMID: 29599478BACKGROUND

  • Oh ES, Opoku G, Darvish S, Craighead DH, Ostrow A, Rossman MJ, Steele CN, Struemph T, You Z, Seals DR, Chonchol M, Nowak KL. Sex Differences in Dementia and Mild Cognitive Impairment in Nondialysis CKD. Clin J Am Soc Nephrol. 2025 Nov 20. doi: 10.2215/CJN.0000000922. Online ahead of print. No abstract available.

    PMID: 41264372DERIVED

  • Freeberg KA, Craighead DH, Martens CR, You Z, Chonchol M, Seals DR. Nicotinamide Riboside Supplementation for Treating Elevated Systolic Blood Pressure and Arterial Stiffness in Midlife and Older Adults. Front Cardiovasc Med. 2022 May 10;9:881703. doi: 10.3389/fcvm.2022.881703. eCollection 2022.

    PMID: 35620522DERIVED

MeSH Terms

Conditions

Hypertension

Interventions

nicotinamide-beta-riboside

Condition Hierarchy (Ancestors)

Vascular DiseasesCardiovascular Diseases

Central Study Contacts

Daniel H Craighead, PhD

CONTACT

303-492-7702daniel.craighead@colorado.edu

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

January 14, 2019

First Posted

January 30, 2019

Study Start

May 10, 2019

Primary Completion

June 1, 2025

Study Completion

June 1, 2025

Last Updated

February 21, 2025

Record last verified: 2025-02

Data Sharing

IPD Sharing
Will not share

Locations

US(1)