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Nicotinamide Riboside for Treating Elevated Systolic Blood Pressure and Arterial Stiffness in Middle-aged and Older Adults

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ClinicalTrials.gov Identifier: NCT03821623
Recruitment Status : Not yet recruiting
First Posted : January 30, 2019
Last Update Posted : January 31, 2019
Sponsor:
Information provided by (Responsible Party):
Douglas Seals, University of Colorado, Boulder

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.


Condition or disease Intervention/treatment Phase
Hypertension Aging Drug: Nicotinamide riboside Other: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 118 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Nicotinamide Riboside Supplementation for Treating Elevated Systolic Blood Pressure and Arterial Stiffness in Middle-aged and Older Adults
Estimated Study Start Date : April 2019
Estimated Primary Completion Date : December 2023
Estimated Study Completion Date : December 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
Other: Placebo
Subjects will take placebo pills twice a day for 3 months




Primary Outcome Measures :
  1. Systolic blood pressure [ Time Frame: 3 months ]
    Resting systolic blood pressure


Secondary Outcome Measures :
  1. Ambulatory blood pressure [ Time Frame: 3 months ]
    24-hour mean blood pressure

  2. Arterial stiffness [ Time Frame: 3 months ]
    Carotid-femoral pulse wave velocity


Other Outcome Measures:
  1. Number and severity of adverse events (safety) [ Time Frame: 3 months ]
    Monitoring and documentation of number and type of adverse events

  2. Number of participants that dropout due to adverse events (tolerability) [ Time Frame: 3 months ]
    Monitoring subject dropout due to adverse events

  3. 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.

  4. 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.

  5. Sympathetic activity [ Time Frame: 3 months ]
    Plasma norepinephrine, a marker of sympathetic activity, will be measured by high performance liquid chromatography

  6. Oxidative stress [ Time Frame: 3 months ]
    Plasma oxidized LDL, a marker of oxidative stress, will be measured by ELISA

  7. Inflammation [ Time Frame: 3 months ]
    Plasma interleukin-6, a marker of inflammation, will be measured by ELISA



Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years to 79 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Ability to provide informed consent
  • Willing to accept random assignment to condition
  • Systolic blood pressure between 120 and 139 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

Exclusion Criteria:

  • Systolic blood pressure <120 or >/= 140 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)

Information from the National Library of Medicine

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


Contacts
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Contact: Daniel H Craighead, PhD 303-492-7702 daniel.craighead@colorado.edu

Locations
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United States, Colorado
Integrative Physiology of Aging Laboratory Not yet recruiting
Boulder, Colorado, United States, 80309
Contact: Melanie R Zigler, MS    303-492-2485    melanie.connell@colorado.edu   
Principal Investigator: Douglas R Seals, PhD         
Sponsors and Collaborators
Douglas Seals

Publications:
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Responsible Party: Douglas Seals, Principal Investigator, University of Colorado, Boulder
ClinicalTrials.gov Identifier: NCT03821623     History of Changes
Other Study ID Numbers: 18-0644
First Posted: January 30, 2019    Key Record Dates
Last Update Posted: January 31, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Niacinamide
Niacin
Nicotinic Acids
Vitamin B Complex
Vitamins
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Vasodilator Agents