Nitrite Supplementation for Improving Physiological Function in Older Adults

NCT02393742 | Completed

• 1 other identifier: R01AG013038-19
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

Brief Summary

Nitric oxide (NO) is an essential molecule in the body that decreases with aging and causes reductions in vascular, movement ("motor") and cognitive functions. This study will determine if daily oral supplementation (3 months) with a compound that increases NO in the body, i.e., sodium nitrite, improves vascular, motor and cognitive function in older adults. The project also seeks to provide insight into the biological reasons (mechanisms) by which supplementation with sodium nitrite improves physiological function in older adults. Overall, this research will provide scientific evidence supporting the use of sodium nitrite for preserving physiological function and preventing clinical disease and disability with aging.

Conditions

Ageing

Outcome Measures

Primary Outcomes (2)

• Vascular Function

  flow mediated dilation

  3 months

• Motor Function

  rate of torque development

  3 months

Secondary Outcomes (5)

• Systemic oxidative stress and inflammation

  3 months

• Number of participants with additional measures of motor ability

  3 months

• endothelial cell oxidative stress and inflammation

  3 months

• plasma metabolites

  3 months

• NIH Toolbox cognition test battery

  3 months

Other Outcomes (1)

• neural activation

  3 months

Study Arms (2)

Sodium Nitrite Supplementation

EXPERIMENTAL

80 mg/day (40 mg 2x/day) slow release sodium nitrite (TheraVasc, Inc) for 3 months

Drug: Sodium nitrite

Placebo

PLACEBO COMPARATOR

placebo 2x/day for 3 months

Drug: Placebo

Interventions

Sodium nitrite DRUG

Sodium Nitrite Supplementation

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 60 Years - 79 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 60-79 years. Women will be confirmed as postmenopausal (either natural or surgical) based on cessation of menses for \>1 year.
• Ability to provide informed consent
• Score \>22 on the mini mental state exam (MMSE) to allow a broad range of normal and mildly-impaired cognitive abilities, but function adequate to understand and complete trials (214)
• Blood pressure (BP) \>100/60 mmHg for past 3 mo (rationale: blood pressure below 100/60 mmHg may elevate the normally small risk of hypotension with sodium nitrite treatment)
• Ability to perform motor and cognitive tests (e.g., can rise from a chair, walk for 2 min, climb 10 stairs)
• Willing to accept random assignment to condition (older adults)

You may not qualify if:

• High dietary nitrate intake or current nitrite supplementation; hypersensitivity to nitrates or nitrites
• Glucose-6-phosphate dehydrogenase deficiency or blood methemoglobin \>2%
• Current smoking
• Having past or present alcohol dependence or abuse, as defined by the American Psychiatry Association, Diagnostic and Statistical Manual of Mental Disorders
• Body mass index (BMI) \>40 kg/m2 (FMD measurements can be inaccurate in severely obese patients)
• Chronic clinical diseases (e.g., coronary artery/peripheral artery/cerebrovascular diseases, diabetes, chronic kidney disease requiring dialysis, neurological disorders or diseases that may affect motor/cognitive functions \[multiple sclerosis, Parkinson's disease, polio, Alzheimer's disease, dementia or other brain diseases of aging\]), except hypertension and hyperlipidemia.
• Regular vigorous aerobic/endurance exercise (\>3 vigorous bouts/week)
• Not weight stable in the prior 3 months (\>2 kg weight change) or unwilling to remain weight stable throughout study (rationale: recent weight change or weight loss can influence vascular function and small metabolite signature(216))
• Current treatment or recent cessation (\< 3 mo) of hormone replacement therapy.
• Moderate or severe peripheral artery disease (ankle-brachial index \<0.7)(183)
• A graded exercise test will be performed by all subjects, if there is physician concern or an adverse event, the subject will not participate in a maximal oxygen consumption test (this will be determined in accordance with stated contraindications for exercise testing provided by the American Heart Association)(217)
• Claustrophobia, metal implants, etc., affecting feasibility and/or safety of the fMRI scanning.

Sponsors & Collaborators

• University of Colorado, Boulder: lead

Study Sites (1)

Clinical Translational Research Center

Boulder, Colorado, 80309, United States

Location

Related Publications (2)

• Rossman MJ, Gioscia-Ryan RA, Santos-Parker JR, Ziemba BP, Lubieniecki KL, Johnson LC, Poliektov NE, Bispham NZ, Woodward KA, Nagy EE, Bryan NS, Reisz JA, D'Alessandro A, Chonchol M, Sindler AL, Seals DR. Inorganic Nitrite Supplementation Improves Endothelial Function With Aging: Translational Evidence for Suppression of Mitochondria-Derived Oxidative Stress. Hypertension. 2021 Apr;77(4):1212-1222. doi: 10.1161/HYPERTENSIONAHA.120.16175. Epub 2021 Mar 1.

  PMID: 33641356 DERIVED

• Jones AM, Vanhatalo A, Seals DR, Rossman MJ, Piknova B, Jonvik KL. Dietary Nitrate and Nitric Oxide Metabolism: Mouth, Circulation, Skeletal Muscle, and Exercise Performance. Med Sci Sports Exerc. 2021 Feb 1;53(2):280-294. doi: 10.1249/MSS.0000000000002470.

  PMID: 32735111 DERIVED

Related Links

• description of our laboratory

MeSH Terms

Interventions

Sodium Nitrite

Intervention Hierarchy (Ancestors)

Nitrites; Nitrous Acid; Nitrogen Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Matthew J Rossman, PhD

  University of Colorado, Boulder

  STUDY DIRECTOR

• Douglas R Seals, PhD

  University of Colorado, Boulder

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 13, 2015
• First Posted: March 19, 2015
• Study Start: March 1, 2015
• Primary Completion: May 1, 2019
• Study Completion: May 1, 2019
• Last Updated: December 5, 2019

Record last verified: 2019-12

Locations

US (1)