Clinical trial NCT02393742: Nitrite Supplementation for Improving Physiological Function in Older Adults
Official title: Efficacy of Oral Sodium Nitrite for Improving Physiological Functions in Older Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Ageing
Lead sponsor: University of Colorado, Boulder
Sponsor class: OTHER
First posted: 2015-03-19
Enrollment: 49
Sex: FEMALE
Minimum age (years): 60
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.


Eligibility criteria: Inclusion Criteria:

* • 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)
  * Baseline brachial flow-mediated dilation (FMD) \< 7%Δ (rationale: non-invasive screening to ensure exclusion of subjects with exceptionally high baseline endothelial function(215))
  * 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)

Exclusion Criteria:

* • 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.

Primary outcomes:
measure: Vascular Function
timeFrame: 3 months
measure: Motor Function
timeFrame: 3 months
Secondary outcomes:
measure: Systemic oxidative stress and inflammation
timeFrame: 3 months
measure: Number of participants with additional measures of motor ability
timeFrame: 3 months
measure: endothelial cell oxidative stress and inflammation
timeFrame: 3 months
measure: plasma metabolites
timeFrame: 3 months
measure: NIH Toolbox cognition test battery
timeFrame: 3 months
Other outcomes:
measure: neural activation
timeFrame: 3 months
Locations:
city: Boulder
country: United States
facility: Clinical Translational Research Center
state: Colorado
Study officials:
affiliation: University of Colorado, Boulder
name: Matthew J Rossman, PhD
role: STUDY_DIRECTOR
affiliation: University of Colorado, Boulder
name: Douglas R Seals, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.