Nitrate Supplementation and Cerebrovascular and Cognitive Function in Metabolic Syndrome

NCT05532423 | Completed Early Phase 1 FDA Drug

• 1 other identifier: STUDY00020830
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine if beetroot juice consumption can improve cognitive performance and brain vascular function in individuals with metabolic syndrome

Conditions

Metabolic Syndrome

Keywords

Cognition

Outcome Measures

Primary Outcomes (4)

• Cognitive Functioning - Change in N-back test performance

  Reaction time of responses for each trial type (0-back, 1-back, 2-back, and 3-back)

  At Baseline, 90 minutes following drinking the beetroot juice (single 140mL acute dose), 90 minutes following drinking the placebo drink (single 140mL acute dose), and after 4 weeks of daily (70mL) beetroot juice consumption

• Cognitive Functioning - Change in N-back test performance

  Percent accuracy of correct responses for each trial type (0-back, 1-back, 2-back, and 3-back)

  At Baseline, 90 minutes following drinking the beetroot juice (single 140mL acute dose), 90 minutes following drinking the placebo drink (single 140mL acute dose), and after 4 weeks of daily (70mL) beetroot juice consumption

• Changes in Cerebral Autoregulation - NIRx (fNIRS/cerebral oxygenation) and finapres (blood pressure) derived waveforms for transfer function analysis

  This outcome will be measured using non-invasive methodology utilizing fNIRS and will involve rhythmic breathing to determine the relation between blood pressure and an index of blood flow. The variable of interest is the phase derived from transfer function analysis of the blood pressure and fNIRS waveforms.

  At Baseline, 90 minutes following drinking the beetroot juice (single 140mL acute dose), 90 minutes following drinking the placebo drink (single 140mL acute dose), and after 4 weeks of daily (70mL) beetroot juice consumption

• Changes in Neurovascular Coupling - changes in fNIRS signals during the N-back cognitive test

  This outcome will also be measured using fNIRS and will involve measurement of brain oxygenation during cognitive assessment. The variable of interest will be changes in fNIRS oxyhemoglobin and deoxyhemoglobin signals (% change from baseline) during the cognitive assessment (n-back test).

  At Baseline, 90 minutes following drinking the beetroot juice (single 140mL acute dose), 90 minutes following drinking the placebo drink (single 140mL acute dose), and after 4 weeks of daily (70mL) beetroot juice consumption

Secondary Outcomes (2)

• Changes in Pulse Wave Velocity - Colin Cardiovascular Profiling System 2000

  At Baseline, 90 minutes following drinking the beetroot juice (single 140mL acute dose), 90 minutes following drinking the placebo drink (single 140mL acute dose), and after 4 weeks of daily (70mL) beetroot juice consumption

• Taste Profile of Juice (Sweetness, Bitterness, and Sourness) - Questionnaire developed in our lab

  This will be taken one time, at the last study visit after 4 weeks of juice consumption

Study Arms (2)

Metabolic Syndrome Older Adult

EXPERIMENTAL

Participants with metabolic syndrome will be drinking nitrate rich beetroot juice from the James White Beet It company. Participants will drink one dose of 140mL beetroot juice for two visits of either a nitrate rich juice or a nitrate depleted placebo drink. Both drinks taste and smell the same, just with the active component removed. Following these visits, participants will drink 70ml of nitrate rich beetroot juice daily for 4 weeks to investigate long term effects of the juice on study outcomes.

Drug: Beetroot Juice - Active

Metabolic Syndrome Older Adult - Placebo juice condition

EXPERIMENTAL

Participants with metabolic syndrome will be drinking nitrate rich beetroot juice from the James White Beet It company. Participants will drink one dose of 140mL beetroot juice for two visits of either a nitrate rich juice or a nitrate depleted placebo drink. Both drinks taste and smell the same, just with the active component removed. Following these visits, participants will drink 70ml of nitrate rich beetroot juice daily for 4 weeks to investigate long term effects of the juice on study outcomes.

Drug: beetroot juice - Placebo

Interventions

Beetroot Juice - Active DRUG

Participants with Metabolic syndrome will drink 140mL of organic nitrate rich beetroot juice from the James White Beet It Company. This juice will be the active juice, meaning it has the high nitrate content that is of interest. This drink will be given two 70 mL bottles of the juice that will be blinded to them and investigators.

Also known as: Experimental

Metabolic Syndrome Older Adult

beetroot juice - Placebo DRUG

Participants with Metabolic syndrome will drink 140mL of organic nitrate rich beetroot juice from the James White Beet It Company. This drink will be the placebo drink, which means all of the nitrate has been extracted, however it tastes and smells the same as the active drink. This drink will be given two 70 mL bottles of the juice that will be blinded to them and investigators.

Also known as: Placebo

Metabolic Syndrome Older Adult - Placebo juice condition

Eligibility Criteria

• Age: 55 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• MetS classification according to NCEP III definition - MetS group only … at least 3 of the 5 components Individuals with a waist circumference \>102 cm (40 in) for men \> 88 cm for women Triglycerides ≥150 mg/dL HDL cholesterol ≤ 50 mg/dL for women and ≤ 40 mg/dL for men Blood pressure ≥130/85 mmHg Fasting blood glucose ≥100 mg/dL Age 55-75 Men and women All races and ethnicities

You may not qualify if:

• Individuals with any overt cardiovascular, hematologic, pulmonary, renal, musculoskeletal, and/or neurological disease(s).
• Premenopausal women - indicated by mention of last menstrual cycle
• Individuals with active cancer
• Individuals with moderate/severe depressive disorder as indicated by BDI-II scores (BDI-II score \>14)
• Individuals with cognitive impairment as indicated by the MMSE (score on the MMSE \< 24)
• Individuals with visual impairment
• Users of any tobacco and/or nicotine products (smokers, chewing tobacco, nicotine-containing patches/gum, smokeless cigarettes)
• Individuals taking hormone replacement
• Taking following an of the following medications:
• nitrates (e.g. nitroglycerin) for angina
• phosphodiesterase inhibitors (e.g., Viagra)
• anti-Inflammatory drugs

Sponsors & Collaborators

• Penn State University: lead

Study Sites (1)

Penn State University, Noll Lab

University Park, Pennsylvania, 16802, United States

Location

MeSH Terms

Conditions

Metabolic Syndrome

Condition Hierarchy (Ancestors)

Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: As it is a double blind study, participants and investigators for this study will be blinded to the intervention they are receiving.
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: The design is a single group randomized crossover trial, with individuals with metabolic syndrome receiving both the active nitrate rich juice and the placebo juice, randomized in order.

Study Record Dates

• First Submitted: August 26, 2022
• First Posted: September 8, 2022
• Study Start: December 1, 2022
• Primary Completion: August 1, 2024
• Study Completion: August 1, 2024
• Last Updated: May 6, 2025

Record last verified: 2025-05

Locations

US (1)