Creatine Monohydrate Supplementation and Vascular Endothelial Health

NCT05014659 | Completed

• 1 other identifier: STUDY00000764
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

To determine the effects of 4 weeks of creatine monohydrate supplementation on markers of macrovascular and microvascular function, cognitive performance, and physical performance.

Conditions

Endothelial Dysfunction; Oxidative Stress

Keywords

Older adults; Flow mediated dilation

Outcome Measures

Primary Outcomes (11)

• Change from baseline in brachial artery flow mediated dilation (FMD%) at week 4

  FMD% is a validated, non-invasive, standardized method of measuring the ability of an artery to respond to a stimulated increase in blood flow via vasodilation. Increase in blood flow will be stimulated by inflating a forearm cuff for 5 minutes, then rapidly releasing this cuff. Brachial artery in the participants right arm will be identified/imaged using a Philips Doppler Ultrasound. Resting diameter will be measured in millimeters, and max dilation will be the maximum diameter in millimeters following increased blood flow (cuff release). FMD% will be calculated by \[(max diameter - resting diameter) / resting diameter\] x 100. Change = Week 4 Score - Baseline Score

  Baseline and Week 4

• Change from baseline in forearm microvascular reperfusion rate (%/sec) at week 4

  Microvascular reperfusion rate will be assessed using a near-infrared spectroscopy (NIRS) unit placed on the forearm during the FMD assessment. This small, non-invasive NIRS unit will allow for the determination of forearm muscle tissue oxygen saturation during FMD. The microvascular reperfusion rate (%/sec) will be determined by analyzing the upward slope of tissue saturation following FMD cuff release. Change = Week 4 Score - Baseline Score

  Baseline and Week 4

• Change from baseline in brachial-ankle pulse wave velocity (baPWV) at week 4

  PWV is a validated, non-invasive, clinical technique used to measure arterial stiffness. Participants will lay supine, and 4 blood pressure cuffs will be wrapped around the limbs. One cuff on each arm (brachial artery) and one cuff on each ankle (posterior tibial artery). The distance between the two sampling points (arms and ankles) will be calculated according to the height of the subject. PWV is measured as the distance between two recording sites divided by the transit time of the pulse wave detected. PWV will be given as meters/second. Change = Week 4 Score - Baseline Score

  Baseline and Week 4

• Change from baseline in augmentation (AUG) and augmentation index (AIx) using pulse wave analysis (PWA) at week 4

  Both AUG and AIx are determined based on waveforms captured using a pulse wave analysis device (PWA). PWA is a validated, non-invasive technique used to determine central arterial stiffness via the assessment of the radial pulse (wrist). PWA will be measured using a tonometer which is gently pressed against the radial pulse point. Ten seconds of high-quality waveforms will be captured and analyzed to determine AUG (the pressure added to the forward wave by the reflected wave; measured in mmHg) and AIx (a measure of the effect of the wave reflection on the second systolic peak; expressed as a %). Change = Week 4 Score - Baseline Score

  Baseline and Week 4

• Change from baseline in oxidized low density lipoprotein (oxLDL) at week 4

  OxLDL is a commonly used, validated, blood biomarker of lipid oxidation. OxLDL is thereby indicative of oxidative stress. A small amount of venous blood will be drawn (\~5ml) at the beginning of every visit, centrifuged, and then stored in a -80 freezer. Plasma will later be used to analyze levels of OxLDL using a commercially available enzyme-linked immunoassay. Change = Week 4 Score - Baseline Score

  Baseline and Week 4

• Change from baseline in tetrahydrobiopterin (BH4) at week 4

  BH4 is a very important cofactor necessary for the natural production of nitric oxide - a substance produced by the body and majorly responsible for the vasodilation (increase in diameter) of major arteries, such as the brachial artery. BH4 has been shown to decrease with age and with higher levels of systemic oxidative stress. A small amount of venous blood will be drawn (\~5ml) at the beginning of every visit, centrifuged, and then stored in a -80 freezer. Plasma will then later be used to analyze levels of BH4 using a commercially available enzyme-linked immunoassay. Change = Week 4 Score - Baseline Score

  Baseline and Week 4

• Change from baseline in malondialdehyde (MDA) at week 4

  MDA is a commonly used, validated, blood biomarker of oxidative stress. A small amount of venous blood will be drawn (\~5ml) at the beginning of every visit, centrifuged, and then stored in a -80 freezer. Plasma will then later be used to analyze levels of MDA using a commercially available enzyme-linked immunoassay. Change = Week 4 Score - Baseline Score

  Baseline and Week 4

• Change from baseline in total 6-minute walking distance (6MWT) at week 4

  The 6 minute walk test (6MWT) assesses distance walked over 6 minutes as a sub-maximal test of aerobic capacity/endurance. The participant will be asked to walk on a pre-measured track for a total of 6 minutes, and total distance covered will be measured in meters following completion. Change = Week 4 Score - Baseline Score

  Baseline and Week 4

• Change from baseline in total torque produced (total Nm) per set at week 4

  In order to assess physical performance, participants will perform right knee extension and flexion for a total of 3 sets, each consisting of 30 repetitions, with 1 minute recovery between each set. This assessment will be carried out on a Biodex Isokinetic Dynamometer, which will track force produced in Newton meters (Nm) for each repetition. For each individual set, the peak torque of each repetition will be summed, and this value will be used to represent isokinetic performance. This data will be presented as total newton-meters (Nm) produced per set. Change = Week 4 Set 1 Score - Baseline Set 1 Score Week 4 Set 2 Score - Baseline Set 2 Score Week 4 Set 3 Score - Baseline Set 3 Score

  Baseline and Week 4

• Change from baseline in time taken to complete (seconds) the Trail Making Test (TMT) at Week 4

  The TMT is a measurement of visual attention and task switching and has been validated for its use in neuropsychological assessment. Both parts of the TMT (Part A + Part B) consist of 25 circles distributed over a sheet of white paper. In Part A of the TMT, circles are numbered 1 - 25, and the participant will be instructed to connect numbers consecutively in ascending order (ex. 1,2,3,4…). In Part B of the TMT, circles include both numbers (1 - 13) and letters (A - L). Participants will also be asked to draw lines to connect these circles in an ascending manner, but with the added task of alternating between numbers and letters (ex. 1-A-2-B-3-C…). During both trials the participant will be asked to connect the circles as quickly as possible. Time taken to complete each trial (Part A + Part B) will be recorded (seconds). Change = Week 4 Score - Baseline Score

  Baseline and Week 4

• Change from baseline in maximum number recall (#) achieved in the Digit Span memory recall test at Week 4

  A digit span (DS) memory recall test will be used to assess short-term memory. Both forward and backward DS testing remains one of the most widely utilized neuropsychological tests used to assess short-term verbal memory. Participants will complete both a forward-DS (FDS) and a backward-DS (BDS) test. Participants will be read a sequence of numbers at a rate of 1 digit/second, in a monotonous and clear tone. Each sequence will vary in length, from 2 numbers to 9 numbers. Participants will have 2 attempts to successfully repeat the sequence of numbers. The test will be discontinued after the failure to repeat a sequence on both attempts. Following this, participants will complete a BDS. Numbers will now have to be repeated backwards by the participant. Both digit span tests will be scored and reported separately as "span scores" (the maximum number of digits correctly produced forward or backwards by the participant). Change = Week 4 Score - Baseline Score

  Baseline and Week 4

Secondary Outcomes (6)

• Change from baseline in body fat percent (BF%) at week 4

  Baseline and Week 4

• Change from baseline in body lean mass (grams) at week 4

  Baseline and Week 4

• Change from baseline in body fat mass (grams) at week 4

  Baseline and Week 4

• Change from baseline in total body water (liters) at week 4

  Baseline and Week 4

• Change from baseline in resting systolic blood pressure (mmHg) at week 4

  Baseline and Week 4

Study Arms (2)

Creatine monohydrate

EXPERIMENTAL

Participants received 4 x 5g doses of creatine monohydrate (powdered form) for 5 days, followed by 1 x 5g doses of creatine monohydrate (powdered form) for 23 days.

Dietary Supplement: Creatine monohydrate

Placebo

PLACEBO COMPARATOR

Participants received 4 x 5g doses of placebo (powdered Maltodextrin) for 5 days, followed by 1 x 5g doses of placebo (powdered Maltodextrin) for 23 days.

Dietary Supplement: Placebo

Interventions

Creatine monohydrate DIETARY_SUPPLEMENT

4 x 5g doses daily for 5 days, followed by 1 x 5g dose daily for 23 days.

Creatine monohydrate

Placebo DIETARY_SUPPLEMENT

4 x 5g doses daily for 5 days, followed by 1 x 5g dose daily for 23 days.

Also known as: Maltodextrin

Placebo

Eligibility Criteria

• Age: 50 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• both male and female
• years old
• no restrictions based on race, ethnicity, or socioeconomic status
• sedentary individuals (\<20 minutes; \<3 days/wk. physical activity)
• post-menopausal women (has experienced 12 consecutive months without menstruation for \>5 years).

You may not qualify if:

• \<50 or ≥65 years of age
• Subjects participating in regular exercise (\>20 min/day, \>3 days/week)
• female subjects who are pregnant, lactating or 1 month post-partum
• currently consuming or had consumed creatine supplementation \<1 month prior to screening
• currently consuming or consumed nitric oxide supplementation \<1 month prior to screening
• currently consuming or had consumed Vitamin C supplementation \<2 weeks prior to screening
• individuals who report chronic infections
• individuals reporting paralysis due to stroke
• individuals reporting advanced Parkinson's disease
• individuals reporting severe rheumatoid arthritis or other serious orthopedic problems that would prevent performance of the exercise tasks
• individuals currently taking medications that may affect central or peripheral circulation
• individuals with known cardiovascular and/or metabolic disease
• current smokers or those who quit \<6 months prior to screening
• individuals with hypercholesterolemia (total cholesterol \> 200mg/dL, high density lipoprotein \<40 mg/dL, low density lipoprotein \>130mg/dL)
• individuals with hypertension (systolic blood pressure \> 150 mmHg and/or diastolic blood pressure \>95mmHg).

Sponsors & Collaborators

• Florida State University: lead

Study Sites (1)

Sandels Building

Tallahassee, Florida, 32306, United States

Location

MeSH Terms

Interventions

Creatine; maltodextrin

Intervention Hierarchy (Ancestors)

Guanidines; Amidines; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Holly E Clarke, PhD

  Florida State University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Study Record Dates

• First Submitted: August 19, 2021
• First Posted: August 20, 2021
• Study Start: October 17, 2020
• Primary Completion: December 12, 2022
• Study Completion: December 12, 2022
• Last Updated: January 13, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)