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Effect of Oral Caffeine and L-Citrulline Supplementation on Arterial Function in Healthy Males

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02214290
Recruitment Status : Completed
First Posted : August 12, 2014
Results First Posted : December 29, 2020
Last Update Posted : December 29, 2020
Sponsor:
Information provided by (Responsible Party):
Arturo Figueroa, Florida State University

Tracking Information
First Submitted Date  ICMJE August 4, 2014
First Posted Date  ICMJE August 12, 2014
Results First Submitted Date  ICMJE November 30, 2018
Results First Posted Date  ICMJE December 29, 2020
Last Update Posted Date December 29, 2020
Study Start Date  ICMJE September 2012
Actual Primary Completion Date March 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 2, 2020)
Aortic Blood Pressure [ Time Frame: Baseline and Day 7 (Calculated change between rest and 30 minutes post-caffeine ingestion at these time points) ]
Aortic blood pressure at rest and 30 minutes after acute ingestion of 200 mg of caffeine before and after 7 days of either 6g/day of Citrulline or 6 g/day of Placebo.
Original Primary Outcome Measures  ICMJE
 (submitted: August 8, 2014)
Blood Pressures [ Time Frame: One week ]
Measuring brachial, ankle, and central blood pressures acutely following caffeine tablet versus placebo and following L-citrulline supplementation.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 2, 2020)
  • Changes in Reflected Wave Pressure (P2) [ Time Frame: Baseline and Day 7 (Calculated change between rest and 30 minutes post-caffeine ingestion at these time points) ]
    Reflected wave pressure at rest and 30 minutes after ingestion of 200mg of caffeine after 7 days supplementation of 6g/day of either L-Citrulline or Placebo.
  • Changes in Femoral-ankle Pulse Wave Velocity After 7 Days of Either L-Citrulline or Placebo (6g/Day) [ Time Frame: Baseline and Day 7 (Calculated change between rest and 30 minutes post-caffeine ingestion at these time points) ]
    Femoral-ankle pulse wave velocity at rest and 30 minutes after ingestion of 200mg of caffeine after 7 days supplementation of 6g/day of either L-Citrulline or Placebo.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 8, 2014)
Arterial Function [ Time Frame: One week ]
Measuring arterial stiffness (PWV) and wave reflection at rest, acutely after caffeine or placebo, and following L-citrulline supplementation.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effect of Oral Caffeine and L-Citrulline Supplementation on Arterial Function in Healthy Males
Official Title  ICMJE Effect of Oral Caffeine and L-Citrulline Supplementation on Arterial Function in Healthy Males
Brief Summary Caffeine is an exceedingly popular and consumed pharmacological agent. Although caffeine is primarily consumed from coffee and tea beverages, it is also available in other forms such as sodas, energy drinks, tablets and capsules. Nevertheless, caffeine acutely increases brachial and aortic systolic blood pressure (BP) and arterial stiffness. Arterial stiffness is an independent predictor of cardiovascular disease (CVD) and assessed through pulse wave velocity (PWV). Interestingly, previous studies have proposed that caffeine may increase aortic BP through increases in aortic PWV and augmentation index (AIx), a measurement of wave reflection. Yet, these effects were seen in middle-aged adults with treated hypertension and a wide age range. Therefore, it is imperative to consider that caffeine may cause different effects in young normotensive individuals than in older adults independently of BP levels. Importantly, oral supplementation of the amino-acid, L-citrulline has been shown to enhance the bioavailability of L-arginine levels and nitric oxide (NO) production and, therefore, improve arterial function. L-citrulline supplementation for 7 days given at 6 g/day has shown to increase NO levels while improving PWV. Previous studies by our group also demonstrated that L-citrulline supplementation reduces the BP response to cold exposure; a condition with an increased vasoconstriction. Therefore, the acute effects of caffeine on central and peripheral PWV and BP in healthy young men are yet to be fully evaluated. We hypothesized that acute caffeine intake would increase peripheral and aortic BP and PWV and that L-citrulline supplementation would attenuate the effects induced by acute caffeine ingestion.
Detailed Description

The specific aims of this study are:

AIM 1: To examine the effects of the acute ingestion of 200mg caffeine (tablets) on arterial function in young adults. The working hypothesis is that acute caffeine intake would increase brachial, ankle and aortic BP, PWV (aortic and leg), and wave reflection. In order to test this hypothesis, the investigators will perform non-invasive measurements of arterial stiffness (aortic and leg PWV) and pulse wave analysis (aortic BP and AIx) using applanation tonometry of the radial artery 30, 45, and 60 minutes following caffeine ingestion.

AIM 2: To determine the effectiveness of L-citrulline supplementation to attenuate the acute cardiovascular effects of caffeine ingestion. The working hypothesis is that 7 days of L-citrulline supplementation will attenuate the unfavorable arterial responses (increases in BP, PWV, and wave reflection) to acute caffeine ingestion. In order to test this hypothesis, the investigators will perform the same procedures previously specified in AIM 1.

Description of the study:

Sixteen healthy young men 18-40 years of age will be enrolled in this study. Participants with CVD history, resting BP (> 160/100 mmHg), recent history of smoking, or considered competitive athlete will be excluded from the study. All subjects will refrain from food and caffeine for > 8 hours and from exercise for > 24 hours before testing.

Study design:

Following an initial screening, arterial function measurements will be collected. Measurements will be assessed at baseline following 10 minutes of rest in the supine position and then again at 30, 45, and 60 minutes after 200 mg caffeine or placebo ingestion. Participants will receive caffeine or placebo supplementation on two separate visits with a minimum of 48 hours in between sessions. Following the acute phase of the study, subjects will be randomized to consume L-citrulline or placebo for 7 days given at 6 grams/day. Following the same protocol as the acute phase with 200 mg caffeine, measurements will be collected before and after the 7 day supplementation period.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Other
Condition  ICMJE
  • Hypertension
  • Healthy
Intervention  ICMJE
  • Drug: Caffeine
    A 200 mg caffeine tablet was given to subject to examine the drugs effect on arterial function.
    Other Name: Caffeine tablet (CVS Pharmacy)
  • Drug: Placebo
    A 750 mg placebo capsule (maltodextrin) was given to subjects to examine the effect of the drug on arterial function.
    Other Name: Placebo from NOW FOODS, USA
  • Dietary Supplement: L-citrulline
    L-citrulline was used to examine the effect of the supplement on arterial function.
    Other Name: L-citrulline (750 mg/capsule)
Study Arms  ICMJE
  • Active Comparator: Caffeine
    200 mg caffeine tablet produced by CVS Pharmacy, USA
    Intervention: Drug: Caffeine
  • Placebo Comparator: Placebo
    Placebo pill produced by NOW FOODS, USA
    Intervention: Drug: Placebo
  • Experimental: L-citrulline
    L-citrulline capsule (750 mg) provided by NOW FOODS
    Intervention: Dietary Supplement: L-citrulline
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 8, 2014)
16
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE March 2014
Actual Primary Completion Date March 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Young healthy males
  • Non smoker
  • Non endurance trained athlete
  • No previous history of cardiovascular disease

Exclusion Criteria:

  • Female
  • Blood pressure greater than 160/100
  • Smoker
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years to 40 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02214290
Other Study ID Numbers  ICMJE HSC2013.10514
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Arturo Figueroa, Florida State University
Study Sponsor  ICMJE Florida State University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Arturo Figueroa, M.D. Ph.D Florida State University
PRS Account Florida State University
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP