Clinical trial NCT05227781: 8 Weeks of L-CIT Supplementation and LIRET on Vascular Function in Hypertensive Postmenopausal Women
Official title: 8 Weeks of L-Citrulline Supplementation to Improve Low-intensity Resistance Exercise Training Vascular Adaptations in Postmenopausal Women With Hypertension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hypertension
Menopause
Keywords: Endothelial Function
Arterial Stiffness
Muscle Function
Lead sponsor: Texas Tech University
Sponsor class: OTHER
First posted: 2022-02-07
Enrollment: 29
Sex: FEMALE
Minimum age (years): 50
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-blind (subject, investigator), randomized, parallel, placebo-controlled
Primary purpose: BASIC_SCIENCE

Brief summary: The overall objective of this project is to bring forth evidence that L-Citrulline (L-CIT) supplementation and low intensity resistance exercise training (LIRET) alone and combined will improve vascular function and muscle fitness (mass, strength, and exercise performance) in postmenopausal women with hypertension. The investigators' central hypothesis is that adjuvant L-CIT supplementation may synergistically enhance vascular (arterial stiffness, BP, muscle oxygenation, blood flow) and muscular (strength, exercise performance) responses to LIRET in postmenopausal women with hypertension by improving endothelial vasodilatory function.

Detailed description: Individuals who are on medications will refrain from use the morning of all laboratory visits. Participants will be asked to bring medications with them, and will be allowed to ingest it after the vascular measurements have been obtained.

There will be a total of 7 laboratory visits. The 1st visit will be approximately 1 hr and 45 minutes. The 2nd and 3rd visit will be approximately 2 hrs. The 4th and 6th visit will total about 2 hrs and 15 minutes and finally, the 5th and 7th visit will total about 1hr and 15 minutes. This means the total participant time for laboratory visits will be approximately 12 hours. In addition to this, the second 4 weeks of the 8 week study period will involve coming to the Kinesiology and Sport Management building at Texas Tech University main campus 3 times per week to perform the low-intensity resistance training intervention. These visits should last no more than 30-45 minutes.

The first 3 visits will be separated by 48-72 hrs. Visits 3 and 4 will be separated by 4 weeks (first 4 weeks of LCIT or Placebo supplementation). Visits 4 and 5 will be separated by 48-72 hours. Visits 5 and 6 will again be separated by 4 weeks (Second 4 weeks of LCIT or Placebo supplementation with the addition of Low-intensity resistance exercise in both groups).

Approximately 12 hours total for each of the 7 laboratory visits, as well as 30-45 minutes 3 times per week during the last 4 weeks of the 8 week study.

Using a parallel placebo-controlled design, postmenopausal women with elevated blood pressure or hypertension will be randomized to receive L-CIT supplementation (10g/day) alone for 4 weeks, followed by 4 weeks of L-CIT supplementation in combination with low-intensity resistance training or placebo (maltodextrin) alone for 4 weeks, followed by 4 weeks of placebo in combination with low-intensity resistance training.

Differences between conditions (Citrulline vs Placebo) will be analyzed with independent samples t-test. Two-way ANOVA with repeated measures with Bonferroni adjustments will be used to analyze group (CIT vs. PL) by time (baseline, post-supplementation only, supplement + low-intensity resistance exercise training) interactions between the outcome variables. If group-by-time interactions are detected, post-hoc comparisons will be performed via paired or independent t-tests.

Eligibility criteria: Inclusion Criteria:

* Women aged 50-75 years
* Resting systolic BP 120-159 mmHg
* Sedentary (\< 60 min of exercise/week)
* Body mass index of 18.5-39.9 kg/m2)
* Fasting glucose \< 126 mg/dL
* HbA1c \< 6.4%.

Exclusion Criteria:

* Body mass index ≥ 40 or \< 18.5 kg/m2
* Diagnosed with type 1 or 2 diabetes mellitus
* Cardiovascular diseases
* Systolic blood pressure \> 170 mmHg or on more than two anti-hypertensive medication
* Other chronic diseases such as cancer, asthma, glaucoma, thyroid, kidney, liver and pancreatic disease
* Individuals incorporated in a weight loss program and aerobic or resistance training program
* Heavy smokers (\> 20 cigarettes per day)
* Heavy drinkers (\> 12 alcoholic drinks per week)

Primary outcomes:
measure: Changes in endothelial function via brachial artery flow-mediated dilation (effects of L-Citrulline only)
timeFrame: 4 weeks
measure: Changes in endothelial function via superficial femoral artery flow-mediated dilation (effects of L-Citrulline only)
timeFrame: 4 weeks
measure: Changes in endothelial function via brachial artery flow-mediated dilation (effects of L-Citrulline combined with low-intensity resistance exercise training)
timeFrame: 4 weeks
measure: Changes in endothelial function via superficial femoral artery flow-mediated dilation (effects of L-Citrulline combined with low-intensity resistance exercise training)
timeFrame: 4 weeks
measure: Changes in arm exercise blood flow (effects of L-Citrulline only)
timeFrame: 4 weeks
measure: Changes in leg exercise blood flow (effects of L-Citrulline only)
timeFrame: 4 weeks
measure: Changes in arm exercise blood flow (effects of L-Citrulline combined with low-intensity resistance exercise training)
timeFrame: 4 weeks
measure: Changes in leg exercise blood flow (effects of L-Citrulline combined with low-intensity resistance exercise training)
timeFrame: 4 weeks
Secondary outcomes:
measure: Changes in arterial stiffness via arm, leg, and aortic pulse wave velocity (effects of L-Citrulline only)
timeFrame: 4 weeks
measure: Changes in arterial stiffness via arm, leg, and aortic pulse wave velocity (effects of L-Citrulline combined with low-intensity resistance exercise training)
timeFrame: 4 weeks
measure: Changes in aortic hemodynamics using pulse wave analysis (effects of L-Citrulline only)
timeFrame: 4 weeks
measure: Changes in aortic hemodynamics using pulse wave analysis (effects of L-Citrulline combined with low-intensity resistance exercise training)
timeFrame: 4 weeks
measure: Changes in brachial and aortic blood pressure via automated sphygmomanometry (effects of L-Citrulline only)
timeFrame: 4 weeks
measure: Changes in brachial and aortic blood pressure via automated sphygmomanometry (effects of L-Citrulline combined with low-intensity resistance exercise training)
timeFrame: 4 weeks
measure: Changes in muscle strength (effects of L-Citrulline only)
timeFrame: 4 weeks
measure: Changes in muscle strength (effects of L-Citrulline combined with low-intensity resistance exercise training)
timeFrame: 4 weeks
measure: Quantification of L-Arginine (effects of L-Citrulline only)
timeFrame: 4 weeks
measure: Quantification of Arginase (effects of L-Citrulline only)
timeFrame: 4 weeks
measure: Quantification of nitric oxide (effects of L-Citrulline only)
timeFrame: 4 weeks
measure: Quantification of Endothelin-1 (effects of L-Citrulline only)
timeFrame: 4 weeks
measure: Quantification of L-Ornithine (effects of L-Citrulline only)
timeFrame: 4 weeks
measure: Quantification of L-Arginine (effects of L-Citrulline combined with low-intensity resistance exercise training)
timeFrame: 4 weeks
measure: Quantification of arginase (effects of L-Citrulline combined with low-intensity resistance exercise training)
timeFrame: 4 weeks
measure: Quantification of nitric oxide (effects of L-Citrulline combined with low-intensity resistance exercise training)
timeFrame: 4 weeks
measure: Quantification of endothelin-1 (effects of L-Citrulline combined with low-intensity resistance exercise training)
timeFrame: 4 weeks
measure: Quantification of L-Ornithine (effects of L-Citrulline combined with low-intensity resistance exercise training)
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Lubbock
country: United States
facility: Texas Tech University
state: Texas
Study officials:
affiliation: Texas Tech University
name: Arturo Figueroa
role: PRINCIPAL_INVESTIGATOR
References: