Red Blood Cell ATP Release and Vascular Function in Humans

Cardiovascular Diseases Clinical Trial

Official title:

Red Blood Cell ATP Release and Vascular Function in Humans

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03404843
• Other study ID #: 16-6361H
• Status: Completed
• Phase: Phase 2
• Start date: July 14, 2017
• Est. completion date: October 5, 2018

Study information

• Verified date: February 2020
• Source: Colorado State University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Previous work demonstrates that the red blood cells of older adults do not release a potent vasodilator (ATP) as well as the red blood cells of younger adults. The investigators are targeting a pathway within the red blood cell using fasudil hydrochloride to determine if both the release of ATP from red blood cells and blood flow responses to low oxygen (hypoxia) and exercise in older adults can be improved.

Description:

Participants will initiate contact with the investigators by responding to flyers placed in the community either by phone or email. The first correspondence (phone or email) will provide a brief description of the research and ask a series of screening questions to determine age, height, weight, and any medications participants may be taking as well as the current health status (diagnoses, basic health history, and physical activity level) of participants. If they qualify, a two hour screening visit is scheduled during a time when the participant will be examined by the physician. All participants will undergo informed consent in a face to face private meeting with the research coordinator. Following informed consent, participants will be evaluated by a physician and undergo a treadmill stress test to rule out cardiovascular disease.

During the study, heart rate will be monitored with a 3-lead ECG and blood pressure will be monitored noninvasively with a blood pressure cuff on the finger (finometry). Venous blood will be collected at multiple time points via a catheter inserted into a forearm vein draining skeletal muscle circulation for measurement of blood gases (0.5 mL/sample) and plasma [ATP] (2 mL/sample), with less than 100 mL of blood being drawn in total (~60mL total). Blood flow at rest and in response to hypoxia and exercise will be measured non-invasively using Doppler ultrasound of the brachial artery. Hypoxia trials will be performed by having participants breathe a low oxygen gas mixture via a mouthpiece that is hooked up to gas tanks and an anesthesia monitor to decrease their oxygen saturation to ~80% (similar to hiking a 14er) for 10 minutes. Exercise trials will last for approximately 15 minutes and will involve participants performing graded-intensity rhythmic handgrip exercise by lifting weights (corresponding to a low, moderate, and high workload) using a pulley system. The drug treatment used in this study (fasudil) is being given because it may improve red blood cell ATP release in older adults. This is a double-blinded placebo controlled study, thus participation will occur on two randomized experimental days.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: October 5, 2018
• Est. primary completion date: October 5, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Healthy

• Sedentary to moderately active

• 18 to 30 years old for young subjects

• 60 to 80 years old for older subjects

Exclusion Criteria:

• Obesity (BMI = 30 kg/m^2)

• Cardiovascular disease

• Metabolic disease

• Use of medications that can influence cardiovascular function

• Blood pressure greater than or equal to 140/90

• Smoker

• Use of hormone replacement therapy

Related Conditions & MeSH terms

• Cardiovascular Diseases

Intervention

Drug:
• Fasudil Hydrochloride
10 mg/mL vial of fasudil hydrochloride. 6 mL (60 mg) of fasudil hydrochloride are added to a 100 mL saline bag for delivery to subjects.

Other:
• Saline
100 mL saline bag.

Locations

Country	Name	City	State
United States	Colorado State University, Dept. of Health and Exercise Science	Fort Collins	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
Colorado State University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Forearm Blood Flow Responses to Hypoxia After Administration of Intervention	Forearm blood flow measured using Doppler ultrasound before and after 5 minutes of exposure to hypoxia (breathing a mix of low-oxygen gas and room air to achieve oxygen saturations of ~80%).	Within 4 hours after administration of intervention
Primary	Forearm Blood Flow Responses to Exercise After Administration of Intervention	Forearm blood flow measured using Doppler ultrasound before and during continuous rhythmic handgrip exercise at a low, moderate, and high intensity workload (4 minutes at each workload for 12 minutes in total).	Within 4 hours after administration of intervention
Primary	Change in ATP Release to Hypoxia After Administration of Intervention	Venous plasma concentrations of ATP measured using a luminometer before and after 5 minutes of exposure to hypoxia (breathing a mix of low-oxygen gas and room air to achieve oxygen saturations of ~80%).	Within 4 hours after administration of intervention
Primary	Change in ATP Release to Exercise After Administration of Intervention	Venous plasma concentrations of ATP measured using a luminometer before and during continuous rhythmic handgrip exercise at a low, moderate, and high intensity workload (4 minutes at each workload for 12 minutes in total).	Within 4 hours after administration of intervention
Secondary	Arterial Stiffness After Administration of Intervention	Arterial stiffness measured non-invasively using a SphygmoCor system after administration of saline (placebo) and fasudil. This is a randomized crossover design study, so participants will receive 1 treatment (saline or fasudil) on their first visit and the other treatment on their second visit.	Immediately following administration of intervention

External Links

•   Lab website