Red Blood Cell ATP Release and Vascular Function in Humans

NCT ID: NCT03404843

Last Updated: 2020-02-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-07-14
• Study Completion Date: 2018-10-05

Brief 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.

Detailed 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.

Conditions

Cardiovascular Diseases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

Fasudil hydrochloride

Participants will receive a 100 mL intravenous infusion (in 60 minutes) of 60 mg of fasudil hydrochloride + saline prior to measurements of vascular function and ATP release.

Group Type: EXPERIMENTAL

Fasudil Hydrochloride

Intervention Type: DRUG

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.

Saline

Participants will receive a 100 mL intravenous infusion (in 60 minutes) of saline (placebo) prior to measurements of vascular function and ATP release.

Group Type: PLACEBO_COMPARATOR

Saline

Intervention Type: OTHER

100 mL saline bag.

Interventions

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.

Intervention Type: DRUG

Saline

100 mL saline bag.

Intervention Type: OTHER

Other Intervention Names

Placebo

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Colorado State University

OTHER

Sponsor Role: lead

Responsible Party

Frank Dinenno

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Frank Dinenno, PhD

Role: PRINCIPAL_INVESTIGATOR

Colorado State University

Locations

Colorado State University, Dept. of Health and Exercise Science

Fort Collins, Colorado, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

16-6361H

Identifier Type: -

Identifier Source: org_study_id