NCT03404843

Red Blood Cell ATP Release and Vascular Function in Humans

Completed Phase 2 Results posted Last updated 27 February 2020

What this trial tests

Phase 2 trial testing Fasudil Hydrochloride in Cardiovascular Diseases in 31 participants. Completed in 5 October 2018.

Timeline

14 July 2017

Primary endpoint
5 October 2018

5 October 2018

Quick facts

Lead sponsor	Colorado State University
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	triple
Primary purpose	basic science
Enrollment	31
Start date	14 July 2017
Primary completion	5 October 2018
Estimated completion	5 October 2018
Sites	1 location across United States

Drugs / interventions tested

• Fasudil Hydrochloride — full drug profile →
• Saline

Conditions studied

• Cardiovascular Diseases — all drugs for Cardiovascular Diseases →

Sponsor

Colorado State University

Who can join

Adults 18 to 80, any sex, with Cardiovascular Diseases. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Forearm Blood Flow Responses to Hypoxia After Administration of Intervention Primary · Within 4 hours 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%).

Group	Value	95% CI
Young Saline	6.3	± 1.2
Young Fasudil	6.2	± 1.2
Older Saline	2.1	± 0.6
Older Fasudil	8.4	± 1.9

Forearm Blood Flow Responses to Exercise After Administration of Intervention Primary · Within 4 hours 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).

Group	Value	95% CI
Young Saline	315.4	± 31.0
Young Fasudil	283.0	± 25.4
Older Saline	255.3	± 19.9
Older Fasudil	304.2	± 25.2

Change in ATP Release to Hypoxia After Administration of Intervention Primary · Within 4 hours 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%).

Group	Value	95% CI
Young Saline	21.6	± 10.5
Young Fasudil	5.3	± 8.0
Older Saline	5.3	± 5.4
Older Fasudil	17.4	± 13.2

Change in ATP Release to Exercise After Administration of Intervention Primary · Within 4 hours 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).

Group	Value	95% CI
Young Saline	45.6	± 16.8
Young Fasudil	42.2	± 15.1
Older Saline	28.4	± 7.9
Older Fasudil	46.2	± 15.2

Arterial Stiffness After Administration of Intervention Secondary · Immediately following 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.

Group	Value	95% CI
Young Saline	5.4	± 0.2
Young Fasudil	5.2	± 0.2
Older Saline	7.8	± 0.4
Older Fasudil	7.6	± 0.4

Sponsor's own description

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.

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

1. RhoGTPase in Vascular Disease.
   Strassheim D, Gerasimovskaya E, Irwin D, Dempsey EC, et al · · 2019 · cited 61× · PMID 31174369 · DOI 10.3390/cells8060551
2. Rho-Kinase as a Target for Cancer Therapy and Its Immunotherapeutic Potential.
   Kim S, Kim SA, Han J, Kim IS. · · 2021 · cited 50× · PMID 34884721 · DOI 10.3390/ijms222312916
3. Druggable targets in the Rho pathway and their promise for therapeutic control of blood pressure.
   Dee RA, Mangum KD, Bai X, Mack CP, et al · · 2019 · cited 19× · PMID 30189292 · DOI 10.1016/j.pharmthera.2018.09.001
4. The Physiology, Pathology, and Therapeutic Interventions for ROCK Isoforms in Diabetic Kidney Disease.
   Matoba K, Takeda Y, Nagai Y, Sekiguchi K, et al · · 2020 · cited 18× · PMID 33101039 · DOI 10.3389/fphar.2020.585633
5. Fasudil alleviates the vascular endothelial dysfunction and several phenotypes of Fabry disease.
   Choi JB, Seol DW, Do HS, Yang HY, et al · · 2023 · cited 7× · PMID 36755495 · DOI 10.1016/j.ymthe.2023.02.003
6. Exploring the Role of ROCK Inhibition in Corneal Edema Through Crosstalk Between Epithelial and Endothelial Cells.
   Yi LY, Hsieh HH, Lin ZQ, Hung KF, et al · · 2024 · cited 4× · PMID 39534682 · DOI 10.1155/2024/9381303
7. Rho-kinase inhibition reduces systolic blood pressure and forearm vascular resistance in healthy older adults: a double-blind, randomized, placebo-controlled pilot study.
   Bachman NP, Ketelhut NB, Blomquist M, Terwoord JD. · · 2024 · cited 1× · PMID 38888876 · DOI 10.1007/s11357-024-01240-x