Impact of Anti-platelet Drug Exposure on Platelet mRNA Splicing in Healthy Subjects

Investigation of Anti-platelet Drug Single Dose Exposure on Platelet mRNA Splicing in Healthy Subjects

The purpose of this pilot study is to determine how the anti-platelet drug, ticagrelor, impacts platelet mRNA splicing after a single loading dose in 10 healthy participants. These results will be valuable in that they will help inform our analysis of platelet RNA splicing after a thrombotic event.

Study Overview

• Status: Withdrawn
• Conditions: Thrombosis; Artery
• Intervention / Treatment: Drug: Ticagrelor Oral Tablet [Brilinta]

Detailed Description

There is nothing known on how differential splicing in platelets is impacted by of P2Y12 inhibition by anti-platelet agents. Consequently, the focus of this longitudinal pilot study will be to determine the impact of a single ticagrelor loading dose (180 mg), our "model" anti-platelet drug, on platelet RNA splicing in 10 healthy individuals.

It will test the hypothesis that ticagrelor exposure does not significantly alter platelet mRNA splicing. It will involve administering a single loading dose (180 mg) of ticagrelor to healthy volunteers.

• Study Type: Observational

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • The George Washington University School of Medicine and Health Sciences
  • Virginia
    • Fairfax, Virginia, United States, 22601
      • Shenandoah University Bernard J. Dunn School of Pharmacy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Healthy patients who meet our inclusion and exclusion criteria

Description

Inclusion Criteria:

• 18 - 70 years-old
• Speak and understand English

Exclusion Criteria:

• History of blood clotting/bleeding disorders
• Current medications that are CYP3A4 inhibitors/inducers
• Current medications that their pharmacokinetics is impacted by ticagrelor (i.e. simvastatin, lovastatin, digoxin) per FDA recommendations.
• Diagnosed with arterial or venous thrombosis
• Active cancer diagnosis
• Pregnant
• Hepatic impairment including active hepatitis infection or cirrhosis
• Current hormonal contraception
• Currently taking aspirin or anti-platelet drugs. If patient has recently taken an NSAID, the last dose should have been discontinued based established criteria

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Healthy Patients; The study design will involve analysis of platelet splicing/activity before and after exposure to a single, 180 mg loading dose of ticagrelor. All subjects will be cardiovascular healthy.	Drug: Ticagrelor Oral Tablet [Brilinta]; A single loading dose of ticagrelor (180 mg) will be administered to each participant in this study.; Other Names: Brilinta

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of the Change in Platelet Activity From Baseline after Drug Administration	As determined by the VerifyNow P2Y12 Assay	Comparison made 2.5 hours following drug administration
Measurement of the Change in Platelet mRNA splicing From Baseline after Drug Administration	As determined by RNAseq analysis	Comparison made 2.5 hours following drug administration
Measurement of Ticagrelor Pharmacokinetics After Drug Administration	Drug and its major metabolite levels will be measured by HPLC	Comparison made 2.5 hours following drug administration

Collaborators and Investigators

• Sponsor: George Washington University
• Collaborators: National Institute on Minority Health and Health Disparities (NIMHD); Shenandoah University; The GW Medical Faculty Associates
• Investigators: Principal Investigator: Travis J O'Brien, PHD, George Washington University

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): April 1, 2020
• Primary Completion (ACTUAL): September 23, 2020
• Study Completion (ACTUAL): September 23, 2020

Study Registration Dates

• First Submitted: September 10, 2019
• First Submitted That Met QC Criteria: September 11, 2019
• First Posted (ACTUAL): September 12, 2019

Study Record Updates

• Last Update Posted (ACTUAL): October 28, 2021
• Last Update Submitted That Met QC Criteria: October 21, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thrombosis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Ticagrelor
• Other Study ID Numbers: NCR191544; U54MD010723 (U.S. NIH Grant/Contract); Pharmacy Faculty Fund (OTHER_GRANT: Bernard J Dunn School of Pharmacy, Shenandoah University); PIND 144269 (OTHER: US FDA IND Exemption)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No IPD will be shared with researchers. Only aggregate data from the study

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No