GM03 - Platelet RNA Signatures of Aspirin

DEVELOPMENT OF PROGNOSTIC PLATELET RNA BIOMARKERS TO TAILOR ANTIPLATELET THERAPY

This study will involve healthy volunteers and patients with Type 2 diabetes. Eligible healthy volunteers will be invited to enroll into one of two protocols (A or B) and eligible patients with diabetes will be enrolled into protocol A.

Study Overview

• Status: Completed
• Conditions: Aspirin; Platelet Aggregation Inhibitors; Ticagrelor; RNA
• Intervention / Treatment: Drug: Aspirin; Drug: Ticagrelor

Detailed Description

Protocol A This will be a randomized, cross-over design comparing low- and high-dose aspirin as well as a non-aspirin platelet inhibitor ticagrelor. This antiplatelet exposure study will be conducted at the DCRU using two separate cohorts: 1) healthy adult volunteers 2) patients with Type 2 diabetes. Subjects within each cohort will but in general will have platelet function testing and biospecimen collection before, four weeks, and eight weeks after low- or high-dose aspirin exposure. Subsequently there will be a period of aspirin washout and a four-week exposure to ticagrelor, a non-aspirin platelet inhibitor. In all subjects and at various time points peripheral blood RNA, purified platelets, DNA, serum, fecal samples and/or plasma will be collected.

Protocol B This will be a single arm study of the platelet inhibitor ticagrelor that is essentially the last two visits of Protocol A. This study will be conducted at the DCRU and will only be open to healthy adult volunteers and patients with Type 2 diabetes. Subjects who elect to participate in this protocol will follow the protocol outlined in Figure 2 and in general will have platelet function testing and biospecimen collection before and four weeks after exposure to ticagrelor, a non-aspirin platelet inhibitor. In all subjects and at various time points (see Figure 2 and Table 2) peripheral blood RNA, purified platelets, DNA, serum, and/ plasma will be collected. In order to align the visits with that of Protocol A, the two visits under this protocol will be labelled V4 and V5.

• Study Type: Interventional
• Enrollment (Actual): 135
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy volunteers
• Age ≥ 30 and ≤ 75
• Non-smoker
• The total number of enrolled females should not exceed 55% of the entire cohort. Therefore, the PI may include/exclude individuals on the basis of gender to achieve an equal balance between men and women.

Exclusion Criteria:

• History of bleeding disorder, gastrointestinal bleeding, intracranial bleeding or known prior gastric ulcer without documented resolution
• Current regular use of antiplatelet agents (aspirin, cilostazol, prasugrel, clopidogrel, dipyridamole, ticagrelor, or ticlopidine), nonsteroidal anti-inflammatory agents (NSAIDs), oral corticosteroids (i.e. prednisone), anticoagulants (warfarin, dabigatran, apixaban, rivaroxaban, enoxaparin)
• Known, severe hepatic impairment
• Surgery within the last 6 months, at the discretion of the PI
• Prior gastric bypass surgery (or equivalent) that interferes with absorbption at the discretion of the PI
• Aspirin allergy or known intolerance to aspirin or ticagrelor.

• Comorbid conditions:

  1. hypertension (requiring prescription medication).
  2. hyperlipidemia (requiring medications)
  3. Type 1 or 2 Diabetes

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Aspirin 81mg/day, Aspirin 325mg/day, Aspirin washout, Ticagrelor 90mg BID	Drug: Aspirin; Aspirin 81mg/day x 4 weeks, Aspirin 325mg/day x 4 weeks. or Aspirin 325mg/day x 4 weeks, Aspirin 81mg/day x 4 weeks.; Drug: Ticagrelor; Ticagrelor 90mg BID x 4 weeks
Active Comparator: Aspirin 325mg/day, Aspirin 81mg/day, Aspirin washout, Ticagrelor 90mg BID	Drug: Aspirin; Aspirin 81mg/day x 4 weeks, Aspirin 325mg/day x 4 weeks. or Aspirin 325mg/day x 4 weeks, Aspirin 81mg/day x 4 weeks.; Drug: Ticagrelor; Ticagrelor 90mg BID x 4 weeks
Active Comparator: Ticagrelor 90mg BID	Drug: Ticagrelor; Ticagrelor 90mg BID x 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in expression levels of platelet messenger RNA	Baseline, after every 4 week exposure

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in platelet function score	Baseline, 3 hours, after every 4 week exposure

Collaborators and Investigators

• Sponsor: Duke University
• Investigators: Principal Investigator: Deepak Voora, MD, Duke University

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2013
• Primary Completion (Actual): December 5, 2016
• Study Completion (Actual): December 5, 2016

Study Registration Dates

• First Submitted: March 4, 2022
• First Submitted That Met QC Criteria: March 4, 2022
• First Posted (Actual): March 14, 2022

Study Record Updates

• Last Update Posted (Actual): March 14, 2022
• Last Update Submitted That Met QC Criteria: March 4, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Aspirin; Ticagrelor
• Other Study ID Numbers: Pro00048621

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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