Clinical trial NCT05278637: GM03 - Platelet RNA Signatures of Aspirin
Official title: DEVELOPMENT OF PROGNOSTIC PLATELET RNA BIOMARKERS TO TAILOR ANTIPLATELET THERAPY
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Platelet Aggregation Inhibitors
Aspirin
Ticagrelor
RNA
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2022-03-14
Enrollment: 135
Sex: ALL
Minimum age (years): 30
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 1. Aspirin 81mg/day x 4 weeks, Aspirin 325mg/day x 4 weeks, Aspirin washout, Ticagrelor 90mg BID x 4 weeks.
2. Aspirin 325mg/day x 4 weeks, Aspirin 81mg/day x 4 weeks, Aspirin washout, Ticagrelor 90mg BID x 4 weeks.
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in expression levels of platelet messenger RNA
timeFrame: Baseline, after every 4 week exposure
Secondary outcomes:
measure: Change in platelet function score
timeFrame: Baseline, 3 hours, after every 4 week exposure
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University
state: North Carolina
Study officials:
affiliation: Duke University
name: Deepak Voora, MD
role: PRINCIPAL_INVESTIGATOR
References: