Aspirin Dosing for Type 2 Diabetes

(APPEASEDII Trial)

Recruiting at 1 trial location

Overseen By Marie Lordkipanidzé B. Pharm, Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Montreal Heart Institute

Must be taking: Oral antihyperglycemics, Insulin

Must not be taking: Anticoagulants, Antiplatelets, NSAIDs, Steroids

Disqualifiers: Atherosclerotic disease, Dialysis, Hepatic insufficiency, GI bleeding, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how people with type 2 diabetes respond to different aspirin regimens. Initially, participants will take a low dose of enteric-coated aspirin (which dissolves in the intestines) to assess its effect on platelet function, crucial for blood clotting. If the initial dose proves ineffective, participants will try different dosing schedules to identify the most effective one. Individuals who haven't recently used aspirin and are managing type 2 diabetes with medication or have specific blood sugar levels might be suitable candidates. The goal is to determine the best aspirin regimen for future, larger trials. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking advancements in diabetes care.

Will I have to stop taking my current medications?

The trial requires that participants do not take aspirin regularly before joining, and those on certain medications like anticoagulants, antiplatelet agents, NSAIDs, or systemic steroids cannot participate. If you're on these medications, you may need to stop them to join the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that aspirin is usually safe for people with type 2 diabetes, but several considerations are important. Some studies have found that aspirin can lower the risk of serious heart problems in people with diabetes. However, daily aspirin use can increase the risk of bleeding, particularly for those with diabetes.

One study found that people with type 2 diabetes who took low-dose aspirin experienced fewer serious heart issues compared to those who didn't take aspirin. However, real-world data suggests that people with diabetes who take aspirin daily might experience more bleeding than those who don't.

While aspirin can be beneficial, it also carries risks. Always consult a healthcare provider before starting any new medication, especially if there are concerns about bleeding or other side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these aspirin treatments for type 2 diabetes because they explore different dosing strategies that might offer new benefits. Unlike the usual low-dose aspirin used primarily for heart health in diabetic patients, these trials investigate the effects of enteric-coated aspirin (EC ASA) in various doses and forms, including 81 mg twice daily, 162 mg once daily, and chewable 40 mg twice daily. These variations may improve aspirin's effectiveness in reducing inflammation and cardiovascular risks associated with diabetes. By potentially optimizing dosage and delivery methods, these treatments could offer quicker or more targeted results compared to standard aspirin regimens.

What evidence suggests that this trial's aspirin regimens could be effective for type 2 diabetes?

This trial will compare different dosing regimens of aspirin for people with type 2 diabetes. Research has shown that aspirin affects people with type 2 diabetes in various ways. Studies indicate that aspirin can help prevent serious heart problems in people with diabetes, but it may also increase the risk of bleeding. One study found that aspirin use reduced the risk of death in people with heart issues. However, another trial showed that a high dose of aspirin did not lower major heart problems in people with diabetes. These mixed results suggest that aspirin's effectiveness depends on the dose and the individual's health condition. ^{2 5 6 7 8}

Who Is on the Research Team?

Guillaume Marquis Gravel, MD, MSc

Principal Investigator

ICM Co. Ltd.

Are You a Good Fit for This Trial?

Adults with type 2 diabetes who haven't taken aspirin regularly in the past 3 months can join. They must be willing to attend all study visits and not have any planned major surgeries, bleeding disorders, severe liver issues, active cancer, chronic inflammatory diseases needing anti-inflammatory drugs, high-risk GI bleeding conditions or need for dialysis.

Inclusion Criteria

I haven't taken ASA regularly in the last 3 months or at all in the last 2 weeks.

I have type 2 diabetes.

I am willing to attend all required study visits.

Exclusion Criteria

I am on regular medication for a chronic inflammatory condition.

I have had blood cancer or a condition that affects how my blood cells form.

Your blood platelet count or hemoglobin levels are not within the normal range.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Run-in

Participants receive 80 mg of enteric-coated aspirin daily for 7 days to assess initial response

1 week

2 visits (in-person)

Randomized Treatment

Participants are randomized to one of three ASA regimens for 7 days each, with washout periods in between

3 weeks (plus washout periods)

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Aspirin

Trial Overview The trial is testing how different doses and forms of aspirin affect blood platelet function in people with type 2 diabetes over a week. It compares daily enteric-coated aspirin (81 mg twice or 162 mg once) versus chewable aspirin (40 mg twice), focusing on which regimen best prevents platelets from clumping together.

How Is the Trial Designed?

Group I: chewable ASA 40 mg twice daily for 7 days Experimental Treatment 1 Intervention

chewable ASA 40 mg twice daily for 7 days

Group II: EC ASA 81 mg twice daily for 7 days Experimental Treatment 1 Intervention

EC ASA 81 mg twice daily for 7 days

Group III: EC ASA 162 mg once daily for 7 days Experimental Treatment 1 Intervention

EC ASA 162 mg once daily for 7 days

Aspirin is already approved in European Union, United States, Canada, China for the following indications:

Approved in European Union as Aspirin for:

• Pain relief
• Fever reduction
• Inflammation
• Cardiovascular disease prevention
• Preeclampsia prevention

Approved in United States as Aspirin for:

• Pain relief
• Fever reduction
• Inflammation
• Cardiovascular disease prevention
• Preeclampsia prevention

Approved in Canada as Aspirin for:

• Pain relief
• Fever reduction
• Inflammation
• Cardiovascular disease prevention
• Preeclampsia prevention

Approved in China as Aspirin for:

• Pain relief
• Fever reduction
• Inflammation
• Cardiovascular disease prevention

Who Is Running the Clinical Trial?

Montreal Heart Institute

Lead Sponsor

Trials

125

Recruited

85,400+

Heart and Stroke Foundation of Canada

Collaborator

Trials

131

Recruited

72,600+

Institut de Recherches Cliniques de Montreal

Collaborator

Trials

72

Recruited

10,300+

Published Research Related to This Trial

The new buffered acetylsalicylic acid (ASA) formulation showed equivalent bioavailability to the plain ASA tablet, with a relative bioavailability of 102.49%, indicating it can be used interchangeably with the standard formulation.

Buffered ASA reached peak plasma concentration significantly faster (28 minutes) compared to the plain tablet (38 minutes), suggesting quicker absorption and potentially faster onset of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic study of a new oral buffered acetylsalicylic acid (ASA) formulation in comparison with plain ASA in healthy volunteers. Viganò, G., Garagiola, U., Gaspari, F.[2013]

In a study involving 2539 patients with type 2 diabetes, low-dose aspirin did not reduce the risk of cardiovascular events over a median follow-up of 10.3 years, indicating it may not be effective for primary prevention in this population.

However, the use of low-dose aspirin was associated with an increased risk of gastrointestinal bleeding, with 2% of patients in the aspirin group experiencing this side effect compared to 0.9% in the no-aspirin group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-Dose Aspirin for Primary Prevention of Cardiovascular Events in Patients With Type 2 Diabetes Mellitus: 10-Year Follow-Up of a Randomized Controlled Trial. Saito, Y., Okada, S., Ogawa, H., et al.[2020]

In a study involving 2539 patients with type 2 diabetes over a median follow-up of 4.37 years, low-dose aspirin did not significantly reduce the overall risk of atherosclerotic events compared to a nonaspirin group.

However, the aspirin group had a significantly lower incidence of fatal coronary and cerebrovascular events, suggesting that while aspirin may not reduce all cardiovascular risks, it could be beneficial in preventing severe outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose aspirin for primary prevention of atherosclerotic events in patients with type 2 diabetes: a randomized controlled trial. Ogawa, H., Nakayama, M., Morimoto, T., et al.[2023]

In a study involving healthy volunteers who took varying doses of acetylsalicylic acid (ASA) for one week, all doses significantly inhibited platelet function and increased bleeding times, indicating its effectiveness in thrombosis prophylaxis.

The research found that a daily dose of around 100 mg of ASA maximized the effects on platelet function and bleeding time, suggesting that higher doses do not provide additional benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of different doses of some acetylsalicylic acid formulations on platelet function and bleeding times in healthy subjects. McLeod, LJ., Roberts, MS., Cossum, PA., et al.[2019]

In a study involving 38 healthy volunteers and 38 type 2 diabetic patients, it was found that diabetic patients had significantly higher aspirin esterase activity, leading to faster hydrolysis of aspirin, which may reduce its effectiveness as an antiplatelet drug.

The increased degradation of aspirin in diabetic patients was linked to a weaker response of their platelets to the medication, suggesting that diabetes may affect the efficacy of aspirin therapy in preventing cardiovascular events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased blood plasma hydrolysis of acetylsalicylic acid in type 2 diabetic patients: a role of plasma esterases. Gresner, P., Dolník, M., Waczulíková, I., et al.[2017]

Aspirin (ASA) significantly reduced urinary 11-dehydro-thromboxane B2 levels by about 71.5% in patients with type 2 diabetes and 75.1% in healthy controls, indicating its effectiveness in inhibiting platelet activation through COX-1 inhibition.

Despite the reduction in thromboxane levels, many patients with type 2 diabetes were identified as 'poor responders' to ASA, suggesting that oxidative stress may counteract the effects of ASA and maintain platelet function, highlighting a potential challenge in treating this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aspirin insensitive thromboxane generation is associated with oxidative stress in type 2 diabetes mellitus. Ames, PR., Batuca, JR., Muncy, IJ., et al.[2013]

In a study involving 25 patients with type 2 diabetes and vascular complications, taking low-dose aspirin twice daily (75 mg BID) showed improved platelet response compared to once daily dosing (75 mg OD) and was more effective than higher doses (320 mg OD) in reducing platelet aggregation.

The findings suggest that twice daily dosing of aspirin may enhance its effectiveness in managing platelet activity in high-risk patients with type 2 diabetes, warranting further research to see if this dosing strategy can lead to better clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Twice daily dosing of aspirin improves platelet inhibition in whole blood in patients with type 2 diabetes mellitus and micro- or macrovascular complications. Spectre, G., Arnetz, L., Östenson, CG., et al.[2013]

From 1997 to 2000, only 2.1% to 5.7% of diabetic patients over 30 with cardiovascular risk factors were prescribed low-dose aspirin (ASA) for primary prevention, indicating very low adherence to the American Diabetes Association (ADA) guidelines.

Factors that increased the likelihood of receiving ASA included being male, older than 44, having cardiovascular risk factors, and receiving preventative counseling, highlighting the need for targeted efforts to improve adherence rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aspirin for primary prevention in patients with diabetes mellitus. Nguyen, KX., Marinac, JS., Sun, C.[2013]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa1804988

Effects of Aspirin for Primary Prevention in Persons with ... Aspirin use prevented serious vascular events in persons who had diabetes and no evident cardiovascular disease at trial entry, but it also caused major ...

2. diabetesjournals.org diabetesjournals.org/care/article/47/1/81/153638/Comparative-Effectiveness-of-Aspirin-Dosing-in

Comparative Effectiveness of Aspirin Dosing in ... Patients with versus without DM had higher rates of the composite cardiovascular outcome (9.6% vs. 5.9%; P < 0.001) and bleeding events (0.78% ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3208465/

Effect of Aspirin Dose on Mortality and Cardiovascular ... Aspirin use was associated with a significantly lower risk of mortality (RR: 0.82; 95% CI: 0.69–0.98; p = 0.03) in 13 secondary prevention studies (I2 = 27%), ...

4. ahajournals.org ahajournals.org/doi/10.1161/JAHA.118.010033

Aspirin Use and Cardiovascular Outcome in Patients With ... Our study suggests that aspirin is beneficial in patients with type 2 diabetes mellitus and heart failure, aged ≥55 years, and with no previous ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S1538783622167784

Is aspirin effective in diabetic patients? No In the ETDRS trial of 3711 diabetics followed for 7 years, primary prevention with ASA 650 mg daily did not reduce the incidence of major cardiovascular events ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2663598/

Aspirin use and risk of type 2 diabetes in apparently ... Our data suggest a small but not significant decrease in the risk of diabetes during 5 years of randomized comparison of 325 mg of aspirin every other day.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03341117

Acetylsalicylic Acid and Type 2 Diabetes Mellitus A randomized, double blind placebo controlled clinical trial was carried out in 21 adult patients with type 2 diabetes. Acetylsalicylic acid 300mg/d was ...

8. healthline.com healthline.com/health/diabetes/aspirin-diabetes

Aspirin and Diabetes: Safety, Heart Health, and More Researchers noted that real-world data has shown higher rates of bleeding in people with diabetes who take daily aspirin, even if this review ...