Type 2 DiabetesPhase 4CARINGNCT00725127
Chronotherapy with Low-dose Aspirin for Primary Prevention
A Phase 4 study testing aspirin in people with Type 2 Diabetes, run by University of Vigo at 19 sites in Spain.
Trial summary
Brief summary: Aspirin (ASA) has been shown to provide marked benefits in primary and secondary prevention of cardiovascular events. Substantial evidence suggests that low-dose ASA therapy should also be used as a primary prevention strategy in men and women with diabetes who are at high cardiovascular risk. Read more about this study
- Who is it for?
- Ages 50 years and olderHealthy volunteers can take part
- Conditions the study is for
- Type 2 Diabetes
- What is being tested?
- aspirin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3,200 participants
- Where
- 19 sitesSpain
- Study dates
- Oct 2008to 30 Jun 2026
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male or female subjects ≥ 50 years of age.
- Impaired fasting glucose (≥ 100 and < 126 mg/dl) in the last available blood test prior (≤ 3 months) to randomization, or diagnosis of type 2 diabetes prior to randomization.
- All subjects must have at randomization a conventional clinic systolic/diastolic BP < 160/100 mmHg.
- Informed consent to participate in the study prior to any study procedures.
Who cannot join
- Known or suspected contraindications, including history of allergy to ASA.
- Uncontrolled essential hypertension of Grade 2-3, i.e., systolic BP ≥ 160 mmHg and/or diastolic BP ≥ 100 mmHg before randomization.
- Evidence of a secondary form of hypertension, to include coarctation of the aorta, hyperaldosteronism, renal artery stenosis, or pheochromocytoma.
- Known Keith-Wagener grade III or IV hypertensive retinopathy.
- History of hypertensive encephalopathy, cerebrovascular event, transient ischemic cerebral attack, or myocardial infarction prior to randomization.
- Type 1 diabetes mellitus.
Show all 19Show fewer
- History of heart failure.
- Second or third degree heart block without a pacemaker.
- Concomitant unstable angina pectoris.
- Concomitant potentially life threatening arrhythmia or symptomatic arrhythmia.
- Clinically significant valvular heart disease.
- Evidence of hepatic disease as determined by one of the following: ALT or AST values > 2 x UNL known before randomization, a history of hepatic encephalopathy, history of esophageal varices, or history of portocaval shunt.
- Diagnosis of chronic kidney disease prior to randomization.
- History of malignancy including leukemia and lymphoma (but not basal cell skin cancer), or any other severe, life-threatening disease within the past five years.
- Any previous history of a systemic autoimmune disease.
- History of drug or alcohol abuse within the last two years.
- Use of any disallowed concomitant medication.
- Inability to communicate and comply with all study requirements.
- Persons directly involved in the execution of this protocol.
Trial locations and contacts
19 sites in 1 country.
19 sites in 1 country
Spain19 sites
CS A Estrada
A Estrada, Pontevedra, 26680
CS Baiona
Baiona, Pontevedra, 36300
CS Bueu
Bueu, Pontevedra, 36930
CS Friol
Friol, Lugo, 27220
CS A Guarda
La Guardia, Pontevedra, 36780
CS Fingoi
Lugo, Lugo, 27002
CS Valmiñor
Nigrán, Pontevedra, 36250
CS Panxón
Nigrán, Pontevedra, 36340
Complexo Hospitalario Universitario de Ourense
Ourense, Orense, 32005
CS Lerez
Pontevedra, Pontevedra, 36156
CS Tomiño
Tomiño, Pontevedra, 36200
Bioengineering & Chronobilogy Labs., University of Vigo
Vigo, Pontevedra, 36200
CS Calle Cuba
Vigo, Pontevedra, 36202
CS A Doblada
Vigo, Pontevedra, 36205
CS Coia
Vigo, Pontevedra, 36209
CS Sardoma
Vigo, Pontevedra, 36214
CS Teis
Vigo, Pontevedra, 36216
CS Vilaboa
Vilaboa, Pontevedra, 36141
CS San Roque
Vilagarcía de Arousa, Pontevedra, 36600
About this study
Official title: Chronotherapy with Low-dose Aspirin for Primary Prevention of Cardiovascular Events in Subjects with Impaired Fasting Glucose or Diabetes (CARING Study).
Brief summary:
Aspirin (ASA) has been shown to provide marked benefits in primary and secondary prevention of cardiovascular events. Substantial evidence suggests that low-dose ASA therapy should also be used as a primary prevention strategy in men and women with diabetes who are at high cardiovascular risk. On the other hand, there is current evidence on the potential benefits of low-dose ASA therapy in subjects with impaired fasting glucose, including those with metabolic syndrome. Most important, previous laboratory animal and clinical trial research convincingly demonstrates administration time-dependent (with reference to circadian rhythms) effects of ASA. Thus, the effects of ASA upon lipoperoxides, b-adrenergic receptors, and blood pressure (BP) in clinically healthy subjects depend on the circadian timing of ASA administration. The administration-time-dependent influence of ASA on BP was previously demonstrated in a randomized trial on healthy women and other independent double-blind, randomized, placebo-controlled clinical trials conducted, first, on clinically healthy subjects, a second one on normotensive and hypertensive subjects, a third one on pregnant women at high risk for preeclampsia and a fourth one in previously untreated patients with mild hypertension. The findings of these BP studies are consistent; BP-lowering effect of low-dose ASA is achieved when administered at bedtime but not upon awakening.
In keeping with the chronopharmacological effects of ASA and the previous findings suggesting that ASA at low dose may exert a potential beneficial effect on BP, endothelium function and cardiovascular function, this prospective, randomized, parallel-arm study will investigate the potential influence of ASA on the primary prevention of cardiovascular, cerebrovascular and renal events in subjects with either impaired fasting glucose (≥ 100 mg/dl) or previous diagnosis of type 2 diabetes mellitus, who will receive low-dose ASA (100 mg/day) at different circadian times (upon awakening or at bedtime) in relation to their rest-activity cycle.
- Conditions
- Type 2 Diabetes
- Being tested
- aspirin
- Keywords
- Aspirin, Chronotherapy, Primary prevention, Impaired fasting glucose, Type 2 diabetes, Total mortality, Myocardial infarction, Stroke, Angina pectoris, Chronic kidney disease
- Medical subject headings
- Diabetes Mellitus, Type 2, Myocardial Infarction, Stroke, Angina Pectoris, Renal Insufficiency, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
aspirinDrug
Also called Aspirin on awakening
100 mg/day upon awakening for five years
aspirinDrug
Also called Aspirin at bedtime
100 mg/day at bedtime for five years
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | 100 mg/day ASA upon awakening. Receives: Drug: aspirin |
| 2 | Active comparator | 100 mg/day ASA at bedtime Receives: Drug: aspirin |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the effects of awakening vs. bedtime 100 mg/day ASA administration in subjects with impaired fasting glucose or type 2 diabetes on primary prevention of cardiovascular, cerebrovascular and renal fatal, and non-fatal events.
Measured: Five years
Secondary outcomes (8)
To evaluate the effects of awakening vs. bedtime 100 mg/day ASA administration on primary prevention of cardiovascular fatal and non-fatal events (including cardiovascular death, myocardial infarction, angina pectoris, and coronary revascularization).
Measured: Five years
To evaluate the effects of awakening vs. bedtime 100 mg/day ASA administration on primary prevention of cerebrovascular fatal and non-fatal events (including hemorrhagic stroke, ischemic stroke, and transient ischemic attack).
Measured: Five years
To evaluate the effects of awakening vs. bedtime 100 mg/day ASA administration on primary prevention of chronic kidney disease and/or congestive heart failure, and/or peripheral artery disease.
Measured: Five years
To demonstrate that 100 mg/day ASA at bedtime offers a similar safety profile than 100 mg/day ASA upon awakening
Measured: Five years
To demonstrate that compliance with 100 mg/day ASA at bedtime is similar to that with 100 mg/day ASA upon awakening.
Measured: Five years
To evaluate, for all previous objectives, potential gender differences in the benefits of low-dose ASA for primary prevention.
Measured: Five years
To evaluate, for all previous objectives, potential differences in the benefits of low-dose ASA for primary prevention between patients with and without diabetes.
Measured: Five years
To evaluate, for all previous objectives, potential differences in the benefits of low-dose ASA for primary prevention between subjects with and without metabolic syndrome.
Measured: Five years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2008 (estimated)
- Study startOct 2008
- Primary completion31 Dec 2025 (estimated)
- Study completion30 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 3,200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Vigo
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ramon C. Hermida, University of Vigo
- Investigators
- Ramon C Hermida, PhD, Study director, University of Vigo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00725127
- Sponsor's protocol ID
- CARING-2008/1
- Other IDs
- 2008-002669-30, 2008
- Acronym
- CARING
- Status last verified
- Dec 2024
- First submitted
- 28 Jul 2008
- Last updated
- 6 Dec 2024
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 6 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Chronotherapy with Low-dose Aspirin for Primary Prevention of Cardiovascular Events in Subjects with Impaired Fasting Glucose or Diabetes (CARING Study).
- ClinicalTrials.gov ID
- NCT00725127
- Acronym / sponsor ID
- CARING / CARING-2008/1
- Conditions
- Type 2 Diabetes
- Keywords
- Aspirin, Chronotherapy, Primary prevention, Impaired fasting glucose, Type 2 diabetes, Total mortality, Myocardial infarction, Stroke
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 3,200 participants (estimated)
- Lead sponsor
- University of VigoUniversity, hospital or other
- Study start
- Oct 2008 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 30 Jun 2026 (estimated)
- First posted
- 30 Jul 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Brief summary:
Aspirin (ASA) has been shown to provide marked benefits in primary and secondary prevention of cardiovascular events. Substantial evidence suggests that low-dose ASA therapy should also be used as a primary prevention strategy in men and women with diabetes who are at high cardiovascular risk. On the other hand, there is current evidence on the potential benefits of low-dose ASA therapy in subjects with impaired fasting glucose, including those with metabolic syndrome. Most important, previous laboratory animal and clinical trial research convincingly demonstrates administration time-dependent (with reference to circadian rhythms) effects of ASA. Thus, the effects of ASA upon lipoperoxides, b-adrenergic receptors, and blood pressure (BP) in clinically healthy subjects depend on the circadian timing of ASA administration. The administration-time-dependent influence of ASA on BP was previously demonstrated in a randomized trial on healthy women and other independent double-blind, randomized, placebo-controlled clinical trials conducted, first, on clinically healthy subjects, a second one on normotensive and hypertensive subjects, a third one on pregnant women at high risk for preeclampsia and a fourth one in previously untreated patients with mild hypertension. The findings of these BP studies are consistent; BP-lowering effect of low-dose ASA is achieved when administered at bedtime but not upon awakening.
In keeping with the chronopharmacological effects of ASA and the previous findings suggesting that ASA at low dose may exert a potential beneficial effect on BP, endothelium function and cardiovascular function, this prospective, randomized, parallel-arm study will investigate the potential influence of ASA on the primary prevention of cardiovascular, cerebrovascular and renal events in subjects with either impaired fasting glucose (≥ 100 mg/dl) or previous diagnosis of type 2 diabetes mellitus, who will receive low-dose ASA (100 mg/day) at different circadian times (upon awakening or at bedtime) in relation to their rest-activity cycle.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: aspirin100 mg/day ASA upon awakening. |
| 2 | Active comparator | Drug: aspirin100 mg/day ASA at bedtime |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Male or female subjects ≥ 50 years of age.
- Impaired fasting glucose (≥ 100 and < 126 mg/dl) in the last available blood test prior (≤ 3 months) to randomization, or diagnosis of type 2 diabetes prior to randomization.
- All subjects must have at randomization a conventional clinic systolic/diastolic BP < 160/100 mmHg.
- Informed consent to participate in the study prior to any study procedures.
Key exclusion criteria (19 listed)
- Known or suspected contraindications, including history of allergy to ASA.
- Uncontrolled essential hypertension of Grade 2-3, i.e., systolic BP ≥ 160 mmHg and/or diastolic BP ≥ 100 mmHg before randomization.
- Evidence of a secondary form of hypertension, to include coarctation of the aorta, hyperaldosteronism, renal artery stenosis, or pheochromocytoma.
- Known Keith-Wagener grade III or IV hypertensive retinopathy.
- History of hypertensive encephalopathy, cerebrovascular event, transient ischemic cerebral attack, or myocardial infarction prior to randomization.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| aspirinAlso: Aspirin on awakening100 mg/day upon awakening for five years | Drug | 1 |
| aspirinAlso: Aspirin at bedtime100 mg/day at bedtime for five years | Drug | 2 |
Primary outcome
To evaluate the effects of awakening vs. bedtime 100 mg/day ASA administration in subjects with impaired fasting glucose or type 2 diabetes on primary prevention of cardiovascular, cerebrovascular and renal fatal, and non-fatal events.
Time frame: Five years
8 secondary outcomes
To evaluate the effects of awakening vs. bedtime 100 mg/day ASA administration on primary prevention of cardiovascular fatal and non-fatal events (including cardiovascular death, myocardial infarction, angina pectoris, and coronary revascularization).
Time frame: Five years
To evaluate the effects of awakening vs. bedtime 100 mg/day ASA administration on primary prevention of cerebrovascular fatal and non-fatal events (including hemorrhagic stroke, ischemic stroke, and transient ischemic attack).
Time frame: Five years
To evaluate the effects of awakening vs. bedtime 100 mg/day ASA administration on primary prevention of chronic kidney disease and/or congestive heart failure, and/or peripheral artery disease.
Time frame: Five years
To demonstrate that 100 mg/day ASA at bedtime offers a similar safety profile than 100 mg/day ASA upon awakening
Time frame: Five years
To demonstrate that compliance with 100 mg/day ASA at bedtime is similar to that with 100 mg/day ASA upon awakening.
Time frame: Five years
To evaluate, for all previous objectives, potential gender differences in the benefits of low-dose ASA for primary prevention.
Time frame: Five years
To evaluate, for all previous objectives, potential differences in the benefits of low-dose ASA for primary prevention between patients with and without diabetes.
Time frame: Five years
To evaluate, for all previous objectives, potential differences in the benefits of low-dose ASA for primary prevention between subjects with and without metabolic syndrome.
Time frame: Five years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Dec 2024.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ramon C Hermida, PhD study director
University of Vigo
19 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing aspirin in people with Type 2 Diabetes, run by University of Vigo at 19 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 6 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To evaluate the effects of awakening vs. bedtime 100 mg/day ASA administration in subjects with impaired fasting glucose or type 2 diabetes on primary prevention of cardiovascular, cerebrovascular and renal fatal, and non-fatal events. (time frame: Five years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Dec 2024.