AtherosclerosisRIPPLENCT04073810
Residual Inflammation and Plaque Progression Long-term Evaluation
An observational study of Atherosclerosis and Myocardial Infarction, run by University of Cambridge at 1 site in United Kingdom.
Trial summary
Inflammation drives atherosclerotic plaque rupture triggering most acute coronary syndromes. Despite advances in diagnosis and management of atherosclerosis, patients with myocardial infarction (MI) remain at increased risk of recurrent events. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Atherosclerosis, Myocardial Infarction, Coronary Artery Disease
- What is being tested?
- PET imaging, Coronary CT angiography and Cardiac MRI
- How many people
- 40 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Oct 2020to 1 Apr 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
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 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with recent myocardial infarction and medically managed non-culprit coronary artery disease
Who may be able to join
- Male or female participants >18 years old
- Able to give written, informed consent and to lie flat
- First-presentation of myocardial infarction within ~2 weeks
- At least mild non-culprit coronary artery disease on angiography, managed medically
Who cannot join
- Women of child bearing potential not using adequate contraception
- Contrast allergy or contrast-nephropathy
- Uncontrolled atrial fibrillation
- Chronic kidney disease (eGFR <30 mL/min/1.73 m2)
- Any medical condition, in the opinion of the investigator, that prevents the participant from lying flat during scanning, or from participating in the study
- Uncontrolled chronic inflammatory disorder
Show all 11Show fewer
- History of recent malignancy deemed relevant to the study by the investigator
- Current use of systemic corticosteroids
- Previous coronary artery bypass grafting surgery (CABG) or percutaneous coronary intervention (PCI) before the index event
- Contraindication to coronary angiography
- Requires CABG or staged non-culprit artery PCI
Trial locations and contacts
1 site in 1 country.
About this study
Inflammation drives atherosclerotic plaque rupture triggering most acute coronary syndromes. Despite advances in diagnosis and management of atherosclerosis, patients with myocardial infarction (MI) remain at increased risk of recurrent events. The RIPPLE study aims to examine the relationship between residual coronary inflammation detected by 68Ga-DOTATATE PET in patients treated for MI to long-term plaque progression measured by CT coronary angiography (CTCA). The association between infarct-related myocardial 68Ga-DOTATATE PET and myocardial function and viability will also be assessed.
Read the detailed description
While vascular inflammation can be detected using 18F-FDG PET, this method lacks inflammatory cell specificity and is unreliable for coronary imaging because of high background signals from the myocardium. Upregulation of somatostatin receptor subtype-2 (SST2) occurs in activated macrophages, offering a novel inflammation imaging target. 68Ga-DOTATATE, an SST2 PET tracer with low myocardial binding, shows promise for imaging coronary inflammation. Having previously demonstrated increased 68Ga-DOTATATE signals in coronary atherosclerotic lesions post-MI, we now aim to study the natural history of residual arterial inflammation in non-culprit arteries and better understand how 68Ga-DOTATATE signals relate to plaque morphology, progression and rupture. Residual infarct-related myocardial inflammation and its association with ischemic myocardial remodelling will also be examined.
- Being tested
- PET imaging, Coronary CT angiography, Cardiac MRI
- Medical subject headings
- Atherosclerosis, Myocardial Infarction, Coronary Artery Disease, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PET imagingDiagnostic test
Coronary 68Ga-DOTATATE PET-MRI or PET-CT at baseline and 3 months
Coronary CT angiographyDiagnostic test
CTCA at baseline and 2 years
Cardiac MRIDiagnostic test
Cardiac MRI at 1 year
| Study group | Role | What they receive |
|---|---|---|
| Myocardial infarction | Patients with recent MI Receives: Diagnostic Test: PET imaging; Diagnostic Test: Coronary CT angiography; Diagnostic Test: Cardiac MRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
68Ga-DOTATATE PET vs. plaque progression
Comparison of non-culprit coronary artery 68Ga-DOTATATE tissue-to-blood ratio at 12 weeks post-MI in patients with plaque progression (changes in low attenuation plaque volume and total atheroma volume) after 2 years measured by CTCA versus those without
Measured: 2 years
Secondary outcomes (5)
68Ga-DOTATATE PET vs. CTCA-defined plaque morphology
Comparison of coronary 68Ga-DOTATATE imaging to changes in plaque morphology measured by CTCA
Measured: 2 years
68Ga-DOTATATE PET vs. intravascular imaging
Comparison of 68Ga-DOTATATE imaging to plaque morphology defined by high-resolution intravascular imaging performed during invasive coronary angiography
Measured: Baseline
68Ga-DOTATATE PET vs. hsCRP
Comparison of 68Ga-DOTATATE PET to high-sensitivity C-reactive protein
Measured: 2 years
68Ga-DOTATATE PET vs left ventricular myocardial function
Comparison of myocardial 68Ga-DOTATATE PET to left ventricular size and function
Measured: 1 year
68Ga-DOTATATE PET vs myocardial tissue characterization
Comparison of myocardial 68Ga-DOTATATE PET to myocardial scarring and oedema
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2019
- Study start1 Oct 2020
- Primary completion1 Dec 2024 (estimated)
- Study completion1 Apr 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for AtherosclerosisStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Cambridge
- Sponsor type
- University, hospital or other
- Collaborators
- Cambridge University Hospitals NHS Foundation Trust, Wellcome Trust
- Responsible party
- Principal investigator, Jason Tarkin, University of Cambridge
- Investigators
- Jason M Tarkin, MBBS PhD, Principal investigator, University of Cambridge
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04073810
- Sponsor's protocol ID
- A095007 (RIPPLE)
- Acronym
- RIPPLE
- Status last verified
- Jul 2024
- First submitted
- 27 Aug 2019
- Last updated
- 19 Jul 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Tarkin JM, Joshi FR, Evans NR, Chowdhury MM, Figg NL, Shah AV, Starks LT, Martin-Garrido A, Manavaki R, Yu E, Kuc RE, Grassi L, Kreuzhuber R, Kostadima MA, Frontini M, Kirkpatrick PJ, Coughlin PA, Gopalan D, Fryer TD, Buscombe JR, Groves AM, Ouwehand WH, Bennett MR, Warburton EA, Davenport AP, Rudd JH. Detection of Atherosclerotic Inflammation by 68Ga-DOTATATE PET Compared to [18F]FDG PET Imaging. J Am Coll Cardiol. 2017 Apr 11;69(14):1774-1791. doi: 10.1016/j.jacc.2017.01.060.
PubMed 28385306Pedersen SF, Sandholt BV, Keller SH, Hansen AE, Clemmensen AE, Sillesen H, Hojgaard L, Ripa RS, Kjaer A. 64Cu-DOTATATE PET/MRI for Detection of Activated Macrophages in Carotid Atherosclerotic Plaques: Studies in Patients Undergoing Endarterectomy. Arterioscler Thromb Vasc Biol. 2015 Jul;35(7):1696-703. doi: 10.1161/ATVBAHA.114.305067. Epub 2015 May 14.
PubMed 25977567Rominger A, Saam T, Vogl E, Ubleis C, la Fougere C, Forster S, Haug A, Cumming P, Reiser MF, Nikolaou K, Bartenstein P, Hacker M. In vivo imaging of macrophage activity in the coronary arteries using 68Ga-DOTATATE PET/CT: correlation with coronary calcium burden and risk factors. J Nucl Med. 2010 Feb;51(2):193-7. doi: 10.2967/jnumed.109.070672. Epub 2010 Jan 15.
PubMed 20080898Corovic A, Wall C, Nus M, Gopalan D, Huang Y, Imaz M, Zulcinski M, Peverelli M, Uryga A, Lambert J, Bressan D, Maughan RT, Pericleous C, Dubash S, Jordan N, Jayne DR, Hoole SP, Calvert PA, Dean AF, Rassl D, Barwick T, Iles M, Frontini M, Hannon G, Manavaki R, Fryer TD, Aloj L, Graves MJ, Gilbert FJ, Dweck MR, Newby DE, Fayad ZA, Reynolds G, Morgan AW, Aboagye EO, Davenport AP, Jorgensen HF, Mallat Z, Bennett MR, Peters JE, Rudd JHF, Mason JC, Tarkin JM. Somatostatin Receptor PET/MR Imaging of Inflammation in Patients With Large Vessel Vasculitis and Atherosclerosis. J Am Coll Cardiol. 2023 Jan 31;81(4):336-354. doi: 10.1016/j.jacc.2022.10.034.
PubMed 36697134
Study at a glance
From the registry record, last updated by the sponsor on 19 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Residual Inflammation and Plaque Progression Long-term Evaluation
- ClinicalTrials.gov ID
- NCT04073810
- Acronym / sponsor ID
- RIPPLE / A095007 (RIPPLE)
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- University of CambridgeUniversity, hospital or other
- Collaborators
- Cambridge University Hospitals NHS Foundation Trust, Wellcome Trust
- Study start
- 1 Oct 2020 (actual)
- Primary completion
- 1 Dec 2024 (estimated)
- Study completion
- 1 Apr 2025 (estimated)
- First posted
- 29 Aug 2019 (actual)
- 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.
Inflammation drives atherosclerotic plaque rupture triggering most acute coronary syndromes. Despite advances in diagnosis and management of atherosclerosis, patients with myocardial infarction (MI) remain at increased risk of recurrent events. The RIPPLE study aims to examine the relationship between residual coronary inflammation detected by 68Ga-DOTATATE PET in patients treated for MI to long-term plaque progression measured by CT coronary angiography (CTCA). The association between infarct-related myocardial 68Ga-DOTATATE PET and myocardial function and viability will also be assessed.
Detailed description
While vascular inflammation can be detected using 18F-FDG PET, this method lacks inflammatory cell specificity and is unreliable for coronary imaging because of high background signals from the myocardium. Upregulation of somatostatin receptor subtype-2 (SST2) occurs in activated macrophages, offering a novel inflammation imaging target. 68Ga-DOTATATE, an SST2 PET tracer with low myocardial binding, shows promise for imaging coronary inflammation. Having previously demonstrated increased 68Ga-DOTATATE signals in coronary atherosclerotic lesions post-MI, we now aim to study the natural history of residual arterial inflammation in non-culprit arteries and better understand how 68Ga-DOTATATE signals relate to plaque morphology, progression and rupture. Residual infarct-related myocardial inflammation and its association with ischemic myocardial remodelling will also be examined.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Myocardial infarction | – | Diagnostic Test: PET imaging, Diagnostic Test: Coronary CT angiography, Diagnostic Test: Cardiac MRIPatients with recent MI |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with recent myocardial infarction and medically managed non-culprit coronary artery disease
Key inclusion criteria (4 listed)
- Male or female participants >18 years old
- Able to give written, informed consent and to lie flat
- First-presentation of myocardial infarction within ~2 weeks
- At least mild non-culprit coronary artery disease on angiography, managed medically
Key exclusion criteria (11 listed)
- Women of child bearing potential not using adequate contraception
- Contrast allergy or contrast-nephropathy
- Uncontrolled atrial fibrillation
- Chronic kidney disease (eGFR <30 mL/min/1.73 m2)
- Any medical condition, in the opinion of the investigator, that prevents the participant from lying flat during scanning, or from participating in the study
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 |
|---|---|---|
| PET imagingCoronary 68Ga-DOTATATE PET-MRI or PET-CT at baseline and 3 months | Diagnostic test | Myocardial infarction |
| Coronary CT angiographyCTCA at baseline and 2 years | Diagnostic test | Myocardial infarction |
| Cardiac MRICardiac MRI at 1 year | Diagnostic test | Myocardial infarction |
Primary outcome
68Ga-DOTATATE PET vs. plaque progression
Time frame: 2 years
Comparison of non-culprit coronary artery 68Ga-DOTATATE tissue-to-blood ratio at 12 weeks post-MI in patients with plaque progression (changes in low attenuation plaque volume and total atheroma volume) after 2 years measured by CTCA versus those without
5 secondary outcomes
68Ga-DOTATATE PET vs. CTCA-defined plaque morphology
Time frame: 2 years
68Ga-DOTATATE PET vs. intravascular imaging
Time frame: Baseline
68Ga-DOTATATE PET vs. hsCRP
Time frame: 2 years
68Ga-DOTATATE PET vs left ventricular myocardial function
Time frame: 1 year
68Ga-DOTATATE PET vs myocardial tissue characterization
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jul 2024.
- Background: PubMed 28385306Tarkin JM, Joshi FR, Evans NR, Chowdhury MM, Figg NL, Shah AV, Starks LT, Martin-Garrido A, Manavaki R, Yu E, Kuc RE, Grassi L, Kreuzhuber R, Kostadima MA, Frontini M, Kirkpatrick PJ, Coughlin PA, Gopalan D, Fryer TD, Buscombe JR, Groves AM, Ouwehand WH, Bennett MR, Warburton EA, Davenport AP, Rudd JH. Detection of Atherosclerotic Inflammation by 68Ga-DOTATATE PET Compared to [18F]FDG PET Imaging. J Am Coll Cardiol. 2017 Apr 11;69(14):1774-1791. doi: 10.1016/j.jacc.2017.01.060.
- Background: PubMed 25977567Pedersen SF, Sandholt BV, Keller SH, Hansen AE, Clemmensen AE, Sillesen H, Hojgaard L, Ripa RS, Kjaer A. 64Cu-DOTATATE PET/MRI for Detection of Activated Macrophages in Carotid Atherosclerotic Plaques: Studies in Patients Undergoing Endarterectomy. Arterioscler Thromb Vasc Biol. 2015 Jul;35(7):1696-703. doi: 10.1161/ATVBAHA.114.305067. Epub 2015 May 14.
- Background: PubMed 20080898Rominger A, Saam T, Vogl E, Ubleis C, la Fougere C, Forster S, Haug A, Cumming P, Reiser MF, Nikolaou K, Bartenstein P, Hacker M. In vivo imaging of macrophage activity in the coronary arteries using 68Ga-DOTATATE PET/CT: correlation with coronary calcium burden and risk factors. J Nucl Med. 2010 Feb;51(2):193-7. doi: 10.2967/jnumed.109.070672. Epub 2010 Jan 15.
- Derived from this study: PubMed 36697134Corovic A, Wall C, Nus M, Gopalan D, Huang Y, Imaz M, Zulcinski M, Peverelli M, Uryga A, Lambert J, Bressan D, Maughan RT, Pericleous C, Dubash S, Jordan N, Jayne DR, Hoole SP, Calvert PA, Dean AF, Rassl D, Barwick T, Iles M, Frontini M, Hannon G, Manavaki R, Fryer TD, Aloj L, Graves MJ, Gilbert FJ, Dweck MR, Newby DE, Fayad ZA, Reynolds G, Morgan AW, Aboagye EO, Davenport AP, Jorgensen HF, Mallat Z, Bennett MR, Peters JE, Rudd JHF, Mason JC, Tarkin JM. Somatostatin Receptor PET/MR Imaging of Inflammation in Patients With Large Vessel Vasculitis and Atherosclerosis. J Am Coll Cardiol. 2023 Jan 31;81(4):336-354. doi: 10.1016/j.jacc.2022.10.034.
- Individual participant dataSharing planned: No
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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.
Jason M Tarkin, MBBS PhD principal investigator
University of Cambridge
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Atherosclerosis and Myocardial Infarction, run by University of Cambridge at 1 site in United Kingdom.
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 11 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: status not confirmed, as of the sponsor's last update on 19 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. 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.
Are results available for this study?
Results are not available in the source record.
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?
68Ga-DOTATATE PET vs. plaque progression (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04073810, which also lists 4 linked publications.
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 19 Jul 2024.