Residual Inflammation and Plaque Progression Long-term Evaluation

NCT ID: NCT04073810

Last Updated: 2024-07-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Total Enrollment

40 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-10-01

Study Completion Date

2025-04-01

Brief Summary

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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

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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.

Conditions

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Atherosclerosis Myocardial Infarction Coronary Artery Disease Inflammation

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Myocardial infarction

Patients with recent MI

PET imaging

Intervention Type DIAGNOSTIC_TEST

Coronary 68Ga-DOTATATE PET-MRI or PET-CT at baseline and 3 months

Coronary CT angiography

Intervention Type DIAGNOSTIC_TEST

CTCA at baseline and 2 years

Cardiac MRI

Intervention Type DIAGNOSTIC_TEST

Cardiac MRI at 1 year

Interventions

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PET imaging

Coronary 68Ga-DOTATATE PET-MRI or PET-CT at baseline and 3 months

Intervention Type DIAGNOSTIC_TEST

Coronary CT angiography

CTCA at baseline and 2 years

Intervention Type DIAGNOSTIC_TEST

Cardiac MRI

Cardiac MRI at 1 year

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

99 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Cambridge University Hospitals NHS Foundation Trust

OTHER

Sponsor Role collaborator

Wellcome Trust

OTHER

Sponsor Role collaborator

University of Cambridge

OTHER

Sponsor Role lead

Responsible Party

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Jason Tarkin

Wellcome Clinical Research Career Development Fellow & Clinical Lecturer

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Jason M Tarkin, MBBS PhD

Role: PRINCIPAL_INVESTIGATOR

University of Cambridge

Locations

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University of Cambridge

Cambridge, , United Kingdom

Site Status

Countries

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United Kingdom

References

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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.

Reference Type BACKGROUND
PMID: 28385306 (View on PubMed)

Pedersen 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.

Reference Type BACKGROUND
PMID: 25977567 (View on PubMed)

Rominger 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.

Reference Type BACKGROUND
PMID: 20080898 (View on PubMed)

Corovic 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.

Reference Type DERIVED
PMID: 36697134 (View on PubMed)

Other Identifiers

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A095007 (RIPPLE)

Identifier Type: -

Identifier Source: org_study_id

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