Residual Inflammation and Plaque Progression Long-term Evaluation

Coronary Artery Disease Clinical Trial

— RIPPLE  

Official title:

Residual Inflammation and Plaque Progression Long-term Evaluation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04073810
• Other study ID #: A095007 (RIPPLE)
• Status: Recruiting
• Start date: October 1, 2020
• Est. completion date: October 1, 2023

Study information

• Verified date: March 2022
• Source: University of Cambridge
• Contact: Jason M Tarkin, MBBS PhD
• Phone: +44(0)1223331504
• Email: jt545[@]cam.ac.uk
• Is FDA regulated: No
• Study type: Observational

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: October 1, 2023
• Est. primary completion date: October 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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

Related Conditions & MeSH terms

• Atherosclerosis
• Coronary Artery Disease
• Infarction
• Inflammation
• Myocardial Infarction

Intervention

Diagnostic Test:
• PET imaging
Coronary 68Ga-DOTATATE PET-MRI or PET-CT at baseline and 3 months
• Coronary CT angiography
CTCA at baseline and 2 years
• Cardiac MRI
Cardiac MRI at 1 year

Locations

Country	Name	City	State
United Kingdom	University of Cambridge	Cambridge

Sponsors (3)

Lead Sponsor	Collaborator
University of Cambridge	Cambridge University Hospitals NHS Foundation Trust, Wellcome Trust

Country where clinical trial is conducted

United Kingdom, 

References & Publications (3)

Pedersen SF, Sandholt BV, Keller SH, Hansen AE, Clemmensen AE, Sillesen H, Højgaard L, Ripa RS, Kjær 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. — View Citation

Rominger A, Saam T, Vogl E, Ubleis C, la Fougère C, Förster 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. — View Citation

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 (68)Ga-DOTATATE PET Compared to [(18)F]FDG PET Imaging. J Am Coll Cardiol. 2017 Apr 11;69(14):1774-1791. doi: 10.1016/j.jacc.2017.01.060. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	2 years
Secondary	68Ga-DOTATATE PET vs. CTCA-defined plaque morphology	Comparison of coronary 68Ga-DOTATATE imaging to changes in plaque morphology measured by CTCA	2 years
Secondary	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	Baseline
Secondary	68Ga-DOTATATE PET vs. hsCRP	Comparison of 68Ga-DOTATATE PET to high-sensitivity C-reactive protein	2 years
Secondary	68Ga-DOTATATE PET vs left ventricular myocardial function	Comparison of myocardial 68Ga-DOTATATE PET to left ventricular size and function	1 year
Secondary	68Ga-DOTATATE PET vs myocardial tissue characterization	Comparison of myocardial 68Ga-DOTATATE PET to myocardial scarring and oedema	1 year