HypercholesterolemiaPIILLNCT04073797
PET Imaging of Inflammation and Lipid Lowering Study
A study testing Inclisiran, 68Ga-DOTATATE PET-MRI and Colchicine in people with Hypercholesterolemia and Hypercholesterolemia, Familial, run by University of Cambridge at 1 site in United Kingdom.
Trial summary
While 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging has been used as an early marker of drug efficacy in numerous clinical cardiovascular drug trials, as a glucose analog, its signal in the vasculature lacks inflammatory cell-specificity. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Hypercholesterolemia, Hypercholesterolemia, Familial, Atherosclerosis
- What is being tested?
- Inclisiran, 68Ga-DOTATATE PET-MRI and Colchicine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 20 Mar 2023to 30 May 2026
- Phase
- Interventional
- 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
Who may be able to join
- Male or female participants >18 years old
- Able to give written, informed consent and to lie flat
- Have primary hypercholesterolaemia (non-familial or definite or possible heterozygous familial hypercholesterolaemia (HeFH) based on clinical criteria) or mixed dyslipidaemia, and
- History of CVD (acute coronary syndrome, coronary or other revascularisation procedures, coronary heart disease, ischaemic stroke, or peripheral arterial disease) and elevated LDL cholesterol ≥2.6 despite maximum tolerated statins with or without other lipid lowering therapies (see NICE TA 733), and
- Lipid lowering therapy unchanged for at least 6 weeks prior to screening, and
- Pre-existing carotid atherosclerotic plaque ≥15mm by B-mode ultrasound
Who cannot join
- Women of childbearing potential not using adequate contraception
- Contra-indication to MRI scanning
- Statin-associated myositis or liver function abnormality
- Already taking inclisiran or colchicine
- Sensitivity and/or contraindication to inclisiran or colchicine. Contraindications to colchicine include severe hepatic or renal impairment, blood disorders, and patients with renal or hepatic impairment who are taking a P-gp inhibitor or a strong CYP3A4 inhibitor
- Contrast allergy or contrast-nephropathy
Show all 14Show fewer
- Chronic kidney disease (eGFR <30 mL/min/1.73 m2)
- Cardiovascular event within 6 months
- 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
- Treatment with medications that result in significant drug to drug interactions with the study medications
- Current use of systemic corticosteroids or other immunosuppressive drugs
- Previous or planned carotid endarterectomy surgery or stenting on the index side
Trial locations and contacts
1 site in 1 country.
About this study
While 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging has been used as an early marker of drug efficacy in numerous clinical cardiovascular drug trials, as a glucose analog, its signal in the vasculature lacks inflammatory cell-specificity. Moreover, high background 18F-FDG signals from the myocardium often preclude coronary artery imaging, despite attempts to suppress myocardial tracer uptake by dietary manipulation. These limitations of 18F-FDG for measuring changes in vascular inflammation arising from drug intervention highlight important unmet needs, which might be overcome by using a somatostatin receptor subtype-2 (SST2) PET tracer.
Read the detailed description
Up-regulation of SST2 in activated macrophages represents a novel imaging target for measuring vascular inflammation, which has been previously examined in atherosclerosis using 68Ga-DOTATATE. To test the hypothesis that 68Ga-DOTATATE can quantify drug-induced changes in arterial inflammation, patients with primary hypercholesterolaemia (non-familial or familial) or mixed dyslipidaemia with stable cardiovascular Disease (CVD) and elevated LDL cholesterol ≥2.6 despite maximum tolerated statins with or without other lipid lowering therapies will undergo carotid artery 68Ga-DOTATATE PET-magnetic resonance imaging (MRI) in a randomised, double-blind, placebo-controlled study of inclisiran or colchicine.
In parallel, we will examine a novel method for detecting plaque composition based on analysis of ultrasound centre frequency shifts, which was developed by collaborators in Lund University, Sweden. The Ultrasound Plaque Structure Analysis (UPSA) method uses radiofrequency algorithms to create real-time tissue-like maps of carotid plaques. Participants in the study will undergo carotid ultrasound imaging using the UPSA method in addition to PET/MRI.
- Conditions
- Hypercholesterolemia, Hypercholesterolemia, Familial, Atherosclerosis, Carotid Artery Plaque
- Being tested
- Inclisiran, 68Ga-DOTATATE PET-MRI, Colchicine
- Medical subject headings
- Hypercholesterolemia, Hyperlipoproteinemia Type II, Atherosclerosis, Carotid Stenosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
InclisiranDrug
Inclisiran 284 mg, one injection
68Ga-DOTATATE PET-MRIDiagnostic test
68Ga-DOTATATE PET-MRI at baseline and 12 weeks
ColchicineDrug
Colchicine 500 mcg tablet once daily
| Study group | Role | What they receive |
|---|---|---|
| Stable CVD - treatment | Experimental | Stable CVD with LDL ≥2.6 despite maximally tolerated statins ± other lipid lowering therapies, randomised to add on therapy with inclisiran + placebo tablet Receives: Drug: Inclisiran; Diagnostic Test: 68Ga-DOTATATE PET-MRI |
| Stable CVD - placebo control | Active comparator | Stable CVD with LDL ≥2.6 despite maximally tolerated statins ± other lipid lowering therapies, randomised to placebo injection + colchicine tablet Receives: Diagnostic Test: 68Ga-DOTATATE PET-MRI; Drug: Colchicine |
| HeFH - treatment | Placebo comparator | Stable CVD with LDL ≥2.6 despite maximally tolerated statins ± other lipid lowering therapies, randomised to placebo injection + placebo tablet Receives: Drug: Inclisiran; Diagnostic Test: 68Ga-DOTATATE PET-MRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Carotid 68Ga-DOTATATE PET
Relative change from baseline in carotid artery 68Ga-DOTATATE tissue-to-blood ratio in the index vessel
Measured: 12 weeks
Carotid UPSA imaging
Relative change from baseline in carotid artery UPSA signal in the index vessel
Measured: 12 weeks
Secondary outcomes (3)
MRI plaque burden
Relative change from baseline in carotid artery total plaque burden and lipid-rich necrotic core measured by MRI
Measured: 12 weeks
Carotid 68Ga-DOTATATE vs. serum lipids
Comparison of carotid 68Ga-DOTATATE imaging to serum lipids
Measured: 12 weeks
Carotid 68Ga-DOTATATE vs. hsCRP
Comparison of carotid 68Ga-DOTATATE imaging to high-sensitivity C-reactive protein (hsCRP)
Measured: 12 weeks
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 start20 Mar 2023
- Primary completion30 May 2026
- Study completion30 May 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HypercholesterolemiaStudies 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 N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Cambridge
- Sponsor type
- University, hospital or other
- Collaborators
- Cambridge University Hospitals NHS Foundation Trust, Wellcome Trust, GE Healthcare, Lund University, British Heart Foundation
- 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
- NCT04073797
- Sponsor's protocol ID
- A095007 (PIILL)
- Acronym
- PIILL
- Status last verified
- Oct 2026
- First submitted
- 27 Aug 2019
- Last updated
- 29 Oct 2026
- 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 25977567
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PET Imaging of Inflammation and Lipid Lowering Study
- ClinicalTrials.gov ID
- NCT04073797
- Acronym / sponsor ID
- PIILL / A095007 (PIILL)
- Conditions
- Hypercholesterolemia, Hypercholesterolemia, Familial, Atherosclerosis, Carotid Artery Plaque
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- University of CambridgeUniversity, hospital or other
- Collaborators
- Cambridge University Hospitals NHS Foundation Trust, Wellcome Trust, GE Healthcare, Lund University, British Heart Foundation
- Study start
- 20 Mar 2023 (actual)
- Primary completion
- 30 May 2026 (actual)
- Study completion
- 30 May 2026 (actual)
- 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.
While 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging has been used as an early marker of drug efficacy in numerous clinical cardiovascular drug trials, as a glucose analog, its signal in the vasculature lacks inflammatory cell-specificity. Moreover, high background 18F-FDG signals from the myocardium often preclude coronary artery imaging, despite attempts to suppress myocardial tracer uptake by dietary manipulation. These limitations of 18F-FDG for measuring changes in vascular inflammation arising from drug intervention highlight important unmet needs, which might be overcome by using a somatostatin receptor subtype-2 (SST2) PET tracer.
Detailed description
Up-regulation of SST2 in activated macrophages represents a novel imaging target for measuring vascular inflammation, which has been previously examined in atherosclerosis using 68Ga-DOTATATE. To test the hypothesis that 68Ga-DOTATATE can quantify drug-induced changes in arterial inflammation, patients with primary hypercholesterolaemia (non-familial or familial) or mixed dyslipidaemia with stable cardiovascular Disease (CVD) and elevated LDL cholesterol ≥2.6 despite maximum tolerated statins with or without other lipid lowering therapies will undergo carotid artery 68Ga-DOTATATE PET-magnetic resonance imaging (MRI) in a randomised, double-blind, placebo-controlled study of inclisiran or colchicine.
In parallel, we will examine a novel method for detecting plaque composition based on analysis of ultrasound centre frequency shifts, which was developed by collaborators in Lund University, Sweden. The Ultrasound Plaque Structure Analysis (UPSA) method uses radiofrequency algorithms to create real-time tissue-like maps of carotid plaques. Participants in the study will undergo carotid ultrasound imaging using the UPSA method in addition to PET/MRI.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Stable CVD - treatment | Experimental | Drug: Inclisiran, Diagnostic Test: 68Ga-DOTATATE PET-MRIStable CVD with LDL ≥2.6 despite maximally tolerated statins ± other lipid lowering therapies, randomised to add on therapy with inclisiran + placebo tablet |
| Stable CVD - placebo control | Active comparator | Diagnostic Test: 68Ga-DOTATATE PET-MRI, Drug: ColchicineStable CVD with LDL ≥2.6 despite maximally tolerated statins ± other lipid lowering therapies, randomised to placebo injection + colchicine tablet |
| HeFH - treatment | Placebo comparator | Drug: Inclisiran, Diagnostic Test: 68Ga-DOTATATE PET-MRIStable CVD with LDL ≥2.6 despite maximally tolerated statins ± other lipid lowering therapies, randomised to placebo injection + placebo tablet |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Male or female participants >18 years old
- Able to give written, informed consent and to lie flat
- Have primary hypercholesterolaemia (non-familial or definite or possible heterozygous familial hypercholesterolaemia (HeFH) based on clinical criteria) or mixed dyslipidaemia, and
- History of CVD (acute coronary syndrome, coronary or other revascularisation procedures, coronary heart disease, ischaemic stroke, or peripheral arterial disease) and elevated LDL cholesterol ≥2.6 despite maximum tolerated statins with or without other lipid lowering therapies (see NICE TA 733), and
- Lipid lowering therapy unchanged for at least 6 weeks prior to screening, and
Key exclusion criteria (14 listed)
- Women of childbearing potential not using adequate contraception
- Contra-indication to MRI scanning
- Statin-associated myositis or liver function abnormality
- Already taking inclisiran or colchicine
- Sensitivity and/or contraindication to inclisiran or colchicine. Contraindications to colchicine include severe hepatic or renal impairment, blood disorders, and patients with renal or hepatic impairment who are taking a P-gp inhibitor or a strong CYP3A4 inhibitor
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 |
|---|---|---|
| InclisiranInclisiran 284 mg, one injection | Drug | HeFH - treatment, Stable CVD - treatment |
| 68Ga-DOTATATE PET-MRI68Ga-DOTATATE PET-MRI at baseline and 12 weeks | Diagnostic test | HeFH - treatment, Stable CVD - placebo control, Stable CVD - treatment |
| ColchicineColchicine 500 mcg tablet once daily | Drug | Stable CVD - placebo control |
Primary outcome
Carotid 68Ga-DOTATATE PET
Time frame: 12 weeks
Relative change from baseline in carotid artery 68Ga-DOTATATE tissue-to-blood ratio in the index vessel
Carotid UPSA imaging
Time frame: 12 weeks
Relative change from baseline in carotid artery UPSA signal in the index vessel
3 secondary outcomes
MRI plaque burden
Time frame: 12 weeks
Carotid 68Ga-DOTATATE vs. serum lipids
Time frame: 12 weeks
Carotid 68Ga-DOTATATE vs. hsCRP
Time frame: 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Oct 2026.
- 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.
- 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?
A study testing Inclisiran, 68Ga-DOTATATE PET-MRI and Colchicine in people with Hypercholesterolemia and Hypercholesterolemia, Familial, 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 6 inclusion and 14 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: finished, as of the sponsor's last update on 29 Oct 2026. 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. Some participants in this study may receive a placebo. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Carotid 68Ga-DOTATATE PET (time frame: 12 weeks). The study lists 2 primary outcomes in all. 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 NCT04073797, which also lists 2 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 29 Oct 2026; AzTrials last refreshed its copy on 6 Nov 2026.