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PET Imaging of Inflammation and Lipid Lowering Study (PIILL)

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ClinicalTrials.gov Identifier: NCT04073797
Recruitment Status : Not yet recruiting
First Posted : August 29, 2019
Last Update Posted : August 30, 2019
Sponsor:
Collaborators:
Cambridge University Hospitals NHS Foundation Trust
Wellcome Trust
Information provided by (Responsible Party):
Jason Tarkin, University of Cambridge

Brief 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. 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.

Condition or disease Intervention/treatment Phase
Hypercholesterolemia Hypercholesterolemia, Familial Drug: PCSK9 inhibitor Diagnostic Test: 68Ga-DOTATATE PET-MRI Not Applicable

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 stable cardiovascular disease or heterozygous familial hypercholesterolemia (HeFH) and elevated low density lipoprotein (LDL) cholesterol despite high-intensity statin treatment will undergo serial carotid 68Ga-DOTATATE PET-magnetic resonance imaging (MRI) in a double-blind, two-arm, parallel-design, placebo-controlled study.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 56 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Double-blind, placebo controlled.
Primary Purpose: Diagnostic
Official Title: PET Imaging of Inflammation and Lipid Lowering Study
Estimated Study Start Date : October 1, 2019
Estimated Primary Completion Date : October 1, 2023
Estimated Study Completion Date : October 1, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Stable CVD - treatment
Stable CVD with elevated LDL cholesterol despite high-intensity atorvastatin, randomised to add on therapy with a PCSK9 inhibitor
Drug: PCSK9 inhibitor
PCSK9 inhibitor
Other Names:
  • Alirocumab
  • Evolocumab

Diagnostic Test: 68Ga-DOTATATE PET-MRI
68Ga-DOTATATE PET-MRI at baseline and 12 weeks

Placebo Comparator: Stable CVD - placebo control
Stable CVD with elevated LDL cholesterol despite high-intensity atorvastatin, randomised to placebo control
Diagnostic Test: 68Ga-DOTATATE PET-MRI
68Ga-DOTATATE PET-MRI at baseline and 12 weeks

Experimental: HeFH - treatment
HeFH and elevated LDL cholesterol despite high-intensity atorvastatin, randomised to add on therapy with a PCSK9 inhibitor
Drug: PCSK9 inhibitor
PCSK9 inhibitor
Other Names:
  • Alirocumab
  • Evolocumab

Diagnostic Test: 68Ga-DOTATATE PET-MRI
68Ga-DOTATATE PET-MRI at baseline and 12 weeks

Placebo Comparator: HeFH - placebo control
HeFH and elevated LDL cholesterol despite high-intensity atorvastatin, randomised to placebo control
Diagnostic Test: 68Ga-DOTATATE PET-MRI
68Ga-DOTATATE PET-MRI at baseline and 12 weeks




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. Carotid 68Ga-DOTATATE vs. MRI [ Time Frame: 12 weeks ]
    Comparison of carotid artery 68Ga-DOTATATE imaging to changes in plaque morphology assessed by high-resolution carotid MRI

  2. Carotid 68Ga-DOTATATE vs. serum lipids [ Time Frame: 12 weeks ]
    Comparison of carotid 68Ga-DOTATATE imaging to serum lipids

  3. Carotid 68Ga-DOTATATE vs. hsCRP [ Time Frame: 12 weeks ]
    Comparison of carotid 68Ga-DOTATATE imaging to high-sensitivity C-reactive protein (hsCRP)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female participants >18 years old
  • Able to give written, informed consent and to lie flat
  • Have a history of CVD (acute coronary syndrome, ischaemic stroke, transient ischaemic attack, or documented coronary, carotid, or peripheral arterial disease) and elevated LDL cholesterol despite high-intensity atorvastatin (Group 1), or
  • Have HeFH (definite or probable FH based on clinical criteria) and elevated LDL cholesterol despite high-intensity atorvastatin (Group 2)
  • Lipid lowering therapy unchanged for at least 6 weeks prior to screening

Exclusion Criteria:

  • Women of child bearing potential not using adequate contraception
  • Contra-indication to MRI scanning
  • Statin-associated myositis or liver function abnormality
  • Sensitivity to PCSK9 inhibitors or monoclonal antibodies
  • Contrast allergy or contrast-nephropathy
  • 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 medication
  • Current use of systemic corticosteroids
  • Previous carotid endarterectomy surgery or stenting

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04073797


Contacts
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Contact: Jason M Tarkin, MBBS PhD +44(0)1223331504 jt545@cam.ac.uk

Locations
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United Kingdom
University of Cambridge Not yet recruiting
Cambridge, United Kingdom
Contact: Jason M Tarkin, MBBS PhD    +44(0)1223331504    jt545@cam.ac.uk   
Sub-Investigator: James HF Rudd, MD PhD         
Sponsors and Collaborators
University of Cambridge
Cambridge University Hospitals NHS Foundation Trust
Wellcome Trust
Investigators
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Principal Investigator: Jason M Tarkin, MBBS PhD University of Cambridge

Publications:
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Responsible Party: Jason Tarkin, Wellcome Clinical Research Career Development Fellow & Clinical Lecturer, University of Cambridge
ClinicalTrials.gov Identifier: NCT04073797     History of Changes
Other Study ID Numbers: A095007 (PIILL)
First Posted: August 29, 2019    Key Record Dates
Last Update Posted: August 30, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Hypercholesterolemia
Hyperlipoproteinemia Type II
Inflammation
Pathologic Processes
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Hyperlipoproteinemias
Evolocumab
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents