The Effect of Statin Treatment on Arterial Wall Inflammation as Assessed With 68Ga-DOTATATE PET-CT (CARAMEL)

The Effect of Statin Treatment on Arterial Wall Inflammation in Patients With Diabetes Mellitus as Assessed With 68Ga-DOTATATE PET-CT

To study the effect of atorvastatin treatment on vascular uptake of 68Ga-DOTATATE in patients with Type 2 Diabetes.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2; Vascular Inflammation
• Intervention / Treatment: Drug: Atorvastatin 40 Mg Oral Tablet

Detailed Description

Well controlled patients with type 2 diabetes, who are statin naïve, will undergo atorvastatin treatment. Before and after treatment, patients will undergo a 68Ga-DOTATATE PET/CT, to evaluate the effect of treatment on vascular inflammation.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1105AZ
      • Amsterdam UMC, location AMC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Aged 50 years and older
2. Diagnosed with diabetes mellitus type 2 and using oral glucose lowering therapy, insulin or combined glucose lowering therapy.
3. Not on statin therapy or willing to stop with current statin therapy for 6 weeks prior to visit 2.
4. HbA1c values below 65 mmol/L.
5. Patients with "stable" diabetes mellitus, i.e. no changes in type of glucose lowering therapy and / or dosage of oral glucose lowering therapy in the past three months. No more than 20% change in dosage of insulin therapy (short and long acting) in the last three months.

Exclusion Criteria:

1. History of cardiovascular disease (previous CV-event (MI / stroke) or known coronary artery disease (including acute coronary syndrome).
2. History of chronic kidney disease stage 3b - 5, defined as a CKD-EPI value of < 45 ml/min/1,73m2
3. Malignant diseases or any clinically significant medical condition that could interfere with the conduct of the study in the opinion of the investigator.
4. Chronic or recent (< 1 month) infections and/or clinical signs of acute infection.
5. History of auto-immune diseases.
6. Standard contra-indications to 68Ga-Dotatate PET, and CT based on physicians experience and current practices.
7. Inability or unwillingness to comply with the protocol requirements, or deemed by investigator to be unfit for the study.
8. Planned radiation exposure in the next year due to participation in a research project with radiation exposure or for clinical reasons.
9. Elevated liver enzymes (> 2 ULN of liver transaminases), acute liver failure or known liver disease.

10. Prior medium to severe statin-related side effects or statin related hypersensitivity, i.e.

    (severe) muscle pains with and/or without myopathy .

11. The concomitant use of statin contra-indicated drugs, including the use of CYP3A4 inhibitors (i.e. erytromycin, dilthiazem, amiodaron, verapamil, fluconazole, ciclosporin, stiripentol, itraconazol, ketoconazol, voriconazol, posaconazol, clarithromycin, ..), systemic use of fusidic acid and ciclosporin.
12. Any contra-indications to the use of statins.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention arm; Atorvastatin 40mg once daily.	Drug: Atorvastatin 40 Mg Oral Tablet; Atorvastatin 40mg once daily for three months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DOTATATE coronary arteries	Change in DOTATATE TBRmax coronary arteries after atorvastatin therapy	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in splenic/bone marrow DOTATATE signal	The secondary objective of this study is to assess the feasibility to measure splenic and bone-marrow inflammatory activity with 68Ga-Dotatate PET-CT in patients with diabetes mellitus, expressed as SUVmax	3 month

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2019
• Primary Completion (Actual): May 6, 2022
• Study Completion (Actual): May 6, 2022

Study Registration Dates

• First Submitted: February 7, 2023
• First Submitted That Met QC Criteria: February 7, 2023
• First Posted (Actual): February 16, 2023

Study Record Updates

• Last Update Posted (Actual): February 16, 2023
• Last Update Submitted That Met QC Criteria: February 7, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: type 2 diabetes mellitus; vascular inflammation; statin; pet/ct; dotatate; positron emmission tomography
• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Inflammation; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin
• Other Study ID Numbers: NL65001.018.18

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No