Early Feasibility Study of Somatostatin Receptors PET Imaging for the Diagnosis of Infective Endocarditis (DOTENDO)

Early Feasibility Study of Somatostatin Receptors PET Imaging (68Ga-DOTATOC PET/CT) for the Diagnosis of Infective Endocarditis

Study hypothesis: 68Ga-DOTATOC PET/CT could detect cardiac foci of infective endocarditis regardless of the type of valve (native or prosthetic) and also extracardiac localizations related to this pathology (infection responsible, peripheral emboli, ...). This study is a proof of concept with low population

Study Overview

• Status: Not yet recruiting
• Conditions: Infective Endocarditis
• Intervention / Treatment: Drug: 68Ga-DOTATOC PET/CT

Detailed Description

The incidence of infective endocarditis (IE) in France is estimated to be around 30 cases per million inhabitants in studies conducted in Western countries and is significantly increased in patients with a valve prosthesis and even more so in cases of a history of endocarditis. The morbi-mortality is significant and the hospital mortality rate is 20%.

The diagnosis of IE remains difficult and according to the modified Duke criteria, the diagnostic sensitivity is 80%.

Currently, the diagnosis of IE is often determined according to the 2015 ESC criteria and the sensitivity increases from 57% to 84% regarding IE on prosthetic valves.

The 18F-FDG PET/CT examination is of major interest in the diagnosis of AR on prosthetic valves with a detection sensitivity of between 70 and 90% (with an accuracy of 70 to 80%). Concerning native valves, the sensitivity of PET/CT remains below 50%.

Indeed, a "physiological" myocardial fixation in 18F-FDG PET/CT compromises the interpretation of PET exam, so it is important to start a hypoglucidic-hyperlipidic diet the day before the 18F-FDG PET/CT, followed by a 12-hour fasting period.

For several years, a radiopharmaceutical, 68Ga-DOTATOC (68Ga-edotreotide) has been used in PET/CT for the diagnosis and follow-up of neuroendocrine tumours (NETs). 68Ga-DOTATOC binds mainly with high affinity to somatostatin receptor subtype 2 (SSTR2) but also to somatostatin receptor subtype 5 (SSTR5).

Activated monocytes, macrophages, and lymphocytes express somatostatin receptors , thus detection of SSTR2 receptors expressed by inflammatory cells could help for the diagnosis of infective endocarditis.

PET/CT with 68Ga-DOTATOC could thus detect inflammatory cells at infectious sites. This radiopharmaceutical has already shown an ability to identify a myocardial inflammation (inflammatory phase myocarditis and cardiac sarcoidosis).

In current study conducted by our teams (NCT03347760 on ClinicalTrials.gov), early results showed the capacity of the 68Ga-DOTATOC to detect efficiently myocarditis, including myocarditis induced by RNA anti-COVID vaccinations.

In vitro, the 18FDG uptake by inflammatory cells is more important than the 68Ga-DOTATOC uptake, but the contrast between infection focus and healthy tissue should be better since 68Ga-DOTATOC does not cause any physiological myocardial uptake. The 68Ga-DOTATOC does not required any special metabolic preparation or prolonged fasting often poorly supported by patients.

• Study Type: Interventional
• Enrollment (Anticipated): 14
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: VERONIQUE ROCH, MSc; Phone Number: +33 383154276; Email: v.roch@chru-nancy.fr
• Study Contact Backup: Name: Caroline BOURSIER, MD; Phone Number: +33 383154039; Email: c.boursier@chru-nancy.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult who has received full information about the organisation of the research and has signed informed consent adult
• Participant hospitalised for definite AE according to modified Duke criteria (Li), on native or prosthetic valve, referred for 18F-FDG PET/CT from Cardiology and Infectious Diseases departments

Exclusion Criteria:

• Person with a history of hypersensitivity from previous use of 68Ga-DOTATOC
• Unable to perform a 68Ga-DOTATOC PET scan (agitated, confused patient...).
• Inability to schedule 68Ga-DOTATOC PET/CT the day after 18F-FDG PET/CT.
• Person with severe renal impairment (GFR <30 ml/min/1.73 m2)
• Participant treated with a somatostatin analogue.
• Participant with Cushing's syndrome
• Pregnant, potentially pregnant or breastfeeding women
• Adult subject to a legal protection measure (guardianship, curatorship, safeguard of justice)
• Person of full age who is unable to give consent
• Person deprived of liberty by a judicial or administrative decision
• Person subject to psychiatric care by virtue of Articles L. 3212-1 and L. 3213-1

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: Patients with definite IE will be included and referred for 18F-FDG PET/CT in the study; Fourteen patients with definite IE according to the modified Duke criteria (Li) will be included and referred for 18F-FDG PET/CT in the study. A 68Ga-DOTATOC PET/CT scan will be performed specifically for research at 24 hours.	Drug: 68Ga-DOTATOC PET/CT; 68Ga-DOTATOC PET/CT will be recorded the following day of 18F-FDG PET/CT if patient signed the consent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Detectability of infective endocarditis by 68Ga-DOTATOC PET/CT	to visually evaluate the detectability of cardiac and extracardiac foci associated with infective endocarditis (IE) on native or prosthetic valve by 68Ga-DOTATOC PET/CT.	one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To quantify the infective foci uptake of 68Ga-DOTATOC	To quantify the infective foci uptake of 68Ga-DOTATOC with measure of Standard Uptake Value (SUV) related to blood activity.	one year
68Ga-DOTATOC PET/CT and 18F-FDG PET/CT results comparison	To compare 68Ga-DOTATOC PET/CT results with 18F-FDG PET/CT results, of visual and quantitative analysis on whole body PET/CT	one year
68Ga-DOTATOC PET/CT and 18F-FDG PET/CT results comparison of cardiac step	3. To compare the 68Ga-DOTATOC PET/CT results with those of 18F-FDG PET/CT, of visual and quantitative analysis of cardiac step recordings	one year

Collaborators and Investigators

• Sponsor: Central Hospital, Nancy, France

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2022
• Primary Completion (Anticipated): March 1, 2023
• Study Completion (Anticipated): January 1, 2024

Study Registration Dates

• First Submitted: December 21, 2021
• First Submitted That Met QC Criteria: December 21, 2021
• First Posted (Actual): January 10, 2022

Study Record Updates

• Last Update Posted (Actual): January 10, 2022
• Last Update Submitted That Met QC Criteria: December 21, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Infections; Bacterial Infections; Bacterial Infections and Mycoses; Cardiovascular Infections; Endocarditis, Bacterial; Endocarditis; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Edotreotide
• Other Study ID Numbers: 2021PI119

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