Clinical trial NCT06398392: In Vivo Study of Neuroinflammation in Tobaccosmoking: a Clinical PET Study of TSPO Using [18F]PBR111
Official title: In Vivo Study of Neuroinflammation in Tobaccosmoking: a Clinical Positron EmissionTomography (PET) Study of 18 kDa TranslocatorProtein (TSPO) Using [18F]PBR111 (Part A)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Dosimetry
Healthy
Lead sponsor: University Hospital, Geneva
Sponsor class: OTHER
First posted: 2024-05-03
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: Tobacco smoking is associated with multiple and well-recognized adverse health effects. However, the direct effects of smoking on the brain are less well understood. On of the mechanisms that could be associated with tobacco-related brain toxicity is neuroinflammation. PET/CT imaging constitutes an excellent means of assessment of neuroinflammation in vivo, with the quantification of TSPO using \[18F\]PBR111. Nonetheless, this radiopharmaceutical has not been authorized for human use in Switzerland.

Detailed description: Our study thus includes two parts. Part A involves a dosimetry study (i.e. measure the exposure of the body organs of healthy individuals to radioactivity after the administration of 200 MBq of \[18F\]PBR111. This is a prerequisite for the authorization of the use of this radiotracer in humans. Next, the main part of this study (part B) involves the comparison of the quantity of TSPO in the brain of otherwise healthy smokers and age- and sex-matched non-smokers.

Part A:

Primary objective: to establish the exposure of the organs/tissues to a standard radioactive dose (200 MBq) of \[18F\]PBR111.

Eligibility criteria: Inclusion Criteria:

* Aged ≥18 (3 male and 3 female participants)
* Fluent in French and able and willing to provide written informed consent.

Exclusion Criteria:

* Homozygosity for the rs6971 polymorphism on TSPO that results in low-affinity binding. This criterion is added because this polymorphism alters significantly the ability of the radiotracer \[18F\]PBR111 to bind to TSPO, hence precluding quantification.
* Absence of a stable contraceptive regimen (specifically, intrauterine contraceptive device or contraceptive treatment per os). Only women with stable contraception will be added to eliminate the risk of exposure of pregnant women and their foetus to radioactivity.
* Presence of any significant history or current diagnosis of chronic disease or syndrome (including neurological, psychiatric, cardiovascular, oncological, metabolic, rheumatological conditions).
* One or more episode(s) of acute infectious or allergic reaction in the last month before inclusion and during the study period. Again, we cannot exclude that such conditions might produce immune alterations in the brain, thus confounding the results of TSPO quantification with \[18F\]PBR111.
* Presence of clinically relevant laboratory abnormalities in the haematological and biochemical blood tests, as defined as laboratory values that require clinical workup and/or treatment (e.g. anaemia, hyperglycaemia, electrolyte imbalances)
* A body mass index \<20 or \>30 (this criterion is necessary because TSPO has been shown to be variable with respect to body mass index (113-115)).
* Exposure to research related radiation in the past five years that, when combined with this study, would place subjects above the allowable limits.
* Conditions precluding entry into the scanners (e.g. claustrophobia).

Primary outcomes:
measure: Measurement of radiation dosimetry and biodistribution of the translocator protein radiotracer [18F]PBR111 determined with PET/CT in healthy human volunteers (3 male and 3 female participants)
timeFrame: 6 months
Secondary outcomes:
measure: Calculation of the total radiation exposure of a PET/CT with 200 MBq of [18F]PBR111
timeFrame: 6 months
Other outcomes:
Locations:
Study officials:
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