Pharmacology Space Kit (PSK) - Dried Blood Spot for Caffeine Pharmacokinetics Under Microgravity Conditions

Drug Mechanism Clinical Trial

— PSK  

Official title:

Kit de Pharmacologie Spatial - Analyse de l'Utilisation Des Dried Blood Spot Pour le Dosage de la caféine Chez Des Volontaires Sains en microgravité au Cours Des Vols Paraboliques

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06431984
• Other study ID #: C22-80
• Secondary ID: 2022-A02794-39
• Status: Completed
• Phase: N/A
• Start date: March 27, 2023
• Est. completion date: April 3, 2024

Study information

• Verified date: May 2024
• Source: Institut National de la Santé Et de la Recherche Médicale, France
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The PSK study is preliminary to the study of drug metabolism in space flight conditions. The investigators propose to use simplified blood sampling methods that can be applied in microgravity. This method is based on the use of capillary blood, obtained using an automatic lancet for diabetics, the blood droplet then being deposited on specific blotting paper, and then studied in the laboratory. In 2022, the investigators validated the transfer of artificial blood in parabolic flight conditions, as well as the validity of cardiovascular drug dosage. The objective of the 2023 study is to validate the collection and transfer of capillary blood, on themselves, by healthy volunteers with little training, for the blood dosage of caffeine after intake of standard doses of alimentary caffeine. The primary objective is a feasibility of 90% of sampling in microgravity, compared with 95% on ground. Secondary objectives are the pharmacokinetic of different forms of caffeine, according to genetic background and other modifiers of CYP1A2.

Description:

The investigators propose to use simplified blood sampling methods that can be applied in microgravity. This method is based on the use of capillary blood, obtained using an automatic lancet for diabetics, the blood droplet then being deposited on specific blotting paper, and then studied in the laboratory. The objective of the study is to validate the collection and transfer of capillary blood from finger prick test, performed on themselves, by healthy volunteers after a short training, for the blood dosage of caffeine. Dietary caffeine will be used, issued from standardized espresso, tea or dark chocolate. Caffeine is a universally used food substance and is metabolised by a pathway common to many drugs (CYP 1A2). The aim is to show that it is possible to collect blood in this way, and to carry out assays of caffeine. Secondary objectives are to assess the kinetics of caffeine metabolism through the metabolic ratio (AUC paraxanthine/AUC caffeine), and to correlate these kinetics with genetic variations in CYP 1A2 activity. Participants are healthy volunteers already selected to take part in the parabolic flight campaign. A success rate of 95% for ground sampling, and 90% for in-flight sampling is assumed as satisfactory. If 5 volunteer participants during the 3 days of flying carry out 2 in-flight samplings, this results in 30 in-flight samplings. If the other 25 flying volunteers take only one in-flight sample, means 25 in-flight samples (total 55). On the ground, the 30 volunteers will take 90 samples, for a total of 145 minimum samples. An equivalence threshold for a maximum 20% difference between flight and ground conditions is considered. For a difference of 10, 15 and 20%, the power is 34, 79 and 97% respectively. It can therefore conclude that the difference between the two sampling conditions is not clinically significant.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: April 3, 2024
• Est. primary completion date: April 3, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Be affiliated to a social security scheme or benefit from such a scheme.
• Have obtained a medical certificate stating that they are fit for parabolic flights.
• Be aged between 18 and 70
• Be in good health: no chronic treatment that could interact with the metabolism of caffeine, no progressive disease
• Must not have any contraindications to taking caffeine (30 to 100 mg). Volunteers will also be asked not to consume caffeine (coffee, chocolate, energy drinks, tea, cola, etc.) in the 24 hours preceding the experiment.

Exclusion Criteria:

• Be the subject of a legal protection measure (safeguard of justice, curatorship or guardianship)
• suffer from haematophobia (irrational fear of blood)
• Have a current infectious disease, particularly viral
• Have an active chronic illness
• Have a high usual intake of caffeine (>4 espressos, >4 cups of tea, >100g dark chocolate per day)
• Total intolerance to all forms of caffeine
• Smoke more than 20 cigarettes a day
• Have weaned themselves off smoking for less than a month
• Have a history of severe Raynaud's phenomenon
• Have a history of naupathy
• Suffering from naupathy during a flight

Related Conditions & MeSH terms

• Drug Mechanism
• Metabolism Medication Toxicity
• Motion Sickness

Intervention

Diagnostic Test:
• prick test
self-sampling of capillary blood using the finger prick test method

Locations

Country	Name	City	State
France	AIRBUS A 310 - Zero-G	Mérignac

Sponsors (1)

Lead Sponsor	Collaborator
Institut National de la Santé Et de la Recherche Médicale, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of valid capillary blood deposit on dry support	A blood transfer is considered as successful IF the 3 following criteria are fulfilled; Blood spot covering > 8 mm2 (3 mm punch circle); Obtaining a drop of blood within the allotted time of 22 sec of microgravity; The drop is neither smeared nor smashed on the blotting paper	through study completion, an average of 3 days
Secondary	Identification of factors leading to self-sampling failure a. Time too short b. Insufficient drop c. Inadequate transfer	Identification of self-sampling failure factors; Deposition time in flight > 22 seconds of weightlessness; Blood stain covering 80% or more of the reference circle: diameter of the stain taken by photography	through study completion, an average of 1 year
Secondary	Caffeine kinetic under different formulations and dosages	Area under the curve of caffeine and paraxanthine, metabolic ratio (para/caffeine)	through study completion, an average of 3 days
Secondary	Caffeine kinetic under different CYP1A2 genotypes	Area under the curve of caffeine and paraxanthine, metabolic ratio (para/caffeine)	through study completion, an average of 3 days
Secondary	Caffeine kinetic under different gravity conditions	Area under the curve of caffeine and paraxanthine, metabolic ratio (para/caffeine)	through study completion, an average of 3 days
Secondary	Acceptability	A paper questionnaire will be handed out just after the parabolic flight at the time of the last sampling. It will be made up of closed questions based on 3 dimensions of satisfaction: The quality of the information given by the investigating team on the capillary blood sampling process in order to improve our paper-based operating procedure.; Their physical and psychological well-being during the finger prick test demonstration phase before the flight, during the flight and at the end of the flight campaign to ensure that the participants felt comfortable and confident in the sampling situation.; Assessment of their performance during the study in flight and on the ground, and whether they would be interested in self-sampling for a future space mission.	through study completion, an average of 1 year
Secondary	Stability of dry blood spots	Area under the curve of caffeine and paraxanthin, metabolic ratio (para/caffeine) at 6 months interval; Visual appearance (degradation, colour change, etc.); Comparison of relative areas obtained during the study with those obtained in a conventional laboratory situation	through study completion, an average of 1 year