Feasibility and Validation of the Fluispotter®, a Novel Intravenous System for Serial Blood Sampling (FLUISPOTTER)

The purpose of this study is to test the Fluispotter® technology: A novel system for collection of serial venous samples, which may overcome some of the problems associated with repeated sampling or 20-hour collection of blood samples using standard procedures. The Fluispotter® is the first fully automated, wearable device for obtaining serial blood samples from humans. It is designed to function without operator intervention. The wearable device and - when in place - painless sampling allow sampling during different situations e.g., during sleep, work, play or exercise - whatever the sampling situation requires, including sampling not possible today using wet samples e.g. during everyday activities. Further, it reduces the number of man-hours needed for serial sampling, and minimizes the risks of sample loss, wrong timing, misidentification and contamination.

The primary purpose of this investigator-initiated study is to assess the feasibility, including benefits and harms, of the Fluispotter®, a novel method for serial blood sampling, versus standard blood sampling. The planned setting is a test of the Fluispotter® is a 20-hour period in healthy adults and in adults with secondary adrenal insufficiency due to pituitary disease.

Study Overview

• Status: Not yet recruiting
• Conditions: Adrenal Insufficiency
• Intervention / Treatment: Device: Fluispotter®

Detailed Description

Background In an every-day endocrine setting the dynamic response of hormones is assessed for the diagnosis and evaluation of several conditions such as adrenal insufficiency, Cushing's disease, acromegaly, and growth hormone insufficiency. These procedures require repeated venous sampling. A novel system for collection of serial samples, the Fluispotter®, may overcome some of these problems associated with repeated sampling or 20-hour collection of blood samples. The Fluispotter® is the first fully automated, wearable device for obtaining serial blood samples from humans. It is designed to function without operator intervention. The wearable device and - when in place - painless sampling allow sampling during different situations e.g., during sleep, work, play or exercise - whatever the sampling situation requires, including sampling not possible today using wet samples e.g. during everyday activities. Further, it reduces the number of man-hours needed for serial sampling, and minimizes the risks of sample loss, wrong timing, misidentification and contamination. The dried blood spot technology used in the Fluispotter® was tested for cortisol by comparing with plasma samples and the interassay accuracy and precision were reported to less than 10% across a range of different haematocrit values.

Aim The primary purpose of this investigator-initiated study is to assess the feasibility, including benefits and harms, of the Fluispotter®, a novel method for serial blood sampling, versus standard blood sampling. The planned setting is a test of the Fluispotter® is a 20-hour period in healthy adults and in adults with secondary adrenal insufficiency due to pituitary disease.

The primary outcome for this study is feasibility. This will be assessed using a standardized questionnaire for both staff and participants including items regarding duration of the insertion procedure, ease of insertion, number of re-insertions during the 20-hour study, number of occlusions. Participants will also be asked about perception of pain during insertion, overall acceptance of insertion, acceptance of catheter during the 20-hour admission, and for an overall preference between the new method and conventional blood sampling. In addition, participants will be contacted one week after admission regarding problems related to catheter insertion such as haematomas, pain, infection.

Secondary outcomes will be to assess the validity of cortisol concentrations measured by Dried Blood Spot technology, i.e. the Fluispotter®, compared to the standard blood sampling technique in a clinical setting. Also, Study 1 will compare diurnal cortisol profiles in healthy adults and patients with secondary adrenal insufficiency as well as assessing if the Fluispotter® performs the planned sampling.

Participants In Study 1 a total of 20 individuals will be included, 10 of whom (5 healthy women and 5 healthy men) will constitute the healthy adults and will be recruited through media advertisements.

Five women and 5 men diagnosed with secondary adrenal insufficiency due to pituitary disease will be recruited as patients.These 10 participants will constitute the patient group

The intervention takes place at the Department of Endocrinology and Metabolism at Rigshospitalet, Copenhagen, Denmark.

Sampling Sampling from the Fluispotter® is automatic and does not require attendance from staff. The Fluispotter® will be programmed for 20 samplings at 11:00 am, 13:00 p.m., 17:00 p.m., 21:00 p.m., 23:00 p.m., 00:50 a.m., 02:00 a.m., 02:50 a.m., 04:00 a.m., 04:30 a.m., 05:00 a.m., 05:30 a.m., 06:00 a.m., 06:15 a.m., 06:30 a.m., 06:45 a.m., 07:00 a.m., 07:15 a.m., 07:30 a.m. and 08:00 a.m. The cassettes containing the dried blood spots will be stored at -80◦C until analysis.

Also, eighteen samples from the venous catheter will be drawn at 11:00 am, 13:00 p.m., 17:00 p.m., 21:00 p.m., 23:00 p.m., 01:00 a.m., 03:00 a.m., 04:00 a.m., 04:30 a.m., 05:00 a.m., 05:30 a.m., 06:00 a.m., 06:15 a.m., 06:30 a.m., 06:45 a.m., 07:00 a.m., 07:15 a.m., 07:30 a.m. and 08:00 a.m.

One week after admission the patients will be scheduled for a post-intervention interview. At this visit the patients' arms will be checked for haematomas and the patients will be asked about possible health problems occurring which have arisen after the admission.

• Study Type: Observational
• Enrollment (Estimated): 20

Contacts and Locations

• Study Contact: Name: Ulla Feldt-Rasmussen, Professor; Phone Number: +45 35 45 10 23; Email: ufeldt@rh.dk
• Study Contact Backup: Name: Jesper Krogh, Ass. Prof; Phone Number: +45 25 53 54 85; Email: jesper.krogh.01@regionh.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with secondary pituitary insufficiency

Description

Healthy subjects

Inclusion Criteria:

• Not receiving regular medication
• Not receiving oral contraceptives or other oestrogens
• No known endocrine or major medical diseases
• No previous surgery of endocrine glands
• No regular smoking
• Not working nightshifts within the last 14 days before assessment
• Able to understand verbal and written instructions in Danish
• Able and willing to sign informed consent
• A negative pregnancy test one-week prior to admission
• Normal infection-, electrolyte- and coagulation-status assessed by standard blood samples

Patients Inclusion criteria

• Adrenal insufficiency due to pituitary disease
• No previous hormone producing pituitary adenomas
• Not receiving oral contraception or other oestrogens
• Stabil pituitary hormone replacement therapy, including hydrocortisone, for the previous three months
• No cardiac, respiratory or lung disease.
• No other disease that potentially requires additional hydrocortisone supplementation
• No regular smoking
• Not working nightshifts within the last 14 days before assessment
• Able to understand verbal and written instructions in Danish
• Able and willing to sign informed consent
• A negative pregnancy test 1-week prior to admission
• Normal infection-, electrolyte- and coagulations-status assessed by standard blood samples

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with adrenal insufficiency; 10 patients with adrenal insufficiency due to pituitary desease will be recruited for this arm.	Device: Fluispotter®; The Fluispotter® has been developed for automated extraction, collection and storage of up to 20 dried venous dried blood spot samples of 3-10 μl over the course of up to 20 hours. The system is attached to the patient through a multilumen microcatheter inserted into a peripheral vein in the arm. The Fluispotter will be inserted in both healthy subjects and patients with adrenal insufficiency.
Healthy controls; 10 healthy controls will be recruited for this arm.	Device: Fluispotter®; The Fluispotter® has been developed for automated extraction, collection and storage of up to 20 dried venous dried blood spot samples of 3-10 μl over the course of up to 20 hours. The system is attached to the patient through a multilumen microcatheter inserted into a peripheral vein in the arm. The Fluispotter will be inserted in both healthy subjects and patients with adrenal insufficiency.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility - subjects	Subjects' acceptance of device - Assessed by a questionnaire consisting of 11 questions designed for this study	Day 2-7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of succesfull samples by the Fluispotter	The Fluispotter is designed to collect 20 samples during 20 hours. This outcome will describe have many succesful samples the Fluispotter on average performed.	Day 2
Feasibility - operator	How did the anesthesiologist inserting the Fluispotter catheter percieve the feasibility of the device - Assessed by a questionnaire (uploaded)	Day 1

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Increase of cortisol due to sampling stress	The samples obtained from the Fluispotter willl be compared with wet samples prior to and after collection of samples. Any difference could be attribued to sampling stress.	through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark
• Investigators: Principal Investigator: Ulla Feldt-Rasmussen, Prof, Rigshospitalet, Denmark

Publications and helpful links

General Publications

• Ollerenshaw JD, Schroder M, Velschow S. A novel device for serial venous blood sampling in a canine model. J Pharmacol Toxicol Methods. 2022 Mar-Apr;114:107155. doi: 10.1016/j.vascn.2022.107155. Epub 2022 Jan 14.
• Adhikari KB, Rohde M, Velschow S, Feldt-Rasmussen U, Johannesen J, Johnsen AH. Fluispotter, a novel automated and wearable device for accurate volume serial dried blood spot sampling. Bioanalysis. 2020 May;12(10):665-681. doi: 10.4155/bio-2020-0048. Epub 2020 Jun 3.

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2023
• Primary Completion (Estimated): November 1, 2024
• Study Completion (Estimated): November 1, 2025

Study Registration Dates

• First Submitted: August 26, 2022
• First Submitted That Met QC Criteria: June 26, 2023
• First Posted (Actual): July 6, 2023

Study Record Updates

• Last Update Posted (Actual): July 6, 2023
• Last Update Submitted That Met QC Criteria: June 26, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Adrenal Gland Diseases; Adrenal Insufficiency
• Other Study ID Numbers: FLUISPOTTER

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There are currently no plan to share IPD with other researchers

Drug and device information, study documents

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