Intraosseous Doppler Ultrasonography to Study Skeletal Physiology: Exploratory Study Before Use in Space Physiology

NCT ID: NCT06206031

Last Updated: 2025-10-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-04
• Study Completion Date: 2024-10-17

Brief Summary

Use of intraosseous Doppler ultrasonography to study skeletal physiology ("Echo-Os Study"). Exploratory study before its use in space physiology.

Bones have a complex vascular network providing nutrients and oxygen to bone cells. The physiology of intraosseous blood circulation remains very little known to date, particularly in human. Human bone vascularization studying is very difficult because of a lack of simple tools for functional exploration of bone vascular perfusion. For blood flow studies, ultrasonography is best suited, allowing for dynamic non-invasive measures. Bone has until now been considered to stop ultrasound and therefore prevent any intraosseous measurements. From a physics viewpoint, bones conduct ultrasound waves well, but they are reflected differently compared to soft tissues. A specific analysis of the ultrasound returned by the bone, using specific correction factors, is therefore needed to interpret ultrasound signals, reconstruct an anatomical image, and extract physiological information. The system proposed in this study combines standard conventional low-frequency ultrasound probes with a specific analysis of ultrasound wave reflection. This system makes it possible to reconstruct an anatomical bone image and record the pulsatile signal of intraosseous vascular perfusion. The investigators will use this system to study the vascular reactivity induced by different physiological maneuvers.

This protocol proposes to study the following mechanisms of blood flow regulation at the level of tibia cortical bone: flow-mediated dilation induced by endothelium (with arterial occlusion test), vasoconstriction induced by sympathetic activation (with static handgrip test), and vasoconstriction induced by veno-arteriolar reflex (with venous occlusion test). This is a pilot study in physiology performed with healthy volunteers. This study will verify whether our intraosseous ultrasound system can properly measure physiological responses expected during these maneuvers. This protocol will also establish links between perfusion and bone architecture at tibial level.

Conditions

Healthy Volunteers

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

"Intraosseous ultrasonography"

All subjects of each sub-protocol receive identical intervention (single group assignment for each of 2 sub-protocols).

Group Type: EXPERIMENTAL

Intraosseous ultrasonography at tibia before, during, and after a physiological vascular stimulation (venous occlusions, arterial occlusion, handgrip)

Intervention Type: DEVICE

Timing for sub-protocol 1 (performed twice with 2-to-10-day interval): donning in supine position - rest 5 minutes - venous occlusion to 40 mmHg 3 minutes - rest 10 minutes - arterial occlusion to 200mmHg 2 minutes - post-occlusion period 10 minutes - rest 10 minutes - static handgrip 30% Maximum Voluntary Force 3 minutes - recovery 2 minutes and doffing.

Timing for sub-protocol 2 (performed once). First, two sequences of intraosseous ultrasonography are performed in 45° head-up tilt position, with 10-minutes rest between sequences: donning and rest 5 minutes - occlusion to 80 mmHg 2 minutes - rest 10 minutes - occlusion to 180 mmHg 2 minutes - rest 10 minutes. During the first sequence, ultrasonography probe is positioned between middle and lower third of tibia for cortical bone measurement; during the second - at distal epiphysis of the tibia for trabecular bone measurement. After ultrasonography, subject is sitting down for 10 minutes for computed tomography.

Interventions

Intraosseous ultrasonography at tibia before, during, and after a physiological vascular stimulation (venous occlusions, arterial occlusion, handgrip)

Timing for sub-protocol 1 (performed twice with 2-to-10-day interval): donning in supine position - rest 5 minutes - venous occlusion to 40 mmHg 3 minutes - rest 10 minutes - arterial occlusion to 200mmHg 2 minutes - post-occlusion period 10 minutes - rest 10 minutes - static handgrip 30% Maximum Voluntary Force 3 minutes - recovery 2 minutes and doffing.

Timing for sub-protocol 2 (performed once). First, two sequences of intraosseous ultrasonography are performed in 45° head-up tilt position, with 10-minutes rest between sequences: donning and rest 5 minutes - occlusion to 80 mmHg 2 minutes - rest 10 minutes - occlusion to 180 mmHg 2 minutes - rest 10 minutes. During the first sequence, ultrasonography probe is positioned between middle and lower third of tibia for cortical bone measurement; during the second - at distal epiphysis of the tibia for trabecular bone measurement. After ultrasonography, subject is sitting down for 10 minutes for computed tomography.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Male aged 20-40 years

• Male aged 20-40 years & 50-70 years
• Body height of at least 180 cm (in order to have tibia length of 43-45 cm allowing the positioning of ultrasonic probe at distal tibia, and occlusive cuff at calf level)
• Bone densitometry with available report performed within 5 last years (if none has been done, possibility to perform densitometry covered by the study at selection or inclusion visit)

• Healthy volunteer without chronic pathology (in particular no known rhythm disorder) or long-term treatment
• No symptomatic acute medical event requiring treatment on the visit days
• No history of tibia fractures
• Body Mass Index between 19 and 26
• Affiliation to the French Social Security System
• Written informed consent

• Inability to stay still for 20 minutes (tremor)
• Active smoking (stopped less than 1 year ago)
• History of prolonged corticosteroid treatment
• Deprivation of liberty by legal or administrative decision
• Subject to involuntary psychiatric treatment
• Subject to a legal protection measure
• For sub-study 1: Osteoporosis known at interview

Exclusion Criteria

• Any abnormality or deviation from the selection criteria identified during the clinical examination at the inclusion visit (non-sinus rhythm in ECG, body temperature > 38°C, blood pressure or heart rate outside the defined standards, etc.)

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

University Hospital, Angers

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marc-Antoine CUSTAUD, Professor

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Angers

Locations

CHU d'Angers

Angers, , France

CHU de Saint-Etienne

Saint-Etienne, , France

Countries

France

Other Identifiers

2023-A02403-42

Identifier Type: OTHER

Identifier Source: secondary_id

49RC23_0347

Identifier Type: -

Identifier Source: org_study_id