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

NCT06206031 | Completed

• 2 other identifiers: 49RC23_03472023-A02403-42
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

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

Keywords

Bone blood circulation; Tibial cortical blood flow; Intraosseous ultrasound; Venous occlusion; Arterial occlusion

Outcome Measures

Primary Outcomes (1)

• Change in tibial intracortical blood flow velocity, induced by physiological maneuvers in supine position (sub-protocol 1)

  Velocity (mm/s) of intracortical blood flow at medial tibia level and its response to venous occlusion, arterial occlusion, handgrip, will be assessed via Ultrasound Vector Flow Mapping

  before, at the end of venous occlusion (40 mmHg 3 minutes); before, at the end of arterial occlusion (200 mmHg 2 min); at 2, 5, and 10 min of post-occlusion period; before, at the end of handgrip (30% maximum voluntary force for 3 minutes)

Secondary Outcomes (7)

• Change in leg skin and muscle blood flow, induced by physiological maneuvers in supine position (sub-protocol 1)

  before, at the end of venous occlusion (40 mmHg 3 minutes); before, at the end of arterial occlusion (200 mmHg 2 min); at 2, 5, and 10 min of post-occlusion period; before, at the end of handgrip (30% maximum voluntary force for 3 minutes)

• Comparison of changes in tibial intracortical blood flow with changes in leg skin and muscle blood flow, induced by physiological maneuvers in supine position (sub-protocol 1)

  before, at the end of venous occlusion (40 mmHg 3 minutes); before, at the end of arterial occlusion (200 mmHg 2 min); at 2, 5, and 10 min of post-occlusion period; before, at the end of handgrip (30% maximum voluntary force for 3 minutes)

• Reproducibility of the change in tibial intracortical blood flow velocity, induced by physiological maneuvers in supine position (sub-protocol 1)

  before, at the end of venous occlusion (40 mmHg 3 minutes); before, at the end of arterial occlusion (200 mmHg 2 min); at 2, 5, and 10 min of post-occlusion period; before, at the end of handgrip (30% maximum voluntary force for 3 minutes)

• Change in tibial intracortical blood flow velocity, induced by occlusion maneuvers in +45° head up tilt position (sub-protocol 2)

  Ultrasonography acquisition sequences of 5 secondes will be performed before and during each occlusions.

• Change in tibial ultradistal bone blood flow velocity, induced by occlusion maneuvers in +45° head up tilt position (sub-protocol 2)

  Ultrasonography acquisition sequences of 5 secondes will be performed before and during each occlusions.

Study Arms (1)

"Intraosseous ultrasonography"

EXPERIMENTAL

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

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

Interventions

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

"Intraosseous ultrasonography"

Eligibility Criteria

• Age: 20 Years - 70 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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

Sponsors & Collaborators

• University Hospital, Angers: lead

Study Sites (2)

CHU d'Angers

Angers, 49933, France

Location

CHU de Saint-Etienne

Saint-Etienne, 42055, France

Location

MeSH Terms

Conditions

Arterial Occlusive Diseases

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Study Officials

• Marc-Antoine CUSTAUD, Professor

  University Hospital, Angers

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: This small-n pilot study in physiology aims to validate the concept and serve a basis for in-depth studies on space physiology. Two clinical centers will be involved, each providing measurements in its area of expertise, and two sub-protocols with complementary objectives will be implemented: * Sub-protocol 1 (16 males of 20-40 yrs with usable data): Study of cortical bone vascular reactivity and its reproducibility at medial tibia (Angers University Hospital); * Sub-protocol 2 (16 males of 20-70 yrs with usable data): Study of bone perfusion at distal and ultradistal tibia, and comparison of bone measurements by ultrasound to those by peripheral quantitative computed tomography (Saint-Etienne University Hospital). Bone ultrasonography will be performed for both sub-protocols.

Study Record Dates

• First Submitted: January 4, 2024
• First Posted: January 16, 2024
• Study Start: March 4, 2024
• Primary Completion: October 17, 2024
• Study Completion: October 17, 2024
• Last Updated: March 9, 2026

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: The data will be shared after signing a negotiated data transfer agreement ( data access agreement), for the duration specified in the agreement.
• Access Criteria: The data will be made available via secure transfer (sharing platform approved by the university hospital: BlueFiles or Oodrive).

Locations

FR (2)