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

Healthy Volunteers Clinical Trial

— Echo-Os  

Official title:

Use of Intraosseous Doppler Ultrasonography to Study Skeletal Physiology - Echo-Os Study: Exploratory Study Before Its Use in Space Physiology

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06206031
• Other study ID #: 49RC23_0347
• Secondary ID: 2023-A02403-42
• Status: Not yet recruiting
• Phase: N/A
• Start date: January 29, 2024
• Est. completion date: February 8, 2025

Study information

• Verified date: January 2024
• Source: University Hospital, Angers
• Contact: Marc-Antoine CUSTAUD, Professor
• Phone: +33 2 41 35 63 57
• Email: MACustaud[@]chu-angers.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 32
• Est. completion date: February 8, 2025
• Est. primary completion date: January 29, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 20 Years to 70 Years

Eligibility

Inclusion Criteria for sub-protocol 1:

• Male aged 20-40 years

Inclusion criteria for sub-protocol 2:

• 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)

Inclusion criteria common for both sub-protocols:

• 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

Non-Inclusion criteria:

• 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.)

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Device:
• 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): donning in standing position - rest 1 minute - occlusion to 20 mmHg 2 minutes - 10 dorsiflexions - rest 1 minute - occlusion to 30 mmHg 2 minutes - 10 dorsiflexions - rest 1 minute - occlusion to 40 mmHg 2 minutes - 10 dorsiflexions - rest 1 minute - occlusion to 90 mmHg 2 minutes - 10 dorsiflexions - rest 1 minute - occlusion to 180 mmHg 2 minutes - doffing - sitting down for computed tomography 10 minutes.

Locations

Country	Name	City	State
France	CHU d'Angers	Angers
France	CHU de Saint-Etienne	Saint-Étienne

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Angers

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change in leg skin and muscle blood flow, induced by physiological maneuvers in supine position (sub-protocol 1)	Leg skin blood flow (arbitrary units), leg muscle change in concentrations of oxy- and deoxy-hemoglobin (µmol/L), and their responses to venous occlusion, arterial occlusion, handgrip, will be assessed via Laser Doppler flowmetry and Near-Infrared Spectroscopy	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	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)	Responses of leg intracortical, skin, and muscle blood flow to venous occlusion, arterial occlusion, and handgrip will be expressed as % baseline. Correlation of bone responses to skin and muscle responses (Pearson r) will be calculated.	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	Reproducibility of the change in tibial intracortical blood flow velocity, induced by physiological maneuvers in supine position (sub-protocol 1)	Measurements for sub-protocol 1 will be performed 2 times (visit 1 and visit 2 with 2-to-10-day interval), and Coefficient of variation in responses to physiological maneuvers (%) will be calculated	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	Change in tibial intracortical blood flow velocity, induced by occlusion maneuvers in standing position (sub-protocol 2)	Velocity (mm/s) of intracortical blood flow at distal tibia level, and its responses to proximal cuff compression steps of 20, 30, 40, 90, & 180 mmHg, will be assessed via Ultrasound Vector Flow Mapping.	Ultrasonography acquisition sequences of 5 secondes will be performed In standing position before and at the end of each occlusion step. Each occlusion lasts for 2 minutes. Between occlusions subject performs 10 dorsiflexions and stays still for 1 minute
Secondary	Comparison of intraosseous ultrasonography and computed tomography for Cortical bone porosity characterisation in standing position (sub-protocol 2)	Cortical density (mg/cm3) via peripheral quantitative computed tomography and cortical ultrasound propagation velocity (m/s) via intraosseous ultrasonography will be measured at distal tibia. Correlation (Pearson r) between measurements will be calculated.	First, intraosseous ultrasonography is performed in standing position (30 minutes for all occlusion steps), then the subject sits down and tomography is performed (10 minutes)
Secondary	Comparison of intraosseous ultrasonography and computed tomography for Cortical bone thickness characterisation (sub-protocol 2)	Cortical thickness at distal tibia (mm) will be measured via peripheral quantitative computed tomography and via intraosseous ultrasonography. Correlation (Pearson r) between measurements will be calculated	First, intraosseous ultrasonography is performed in standing position (30 minutes for all occlusion steps), then the subject sits down and tomography is performed (10 minutes)