Clinical trial NCT06206031: Intraosseous Doppler Ultrasonography to Study Skeletal Physiology: Exploratory Study Before Use in Space Physiology
Official title: Use of Intraosseous Doppler Ultrasonography to Study Skeletal Physiology - Echo-Os Study: Exploratory Study Before Its Use in Space Physiology
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy Volunteers
Keywords: Bone blood circulation
Tibial cortical blood flow
Intraosseous ultrasound
Venous occlusion
Arterial occlusion
Lead sponsor: University Hospital, Angers
Sponsor class: OTHER_GOV
First posted: 2024-01-16
Enrollment: 30
Sex: MALE
Minimum age (years): 20
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 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.
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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.)

Primary outcomes:
measure: Change in tibial intracortical blood flow velocity, induced by physiological maneuvers in supine position (sub-protocol 1)
timeFrame: 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:
measure: Change in leg skin and muscle blood flow, induced by physiological maneuvers in supine position (sub-protocol 1)
timeFrame: 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)
measure: 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)
timeFrame: 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)
measure: Reproducibility of the change in tibial intracortical blood flow velocity, induced by physiological maneuvers in supine position (sub-protocol 1)
timeFrame: 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)
measure: Change in tibial intracortical blood flow velocity, induced by occlusion maneuvers in +45° head up tilt position (sub-protocol 2)
timeFrame: Ultrasonography acquisition sequences of 5 secondes will be performed before and during each occlusions.
measure: Change in tibial ultradistal bone blood flow velocity, induced by occlusion maneuvers in +45° head up tilt position (sub-protocol 2)
timeFrame: Ultrasonography acquisition sequences of 5 secondes will be performed before and during each occlusions.
measure: Comparison of intraosseous ultrasonography and computed tomography for Cortical bone thickness characterisation (sub-protocol 2)
timeFrame: First, intraosseous ultrasonography is performed at +45° head up tilt position (30 minutes for all occlusion steps), then the subject sits down and tomography is performed (10 minutes)
measure: Comparison of intraosseous ultrasonography and computed tomography for Cortical bone porosity characterisation (sub-protocol 2)
timeFrame: First, intraosseous ultrasonography is performed at +45° head up tilt position (30 minutes for all occlusion steps), then the subject sits down and tomography is performed (10 minutes)
Other outcomes:
Locations:
city: Angers
country: France
facility: CHU d'Angers
city: Saint-Étienne
country: France
facility: CHU de Saint-Etienne
Study officials:
affiliation: University Hospital, Angers
name: Marc-Antoine CUSTAUD, Professor
role: PRINCIPAL_INVESTIGATOR
References: