Ignite Creation Date:
2024-05-06 @ 6:41 PM
Last Modification Date:
2024-10-26 @ 2:53 PM
Study NCT ID:
NCT05752825
Status:
COMPLETED
Last Update Posted:
2024-05-16
First Post:
2023-02-22
Brief Title:
Acromegaly Balance Falls and Fracture Risk
Sponsor:
Christian Alexander H Rosendal
Organization:
Aalborg University Hospital
Study Overview
Official Title:
Acromegaly Balance Falls and Fracture Risk
Status:
COMPLETED
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The goal of this observational cross-sectional study is to study bone quality joint quality and fall risk in acromegalic patients compared with healthy controls The main questions it aims to answer are
what is the optimal method for evaluating bone quality and fracture risk in acromegalic patients
are acromegalic patients at increased risk of falling
is HR-pQCT a feasible method for evaluating acromegalic joint disease Participants will undergo HR-pQCT scans DXA scans OsteoProbe examination and fall risk assessments Results will be compared to matched healthy controls
what is the optimal method for evaluating bone quality and fracture risk in acromegalic patients
are acromegalic patients at increased risk of falling
is HR-pQCT a feasible method for evaluating acromegalic joint disease Participants will undergo HR-pQCT scans DXA scans OsteoProbe examination and fall risk assessments Results will be compared to matched healthy controls
Detailed Description:
Patients with an established diagnosis of acromegaly will be recruited from March 2023 to March 2025 Patients will be informed of the study during scheduled visits to the pituitary endocrinology outpatient clinic at Aalborg University Hospital by one of two specialists in pituitary endocrinology Patients will be given information regarding the study and if interested they will be provided with a form to fill out with their contact information so they can be contacted by the investigators or other staff affiliated with the study Should the patient agree to be contacted via telephone or e-mail they will be given an instruction regarding their rights as a participant in a scientific study Dine rettigheder som forsøgsperson i et sundhedsvidenskabeligt forskningsprojekt as well as written material specifically pertaining to the study Deltagerinformation Should the subject be deemed fit for the study based on the in- and exclusion criteria contact will be made via phone or e-mail and they will receive further information regarding the study and offered a personal meeting with one of the investigators where details of the study procedures will be outlined The meeting will take place in a dedicated undisturbed office at the disposition of the Department of Endocrinology in order to ensure due privacy during the meeting In advance the subject will be informed of the opportunity to bring a relative or other representative to the meeting At the meeting the participant and any representative will be informed of the 24-hour deliberation period before providing informed consent No study procedures will be performed until the informed consent form has been signed by both the participant and the investigator
As mentioned above healthy controls will be recruited via the aforementioned database social media and websites such as wwwforsoegspersondk Potential participants who contact the principal investigator through these channels will be provided with written material pertaining to the study Deltagerinformation and a description of their legal rights as a participant Dine rettigheder som forsøgsperson i et sundhedsvidenskabeligt forskningsprojekt Should the potential participant meet the in- and exclusion criteria they will be invited to a personal meeting where details of the study are explained having been informed of the opportunity to bring a representative or relative to the meeting in advance Should they wish to participate a 24-hour deliberation period will be given prior to obtaining written informed consent
After providing informed consent the participants will undergo a series of study procedures Bone quality will be assessed by way of High-Resolution peripheral Quantitative Computed Tomography HR-pQCT images of the distal radius and tibia Bone material strength index BMSi is assessed using an OsteoProbe In addition to this postural control will be assessed using a balance board to obtain a surrogate measure of fall risk Body composition bone mineral density and vertebral fracture assessment VFA will be analyzed via Dual X-ray Absorptiometry DXA scans and peripheral muscle strength will be assessed via hand grip strength and knee extension torque measurements and visual acuity tested with standard methods Data will be analyzed using relevant statistical analyses and presented as a cross-sectional study
HIGH RESOLUTION PERIPHERAL QUANTITATIVE COMPUTED TOMOGRAPHY HR-PQCT HR-pQCT is a 3-dimensional imaging modality that can be applied to bone and joints in vivo in order to non-invasively assess the quantity and quality of trabecular and cortical bone compartments separately HR-pQCT will be applied to peripheral skeletal sites namely the distal radius and tibia where image slices equivalent to 9 mm of bone will be acquired From this parameters such as volumetric bone mineral density vBMD cortical density cortical porosity trabecular density trabecular thickness trabecular spacing and others will be calculated using specialized software In the same scanning session images of the wrist and ankle joints will be produced and analyzed for features of arthrosis such as erosions osteophytosis and others
The scanners gantry is relatively narrow and shallow rear physical stop only allowing the distal peripheral skeleton to be accommodated The limb being scanned is immobilized in a carbon fiber shell A scout view essentially a two-dimensional x-ray scan is obtained so that the operator can identify a precise region for the three-dimensional measurement Because HR-pQCT uses a polychromatic X-ray source it is subject to beam hardening as well as scatter artefacts which can significantly impact geometric and densitometric measures Once the images have been acquired a default patient evaluation protocol is used to analyze the scans over the entire 9 mm three-dimensional region to assess a wide range of standard and optional structural and density parameters
The effective radiation dose for one HR-pQCT scan at the distal tibia or radius is 0003 - 0005 mSv which is considered a low radiation dose33 In comparison a regular chest X-ray yields a dose of 001 - 01 mSv and dental X-ray yields 0005 mSv The worldwide average effective radiation dose from natural background radiation is 24 mSv per year The average effective radiation dose in Denmark is 3 mSv per year
Estimated time 30 min WHOLE BODY DUAL X-RAY ABSORPTIOMETRY DXA SCAN AND VERTEBRAL FRACTURE ASSESSMENT Through DXA scans we will obtain information regarding body composition hip and spine bone mineral density as well as examine any previous vertebral fractures using vertebral fracture assessment VFA VFA is a function of DXA scanners which allows for visualization of thoracic and lumbar vertebrae usually T4-L4 in order to detect vertebral fractures34 Vertebral fractures can then be classified as either mild moderate or severe using the method described by Genant et al35
The effective radiation dose is between 0001 and 001 mSv for one whole body DXA scan between 0003 and 003 mSv for one hip and lumbar spine DXA scan and 0003 mSv for one VFA scan As such the total effective radiation dose for the DXA scans is between 0007 and 0043 mSv
The whole body DXA scan hip and lumbar spine DXA scan and VFA scan will be performed consecutively
Estimated time 50 min MICROINDENTATION BONE MATERIAL STRENGTH INDEX BMSI AND THE OSTEOPROBE Using the OsteoProbe we will by microindentation measure the bone material strength index BMSi an in vivo surrogate measure of the fracture resistance of the cortical bone in the tibia The participant is placed in a supine position with the examined leg rotated slightly outward After identifying the site of interest located midway between the medial tibial plateau and the medial malleolus disinfectant is applied to the skin of the tibia being examined Finally under local anesthesia and fully sterile conditions a test probe is inserted through the skin and onto the midshaft of the tibia and the fracture resistance of the bone tissue is measured Without removing the probe from the skin this process is repeated a minimum of eight maximally 18 times to provide a sufficient number of measurements By means of a synthetic polymer calibration phantom the BMSi is calculated via specialized software provided by the manufacturer After the procedure a sterile bandage will be applied to the puncture site and all sharp andor biohazardous materials will be disposed of in an appropriate manner
Estimated time 20 min HAND GRIP STRENGTH HGS AND LEG EXTENSION STRENGTH Hand grip strength will be assessed using a digital hand dynamometer as a measure of peripheral muscle strength Leg extensor strength will be examined using the peak torque measured by an isometric dynamometer mounted on a fixed chair 3 attempts will be given for each method and the maximum value recorded
Estimated time 10 min TIMED UP-AND-GO TUG The TUG test is a functional test frequently used to assess balance in older individuals and is performed by measuring the time it takes for an individual to go from sitting to standing position walk 3 meters turn around and return to sitting position A TUG score of 135 seconds is associated with an increased risk of falls
Estimated time 10 min STABILOMETRY Postural control will be assessed by means of a force platform that registers Center of Pressure CoP as a measure of postural stability Measurements are performed under a variety of conditions including eyes openclosed and on different surfaces From the CoP measurements parameters such as CoP range and CoP velocity in both antero-posterior and medial-lateral directions will be calculated using specialized software
Estimated time 20 min NERVE CONDUCTION TEST To fully examine all components of balance nerve conduction will be tested using a handheld device called NC-stat DPN-Check in order to assess any peripheral neuropathy
Estimated time 10 min VISUAL ACUITY TEST Visual acuity will be tested using an automated refractometer KR-800S Auto-kerato-refractometer Topcon Healthcare The Netherlands
Estimated time 10 min Our laboratory has ample experience and know-how regarding the above-mentioned methods and their application in different patient groups
QUESTIONNAIRES Through questionnaires we will obtain information regarding previous falls and fractures overall quality of life Acro-QoL joint-related symptoms Western Ontario and McMaster universities osteoarthritis Index WOMAC fear of falling Falls Efficacy Scale International FES-I and balance Berg Balance Scale Medicine lists will be collected from all participants
BIOCHEMICAL BONE MARKERS AND BLOOD SAMPLES To assess biochemical markers of bone metabolism we will measure fasting serum levels of procollagen-1 N-terminal propeptide P1NP a marker of bone formation and cross-linked C telopeptide of type I collagen CTX a marker of bone resorption as well as sclerostin an inhibitor of bone formation To assess other hormones with influence on bone quality we will measure levels of vitamin D and parathyroid hormone PTH In total a volume of approximately 16mL of blood 4x 4mL vials will be collected from each participant both acromegalic and controls For practical reasons these blood samples are frozen after collection stored in a research biobank and analyzed in one session upon all participants completion of the study procedures Before analysis Danish Tissue Utilization Register Vævsanvendelsesregistret will be consulted should the participant be listed herein the blood sample will not be analyzed After analysis any remaining material will be destroyed
Two extra vials of blood 10mL total will be extracted and stored in a biobank for future research to enable analysis of any future bone markers or other biomarkers of interest for this project An application will be submitted to the Danish Data Protection Agency in this regard Blood samples will be frozen and stored in an encrypted fashion and in compliance with the Danish Data Protection Act for 15 years after completion of the study or until their destruction is requested by the participant Blood samples will be collected from both acromegalic subjects and healthy controls in order to determine differences in biochemical markers between acromegalic subjects and control subjects Participants will be asked to sign a separate consent form regarding storage of their biological material blood sample in a biobank for future research
All blood samples are stored in a freezer at -80 degrees Celsius
As mentioned above healthy controls will be recruited via the aforementioned database social media and websites such as wwwforsoegspersondk Potential participants who contact the principal investigator through these channels will be provided with written material pertaining to the study Deltagerinformation and a description of their legal rights as a participant Dine rettigheder som forsøgsperson i et sundhedsvidenskabeligt forskningsprojekt Should the potential participant meet the in- and exclusion criteria they will be invited to a personal meeting where details of the study are explained having been informed of the opportunity to bring a representative or relative to the meeting in advance Should they wish to participate a 24-hour deliberation period will be given prior to obtaining written informed consent
After providing informed consent the participants will undergo a series of study procedures Bone quality will be assessed by way of High-Resolution peripheral Quantitative Computed Tomography HR-pQCT images of the distal radius and tibia Bone material strength index BMSi is assessed using an OsteoProbe In addition to this postural control will be assessed using a balance board to obtain a surrogate measure of fall risk Body composition bone mineral density and vertebral fracture assessment VFA will be analyzed via Dual X-ray Absorptiometry DXA scans and peripheral muscle strength will be assessed via hand grip strength and knee extension torque measurements and visual acuity tested with standard methods Data will be analyzed using relevant statistical analyses and presented as a cross-sectional study
HIGH RESOLUTION PERIPHERAL QUANTITATIVE COMPUTED TOMOGRAPHY HR-PQCT HR-pQCT is a 3-dimensional imaging modality that can be applied to bone and joints in vivo in order to non-invasively assess the quantity and quality of trabecular and cortical bone compartments separately HR-pQCT will be applied to peripheral skeletal sites namely the distal radius and tibia where image slices equivalent to 9 mm of bone will be acquired From this parameters such as volumetric bone mineral density vBMD cortical density cortical porosity trabecular density trabecular thickness trabecular spacing and others will be calculated using specialized software In the same scanning session images of the wrist and ankle joints will be produced and analyzed for features of arthrosis such as erosions osteophytosis and others
The scanners gantry is relatively narrow and shallow rear physical stop only allowing the distal peripheral skeleton to be accommodated The limb being scanned is immobilized in a carbon fiber shell A scout view essentially a two-dimensional x-ray scan is obtained so that the operator can identify a precise region for the three-dimensional measurement Because HR-pQCT uses a polychromatic X-ray source it is subject to beam hardening as well as scatter artefacts which can significantly impact geometric and densitometric measures Once the images have been acquired a default patient evaluation protocol is used to analyze the scans over the entire 9 mm three-dimensional region to assess a wide range of standard and optional structural and density parameters
The effective radiation dose for one HR-pQCT scan at the distal tibia or radius is 0003 - 0005 mSv which is considered a low radiation dose33 In comparison a regular chest X-ray yields a dose of 001 - 01 mSv and dental X-ray yields 0005 mSv The worldwide average effective radiation dose from natural background radiation is 24 mSv per year The average effective radiation dose in Denmark is 3 mSv per year
Estimated time 30 min WHOLE BODY DUAL X-RAY ABSORPTIOMETRY DXA SCAN AND VERTEBRAL FRACTURE ASSESSMENT Through DXA scans we will obtain information regarding body composition hip and spine bone mineral density as well as examine any previous vertebral fractures using vertebral fracture assessment VFA VFA is a function of DXA scanners which allows for visualization of thoracic and lumbar vertebrae usually T4-L4 in order to detect vertebral fractures34 Vertebral fractures can then be classified as either mild moderate or severe using the method described by Genant et al35
The effective radiation dose is between 0001 and 001 mSv for one whole body DXA scan between 0003 and 003 mSv for one hip and lumbar spine DXA scan and 0003 mSv for one VFA scan As such the total effective radiation dose for the DXA scans is between 0007 and 0043 mSv
The whole body DXA scan hip and lumbar spine DXA scan and VFA scan will be performed consecutively
Estimated time 50 min MICROINDENTATION BONE MATERIAL STRENGTH INDEX BMSI AND THE OSTEOPROBE Using the OsteoProbe we will by microindentation measure the bone material strength index BMSi an in vivo surrogate measure of the fracture resistance of the cortical bone in the tibia The participant is placed in a supine position with the examined leg rotated slightly outward After identifying the site of interest located midway between the medial tibial plateau and the medial malleolus disinfectant is applied to the skin of the tibia being examined Finally under local anesthesia and fully sterile conditions a test probe is inserted through the skin and onto the midshaft of the tibia and the fracture resistance of the bone tissue is measured Without removing the probe from the skin this process is repeated a minimum of eight maximally 18 times to provide a sufficient number of measurements By means of a synthetic polymer calibration phantom the BMSi is calculated via specialized software provided by the manufacturer After the procedure a sterile bandage will be applied to the puncture site and all sharp andor biohazardous materials will be disposed of in an appropriate manner
Estimated time 20 min HAND GRIP STRENGTH HGS AND LEG EXTENSION STRENGTH Hand grip strength will be assessed using a digital hand dynamometer as a measure of peripheral muscle strength Leg extensor strength will be examined using the peak torque measured by an isometric dynamometer mounted on a fixed chair 3 attempts will be given for each method and the maximum value recorded
Estimated time 10 min TIMED UP-AND-GO TUG The TUG test is a functional test frequently used to assess balance in older individuals and is performed by measuring the time it takes for an individual to go from sitting to standing position walk 3 meters turn around and return to sitting position A TUG score of 135 seconds is associated with an increased risk of falls
Estimated time 10 min STABILOMETRY Postural control will be assessed by means of a force platform that registers Center of Pressure CoP as a measure of postural stability Measurements are performed under a variety of conditions including eyes openclosed and on different surfaces From the CoP measurements parameters such as CoP range and CoP velocity in both antero-posterior and medial-lateral directions will be calculated using specialized software
Estimated time 20 min NERVE CONDUCTION TEST To fully examine all components of balance nerve conduction will be tested using a handheld device called NC-stat DPN-Check in order to assess any peripheral neuropathy
Estimated time 10 min VISUAL ACUITY TEST Visual acuity will be tested using an automated refractometer KR-800S Auto-kerato-refractometer Topcon Healthcare The Netherlands
Estimated time 10 min Our laboratory has ample experience and know-how regarding the above-mentioned methods and their application in different patient groups
QUESTIONNAIRES Through questionnaires we will obtain information regarding previous falls and fractures overall quality of life Acro-QoL joint-related symptoms Western Ontario and McMaster universities osteoarthritis Index WOMAC fear of falling Falls Efficacy Scale International FES-I and balance Berg Balance Scale Medicine lists will be collected from all participants
BIOCHEMICAL BONE MARKERS AND BLOOD SAMPLES To assess biochemical markers of bone metabolism we will measure fasting serum levels of procollagen-1 N-terminal propeptide P1NP a marker of bone formation and cross-linked C telopeptide of type I collagen CTX a marker of bone resorption as well as sclerostin an inhibitor of bone formation To assess other hormones with influence on bone quality we will measure levels of vitamin D and parathyroid hormone PTH In total a volume of approximately 16mL of blood 4x 4mL vials will be collected from each participant both acromegalic and controls For practical reasons these blood samples are frozen after collection stored in a research biobank and analyzed in one session upon all participants completion of the study procedures Before analysis Danish Tissue Utilization Register Vævsanvendelsesregistret will be consulted should the participant be listed herein the blood sample will not be analyzed After analysis any remaining material will be destroyed
Two extra vials of blood 10mL total will be extracted and stored in a biobank for future research to enable analysis of any future bone markers or other biomarkers of interest for this project An application will be submitted to the Danish Data Protection Agency in this regard Blood samples will be frozen and stored in an encrypted fashion and in compliance with the Danish Data Protection Act for 15 years after completion of the study or until their destruction is requested by the participant Blood samples will be collected from both acromegalic subjects and healthy controls in order to determine differences in biochemical markers between acromegalic subjects and control subjects Participants will be asked to sign a separate consent form regarding storage of their biological material blood sample in a biobank for future research
All blood samples are stored in a freezer at -80 degrees Celsius
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None