Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05752825 |
| Other study ID # |
N-20220041 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
June 2, 2023 |
| Est. completion date |
May 15, 2024 |
Study information
| Verified date |
May 2024 |
| Source |
Aalborg University Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial 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.
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 www.forsoegsperson.dk. 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 scanner's 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 0,003 -
0,005 mSv, which is considered a low radiation dose33. In comparison, a regular chest X-ray
yields a dose of 0,01 - 0,1 mSv and dental X-ray yields 0,005 mSv. The worldwide average
effective radiation dose from natural background radiation is 2,4 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 0,001 and 0,01 mSv for one whole body DXA scan,
between 0,003 and 0,03 mSv for one hip and lumbar spine DXA scan and 0,003 mSv for one VFA
scan. As such, the total effective radiation dose for the DXA scans is between 0,007 and
0,043 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 and/or 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 >13,5 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 open/closed 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.
