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Primary Objective: Determination of risk factors for hand function impairment in systemic sclerosis (SSc) patients with early disease, very early disease and established hand impairment (contractures) at 2 years follow-upSecondary Objective(s):-…
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Ethical review
Approved WMO
Status
Recruiting
Health condition type
Autoimmune disorders
Study type
Observational invasive
Source
ToetsingOnline
Brief title
HANDSOME study
Condition
- Autoimmune disorders
- Connective tissue disorders (excl congenital)
Synonym
scleroderma, Systemic sclerosis
Research involving
Human
Sponsors and support
Primary sponsor :
Universitair Medisch Centrum Utrecht
Source(s) of monetary or material Support :
Reuma Nederland
Intervention
Keyword :
Function, Hand, Imaging, Scleroderma
Outcome measures
Primary outcome
- The change in hand function over time and development of impairment at 2
years, measured with:
- Range of motion (ROM) wrists
- Range of motion (ROM) finger joints
- Delta finger to palm distance (dFTP)
- The modified HAMIS (mHAMIS)
- Hand grip strength (JAMAR, JAMAR punch 1-2 and lateral grip)
- The Cochin Hand Function Scale (CHFS).
- Predictive value of imaging features and biomarkers in serum and tissue at
baseline for (change in) extent of hand impairment at follow-up
- Predictive value of biomarkers in serum and tissue; immunological markers and
markers for fibrogenesis in serum, in relation to features on ultrasound,
elastography and MRI for (change in) level of hand impairment at follow-up
Secondary outcome
- Imaging characteristics on US and MRI images:
- Compared between groups (SSc patients with versus without hand
impairment, SSc versus VEDOSS patients)
- Compared between patients with and without developing hand
impairment at follow-up
- related to each other
- Hand impairment (measured as described above) in dominant versus non-dominant
hand.
- health-related quality of life (EQ5D-5L), daily functioning (S-HAQ), hand
function (CHFS) and hand function measures over time
- Change in PASTUL (skin self-assessment) over time and relation to mRSS and
hand function measures
- Disease severity; Progression from VEDOSS to SSc established disease
(according to the 2013 EULAR-ACR criteria)
- Shear wave elastography and hand function measures at baseline and at 2 years
follow-up
Background summary
Almost 90% of systemic sclerosis (SSc) patients experience hand function
limitation, which leads to impaired daily functioning and work participation.
An important cause of impaired hand function are contractures of the hand,
which are reported in half of patients. Contractures were more frequent in
patients with diffuse cutaneous systemic sclerosis (dcSSc) and in the dominant
hand, and associated with anti-topoisomerase I (ATA) positivity. Only few
studies explored imaging techniques in SSc hands. Thickening of the A1 pully of
flexor tendons and flexor tendons was associated with hand disability in 29
patients and soft tissue calcifications were seen in affected tendons, but this
has not been studied in more detail. Furthermore, ultrasound and MRI showed
subclinical synovitis or tendinitis and erosions, which could contribute to
impaired hand function as well. Shear wave elastography (SWE), a new imaging
modality, has been studied in SSc skin and muscles but no studies have assessed
hand tendons. Moreover, no studies investigated tenosynovial changes and
underlying biological mechanisms, especially not in correlation with imaging or
functional tests. This leaves clinicians *in the dark* regarding diagnostic
work-up and effective management. Current management for hand symptoms includes
exercises, splints, and sometimes immunosuppressive therapies. However, it is
not known which treatment is applicable for which patient and efficacy of
immunosuppressive drugs has not been confirmed in trials. As impaired hand
function in SSc hugely impacts quality of life and daily functioning, there is
a high unmet need for effective treatments. With the availability of new
imaging modalities, biomarkers and lab techniques, opportunities arise to
tackle this problem.
Study objective
Primary Objective:
Determination of risk factors for hand function impairment in systemic
sclerosis (SSc) patients with early disease, very early disease and established
hand impairment (contractures) at 2 years follow-up
Secondary Objective(s):
- Identify underlying mechanisms leading to hand function impairment and
contractures in patients with VEDOSS (very early diagnosis of systemic
sclerosis ) and SSc with and without contractures and in different disease
subsets in order to guide future research into new targets for personalized
treatment in this heterogeneous disease.
a. Explore differences in serum biomarkers for inflammation,
vasculopathy and fibrosis in relation to hand function impairment and
contractures
and imaging features.
b. Identify subgroups based on clinical, immunological, and imaging
characteristics.
- Validation of the Dutch PASTUL questionnaire, and assessment of benefit of
self-assessment of skin in relation to hand function impairment
Study design
This is a longitudinal observational multicenter study in patients with VEDOSS
and SSc who are seen at the outpatient clinic of the Department of Rheumatology
& Clinical Immunology of the University Medical Centre Utrecht (UMCU), st
Antoniushospital Nieuwegein, UMC Groningen (UMCG) Leiden UMC (LUMC), Radboud
UMC, or Royal Free Hospital (RFH) London. Patients will be followed for 2
years.
Study burden and risks
There are four study visits; at start, 6 months, 12 months and 24 months.
During the visits, participants are seen by a doctor-researcher or research
nurse who takes hand function measurements and skin score (40 minutes),
followed by ultrasound and elastography (40 minutes) and blood is taken (15
minutes). During the first study visit, an MRI of the hands will be performed
on participants from the UMC Utrecht. This will take approximately 45 minutes.
If desired, the study visits will be combined as much as possible with regular
checks, so that travel time is limited. Participants receive an invitation for
an online questionnaire (20 minutes) that they can complete around the study
visits, at a location and time that suits them best.
Participation in this study does not entail any significant risks. No
experimental treatment is given and imaging (ultrasound, MRI) does not cause
radiation exposure. Blood collection via venipuncture will take place four
times, during which 10 ml of blood will be taken. For comparison: when donating
blood at the blood bank, 500 ml of blood is taken in one go. Blood collection
can sometimes be painful during the collection.
Public
Universitair Medisch Centrum Utrecht
Heidelberglaan 100
Utrecht 3584 CX
NL
Scientific
Universitair Medisch Centrum Utrecht
Heidelberglaan 100
Utrecht 3584 CX
NL
Listed location countries
Netherlands
Age
Adults (18-64 years)
Elderly (65 years and older)
Inclusion criteria
1. Age >18 years
2a. Diagnosis of SSc according to the 2013 EULAR-ACR classification criteria
for SSc,
2b. Diagnosis of VEDOSS, which is defined as the presence of RP, puffy fingers,
SSc specific autoantibodies and abnormal nailfold capillaroscopy.
3. Written informed consent
Exclusion criteria
1. Age < 18 years
2. Patients with diabetic cheiroarthropathy and Dupuytren*s disease
3. No written informed consent
Design
Study type :
Observational invasive
Masking :
Open (masking not used)
Control :
Uncontrolled
Primary purpose :
Diagnostic
Recruitment
NL
Recruitment status
:
Recruiting
Start date (anticipated) :
Enrollment :
200
Type :
Actual
Approved WMO
Date :
Application type :
First submission
Review commission :
METC NedMec
Approved WMO
Date :
Application type :
Amendment
Review commission :
METC NedMec
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL85445.041.23 |
