The aim of this study is to figure out which factors can predict the development of gout, in addition to hyperuricemia.
ID
Source
Brief title
Condition
- Joint disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
ROLE OF MSU CRYSTAL DEPOSITION IN TRANSITION FROM HYPERURICEMIA TO GOUT
- To determine whether ultrasound imaging evidence of MSU crystal deposition
predicts development of symptomatic gout (according to the 2015 ACR/EULAR
criteria [3]) over 5 years, in people who already have a high risk of gout due
to elevated serum urate concentrations (>=8 mg/dL).
- To describe the time-course for the development of gout over 5 years in
people at risk of gout with and without MSU deposition on ultrasound.
Secondary outcome
TRANSITION FROM HYPERURICEMIA TO DE NOVO MSU CRYSTAL DEPOSITION
- To determine factors that are associated with a higher risk of developing de
novo MSU crystal deposition on ultrasound over 5 years, in people who have
serum urate >=8 mg/dL.
TRANSITION TO SYMPTOMATIC GOUT AND ASSOCIATED COMORBIDITIES
- To identify risk factors (including clinical, genetic and biological) for the
development of gout in people who are at high risk of gout with serum urate >=8
mg/dL.
- To determine whether ultrasound evidence of MSU crystal deposition predicts
development of medical comorbidities including cardiovascular disease and
kidney disease
Baseline variables collected:
- demographic information as well as a physical exam including assessment of
body mass index, blood pressure and the presence of tenderness and swelling
using the 66/68 Tender Swollen Joint Count [5] and assessment for the absence
of subcutaneous tophi.
- Assessment of clinical risk factors, including exercise habits, consumption
of sugar-sweetened beverages, fruit and alcohol, smoking history and family
history of gout. I
- In addition, medications and comorbidities (including those required for the
gout-modified-Rheumatic Diseases Comorbidity Index (mRDCI) [6, 7]) will also be
collected.
- Health related quality of life (using the EuroQoL questionnaire [8]),
hyperuricemia-related illness perception (using the Brief Hyperuricemia
Perceptions Questionnaire (BIPQ) [9], beliefs about medicines (using the
Beliefs about Medicines Questionnaire) [10]
- body pain and foot pain over the past week using a 100 mm pain visual
analogue scales (VAS), activity limitation using the Health Assessment
Questionnaire - II (HAQ-II) [11] and foot-related pain and disability using the
Manchester Foot Pain and Disability Index (MFPDI) [12] will be assessed.
- Laboratory tests: creatinine and C-reactive protein (CRP), serum urate,
IL-1β.
- For those participants who agree to genetic testing, candidate gene analysis
for the progression from asymptomatic hyperuricemia to gout will include ABCG2,
TLR4, IL1B and PPARGC1B.
Background summary
From cross-sectional studies it is known that 17% to 86% of people with
apparently asymptomatic hyperuricemia have ultrasound imaging evidence of
monosodium urate (MSU) crystal deposition. These observations suggests that
this deposition constitutes the first stage of the clinical syndrome of gout,
which has led to a revised model of disease progression and staging. This
models proposes a linear progression from asymptomatic hyperuricaemia without
deposition, to asymptomatic hyperuricaemia with deposition, to symptomatic
disease. However, no longitudinal studies have been undertaken to establish
whether such imaging findings are necessary preconditions for the development
of gout nor what pathological mechanisms are responsible for the transition
from asymptomatic crystal deposition to gout, nor what mechanisms are involved
in the transition from hyperuricemia to de novo crystal deposition. Only a
prospective cohort study of persons at risk with careful, regular evaluation
can answer such questions.
Study objective
The aim of this study is to figure out which factors can predict the
development of gout, in addition to hyperuricemia.
Study design
This is a 5 year prospective cohort study of people with hyperuricemia but no
clinical symptoms of gout
Study burden and risks
Nature and extent of the burden associated with participation
Participants will be asked to attend a study visit at the Sint Maartenskliniek
Nijmegen. The study visit will take up to 2 hours. A second longer visit will
take place 5 years later, or sooner, if a participant develops gout. At each
study visit we will ask to complete some questions about health, assess the
height and weight, examine the joints for tenderness and swelling, assess
walking, and ask participants to provide a urine sample and blood samples to
test the urate levels, creatinine (kidney function) and CRP (marker of
inflammation).
We will also ask participants to provide blood tests to be stored. It is up to
the participants whether they also agree to the blood samples being used to
look at DNA, the genetic code material found inside the blood. It has been
known for a long time that high urate levels and the development of gout are
partly genetic because of certain genes that we inherit from our parents. We
want to find out what these genes are, and how they cause the disease. If they
wish to participate in the genetic study we will ask to also complete a
separate Genetics Testing Consent Form.
At the study visits we will also perform ultrasound scans of the feet and knees
to check for any urate crystals. At the first visit we will also take an x-ray
of the feet to check the health of the bones and joints in the feet.
Over the 5 years between the two study visits we will regularly contact
participants by phone, text, mail or email to check with whether participants
have developed any new joint pain or swelling. If so, we may schedule them in
for a second longer study visit earlier, to assess whether or not this pain or
swelling is due to gout.
As part of this study, we will ask participants whether they agree to providing
us with the contact details of a family member and/or close friend(s) that we
can contact if they cannot be reached.
With their consent we also may contact the family doctor.
Risks and benefits associated with participation
This study will involve the sampling of blood. A blood sample taken may hurt a
little, and some people get a small bruise where the needle goes in.
Occasionally the needle hole can become infected, but this is very rare. Most
people have no problems.
This study involves radiation exposure from a foot x-ray which will take place
at the first of the two longer study visits. As part of everyday living,
everyone is exposed to a small amount of background radiation that comes from
soil, rocks, outer space and within the body itself. The radiation dose
participants will receive in this study is about the amount that people receive
over 1 day from background radiation. This radiation exposure is necessary for
us to obtain information about the health of the bones and joints. The risk
from this dose is small.
The ultrasound scans involve no radiation exposure. Ultrasound scanning is safe
and painless. Sound waves are used to obtain images of the joints. This
technology is the same as that used to scan a pregnant woman and has no known
side effects.
Hengstdal 3
Ubbergen 6574 NA
NL
Hengstdal 3
Ubbergen 6574 NA
NL
Listed location countries
Age
Inclusion criteria
• Current serum urate level of >=8 mg/dl
• No current or previous clinical symptoms of gout (including flares or
clinically apparent tophi)
• Aged between 18 and 80 years
• Able to provide informed consent, according to requirements of local
IRB/ethics committee
Exclusion criteria
• eGFR < 30 mL/min/1.73 m² or on renal replacement therapy
• Serious illness with poor prognosis less than 5 years
• Auto-immune inflammatory arthritis
• Plans to shift out of area in the next 5 years
• Previous synovial fluid analysis showing MSU crystals
• The presence of subcutaneous tophi
• Taking urate lowering therapy (e.g. allopurinol, probenecid, benzbromarone,
febuxostat), canakinumab, or colchicine.
• Elevated serum urate documented only at the time of an acute medical illness
Design
Recruitment
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 | NL75260.091.20 |