To asses the short and long term effect on pain and function and the safety of doxycycline in patients with mild to severe pain due to established knee OA.
ID
Source
Brief title
Condition
- Joint disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Percentage of the patients achieving clinical response on pain and function, as
defined by the OMERACT-OARSI set of responder criteria compared to placebo at
week 24
Secondary outcome
Percentage of the patients achieving clinical response on pain and function, as
defined by the OMERACT-OARSI knee OA response criteria at week 96.
Mean KOOS pain sumscores question 5 to 9, function sumscore question 1 to 17
and VAS patient Global Assessment compared between baseline, week 24 and week
96.
Safety (adverse events graded according to the CTC criteria)
The rate of JSN in the medial knee compartment at week 96 as assessed by the
Lequesne scoring method (21)
Background summary
Knee osteoarthritis (Knee OA) is a prevalent chronic disease characterized
by cartilage failure resulting in pain, stiffness and function loss.
Symptomatic treatments for knee OA include medical treatment with analgesics
(acetaminophen) and NSAIDs, paramedical treatment including occupational and
physical therapy, weight reduction, and eventually joint replacement. Although
NSAIDs have been extensively studied and used for OA, there are some important
drawbacks to consider like inefficacy and gastrointestinal and cardiovascular
safety issues and possibly increased progression of knee OA. Therefore the
search for a DMAOD with both symptomatic and structural effects has been
intensified in recent years.
Doxycycline is a tetracycline class antibiotic agent. Besides being an
antimicrobacterial agent, it is a metalloproteinase inhibitor and inhibits the
collagenase that splices collagen type IX that is present in articular
cartilage. Doxycycline has been studied in human OA in one clinical trial by
Brandt et al. Although effect on structural change has been shown for
doxycycline, whether it also modifies symptoms for osteoarthritis has not been
established yet. Side effects were mild and drop-out due to side effects was
rare (<5%).
A possible beneficial effect of doxycycline on pain and function in knee OA
would allow this drug to be introduced in the non-invasive treatment of knee OA
for both symptomatic and structural benefit. Because doxycycline is not
associated with the important adverse effects of NSAIDs like gastrointestinal
and cardiovascular morbidity and mortality this could be of high clinical
relevance. In addition, doxycycline can be expected to have a beneficial effect
on cartilage compared to the possible deleterious effect of NSAIDs on
cartilage.
Study objective
To asses the short and long term effect on pain and function and the safety of
doxycycline in patients with mild to severe pain due to established knee OA.
Study design
Randomized, double blind placebo controlled trial (24 weeks) with open
extension (96 weeks).
Intervention
Doxycycline monohydrate 2dd100mg or Placebo for 24 weeks, thereafter open label
doxycycline monohydrate 2dd100mg
Study burden and risks
The experienced burden for patients included in this study is low. The
intervention has been shown to be safe and has excellent tolerability. Patients
will be taking two pills daily, and will be expected to visit the hospital
every three months in the placebo phase and every six months in the open
extension phase (with telephonic consultation in between). The outcome measures
are widely accepted and short questionnaires, routine safety blood tests and
standard x-rays at three time points.
Possible benifits include symptomatical relief by doxycyclin and delayed
progression of asteoarthritis.
Hengstdal 3
6522JV
NL
Hengstdal 3
6522JV
NL
Listed location countries
Age
Inclusion criteria
· Knee OA (index knee) according to the 1986 proposed ACR classification tree using clinical and radiological criteria: knee pain (VAS > 40mm during > 50% of last month), the presence of osteophytes and one of the following: age >50, crepitus, or morning stiffness < 30 minutes.
· Kellgren Lawrence score II or III
· Criteria for mild to severe pain (KOOS pain sumscore question 5 to 9 > 100 in the index knee) must be fulfilled
· Ability to read and communicate well in Dutch.
Exclusion criteria
· Other rheumatic diseases like rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematodes or psoriatic arthritis.
· The presence of secondary OA including OA caused by orthopaedic problems (severe malalignment, trauma), ochronosis, acromegaly, calcium pyrophosphate deposition disease (CPPD), haemochromatosis.
· Severe functional problems related to diseases other than OA (functional class ARA IV)
· Cognitive deficits affecting the scoring processes.
· Severe OA (Kellgren Lawrence score IV)
· Ipsilateral hip prosthesis in situ.
· Contraindications for doxycycline use like allergy for tetracyclines and prior adequate treatment with doxycycline (>100mg for > 6 weeks for OA).
· Planned other major interventions within 24 weeks, including lower limb surgery and intensive multidisciplinary approaches.
· Recent intra-articular hyaluronic acid or corticosteroid application (<3 months) or surgery (<1 year) in the index knee.
· Recent participation in other study (< 3 months)
Design
Recruitment
Medical products/devices used
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 |
|---|---|
| EudraCT | EUCTR2007-001151-19-NL |
| CCMO | NL16884.091.07 |