Combination Antibiotic Treatment for Reactive Arthritis Caused by Chlamydia Bacteria

The initial infection that causes reactive arthritis is caused by one of two bacteria:
Chlamydia trachomatis, which is usually acquired through sexual contact, or Chlamydia
pneumoniae, which can cause respiratory infections. Most people recover fully from the
initial flare of arthritis symptoms. However, about 20% of people with reactive arthritis
experience long-lasting symptoms. In these individuals, the Chlamydia bacteria exist in a
persistent metabolically active state within the joint tissue, even years after the initial
exposure. The bacteria produce heat shock proteins (HSPs), which are thought to play a key
role in the chronic persistent state of Chlamydia and which may stimulate the immune
inflammatory response seen in reactive arthritis. This indicates the need for antimicrobial
therapy that can reduce Chlamydia's HSP production and block its metabolism. The purpose of
this study is to determine the effectiveness of long-term combination antibiotic therapy in
treating people with chronic reactive arthritis. The study will use two different
combinations of common antibiotics: doxycycline paired with rifampin and azithromycin paired
with rifampin.

This study will entail 6 months of treatment followed by 3 months of follow-up. After
screening, eligible participants will be randomly assigned to one of three treatment groups:
rifampin once a day plus doxycycline twice a day; rifampin once a day plus azithromycin once
a day for 5 days, then twice weekly; or placebo. Study visits will occur at baseline and
Months 1, 3, 6, and 9. At all visits, participants will undergo an interview, a physical
examination, and blood collection. They will also complete a questionnaire related to their
symptoms and functional status. At screening and Month 6, a synovial biopsy may be performed.
This will involve taking a sample of the tissue that lines the joints.

Inclusion Criteria:

- Meet the following European Spondyloarthropathy Study Group Criteria:

1. inflammatory spinal pain OR

2. synovitis AND

3. one or more of the following:

1. positive family history

2. urethritis or cervicitis within 1 month prior to onset of arthritis

3. buttock pain

4. enthesopathy

5. sacroiliitis

- Disease duration of at least 6 months

- Negative pregnancy test at study baseline and willing to use an effective method of
contraception other than combined oral contraceptives for the duration of the study
(for women of childbearing age)

Exclusion Criteria:

- Sensitivity or history of allergic reaction to rifampin, doxycycline, or azithromycin

- Currently taking any medications that may interact with the study medications,
specifically rifampin

- Liver transaminases greater than or equal to two times the normal level

- Significant abnormalities in the complete blood count (CBC)

- Pregnant

- Current psoriasis

- Diagnosis of inflammatory bowel disease

- Diagnosis of ankylosing spondylitis

- Previous prolonged exposure to antibiotics (more than 2 weeks) as a potential
treatment for reactive arthritis