Combination Antibiotic Treatment for Reactive Arthritis Caused by Chlamydia Bacteria

NCT ID: NCT00351273

Last Updated: 2018-11-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-05-31
• Study Completion Date: 2008-09-30

Brief Summary

Reactive arthritis, also known as Reiter's syndrome, is a form of arthritis that occurs as a reaction to an infection elsewhere in the body. It is characterized by inflammation of the joints, tendons, urogenital tract, and eyes. Pain and swelling in the knees, ankles, and feet are common. This study will determine the effectiveness of antibiotic therapy in treating people with chlamydia-induced reactive arthritis that has lasted for more than 6 months.

Detailed Description

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.

Conditions

Arthritis, Reactive; Reiter Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Azithromycin and Rifampin

Participants received Azithromycin and Rifampin

Group Type: ACTIVE_COMPARATOR

Azithromycin and Rifampin

Intervention Type: DRUG

Azithromycin 500mg daily for 5 days and then twice weekly; Rifampin 300mg daily (both for 6 months)

Doxycycline and Rifampin

Participants received Doxycycline and Rifampin

Group Type: ACTIVE_COMPARATOR

Doxycycline and Rifampin

Intervention Type: DRUG

doxycycline 100mg daily; rifampin 300mg daily (both for 6 months)

received placebo

Participants received placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Methylcellulose

Interventions

Doxycycline and Rifampin

doxycycline 100mg daily; rifampin 300mg daily (both for 6 months)

Intervention Type: DRUG

Azithromycin and Rifampin

Azithromycin 500mg daily for 5 days and then twice weekly; Rifampin 300mg daily (both for 6 months)

Intervention Type: DRUG

Placebo

Methylcellulose

Intervention Type: DRUG

Other Intervention Names

Atridox and Rifadin; Zithromax and Rifadin; Placebo effect

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

NIH

Sponsor Role: collaborator

University of South Florida

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John D. Carter, MD

Role: PRINCIPAL_INVESTIGATOR

University of South Florida

Locations

University of South Florida

Tampa, Florida, United States

Louisiana State University

New Orleans, Louisiana, United States

University of Toronto

Toronto, Ontario, Canada

Countries

United States; Canada

References

Carter JD, Valeriano J, Vasey FB. Doxycycline versus doxycycline and rifampin in undifferentiated spondyloarthropathy, with special reference to chlamydia-induced arthritis. A prospective, randomized 9-month comparison. J Rheumatol. 2004 Oct;31(10):1973-80.

Reference Type: BACKGROUND

PMID: 15468362 (View on PubMed)

Carter JD, Espinoza LR, Inman RD, Sneed KB, Ricca LR, Vasey FB, Valeriano J, Stanich JA, Oszust C, Gerard HC, Hudson AP. Combination antibiotics as a treatment for chronic Chlamydia-induced reactive arthritis: a double-blind, placebo-controlled, prospective trial. Arthritis Rheum. 2010 May;62(5):1298-307. doi: 10.1002/art.27394.

Reference Type: DERIVED

PMID: 20155838 (View on PubMed)

Other Identifiers

R21AR053646

Identifier Type: NIH

Identifier Source: secondary_id

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1R21AR053646-01

Identifier Type: NIH

Identifier Source: secondary_id

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R21AR053646

Identifier Type: NIH

Identifier Source: org_study_id

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