Clinical trial NCT03479502: Intra-articular Doxycycline: A Novel Treatment of Adhesive Capsulitis
Official title: Intra-articular Doxycycline: A Novel Treatment of Adhesive Capsulitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Adhesive Capsulitis
Adhesive Capsulitis of Unspecified Shoulder
Frozen Shoulder
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
Collaborators: name: Orthopedic Research and Education Foundation
First posted: 2018-03-27
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients meeting the inclusion criteria will be randomized into either the control group of intra-articular injection of 40mg Methylprednisolone once every 2 two weeks for 4 weeks (day 1, week 2, week 4) or the experimental group of intraarticular injection of 50 mg doxycycline once every 2 two weeks for 4 weeks (day 1, week 2, week 4), with 20 patients in each group. Injections will be administered by the treating physician. The Vanderbilt Investigational Pharmacy will provide the doxycycline and the steroid solutions and will be in charge of patient randomization.
Primary purpose: TREATMENT

Brief summary: We will recruit a total of 40 patients from the Vanderbilt Sports Medicine Clinics who have been diagnosed with adhesive capsulitis and have not undergone any previous treatment. The 40 patients will be randomized, with 20 in the control group of 3 intra-articular injections of 40mg Methylprednisolone spaced every two weeks, and 20 in the experimental group of 3 intra-articular injection of 50mg doxycycline spaced every two weeks. Both groups will begin a standardized physical therapy program within a pain-free range of motion 4 weeks after the initiation of treatment. We will prospectively follow patients for one year, with follow-up at 6 weeks, 12 weeks, 6 months, and 12 months after the initiation of treatment.

Outcomes will be measured using the American Shoulder and Elbow Score (ASES) and objective measurements of shoulder range of motion, which will be collected by the treating physician. Both the patients and physicians participating in the study will be blinded.

Detailed description: Adhesive capsulitis, also known as frozen shoulder, is a common condition of the shoulder joint affecting 2-5% of the adult population and characterized by progressive, painful loss of both passive and active range of motion of shoulder \[1,2\]. Individuals affected by this condition find it increasingly difficult to perform activities of daily living that require overhead movement or rotation of the affected shoulder. The natural history of frozen shoulder follows a predictable progression of symptoms, lasting from 9-24 months before complete resolution, and results in significant loss of productivity and quality of life for those affected \[3\]. Despite the significant number of patients affected by adhesive capsulitis and the extensive literature focused on the progression and natural history of the condition, the true underlying etiology remains poorly understood. In light of this poor understanding of the condition, it is not surprising that a number of conservative and invasive modalities exist as accepted treatments. These include non-steroidal anti-inflammatory drugs (NSAIDS), oral steroids, intra-articular steroid injections, Physical Therapy (PT), and benign neglect as well as more invasive treatments such as hydroxylation, manipulation under anesthesia, and arthroscopic capsular release \[2\]. These treatments have all be shown to have short-term benefit in pain relief, but none have proven to be superior nor alter the long-term natural history of adhesive capsulitis.

Over the past decade, however, there has been a growing body of literature suggesting that Propionibacterium acnes infection may play a significant role in a variety of pathological conditions affecting the native shoulder, most notably frozen shoulder \[4,5\]. Our goal is to employ a treatment strategy focused on eradicating P acnes infection as a conservative treatment of adhesive capsulitis. Through this project, we aim to complete a prospective randomized pilot study to examine the hypothesis that administration of intra-articular antibiotics effective against P acnes will prove to be a superior treatment of adhesive capsulitis as compared to current gold standard of intraarticular steroid injection.

Eligibility criteria: Inclusion Criteria:

* 18 years of age and older,
* diagnosis of stage II adhesive capsulitis as determined by clinical examination of the treating physician, and
* absence of abnormal findings on X-ray.

Exclusion Criteria:

* allergy to Doxycycline or Methylprednisolone,
* pregnancy,
* diagnosis,
* Inflammatory arthritis or diabetes,
* secondary adhesive capsulitis (history of significant trauma, rotator cuff tear injury, stroke)
* evidence of arthritis on x-ray,
* current infectious disease, and
* any previous treatment for the for adhesive capsulitis of the affected shoulder.

Primary outcomes:
measure: Change in American Shoulder and Elbow Score (ASES)
timeFrame: Baseline and 12 months
measure: Change in Range of Motion(ROM) Measurements
timeFrame: Baseline and 12 months
Secondary outcomes:
measure: Number of Medical Co-morbidities
timeFrame: Baseline
measure: Duration of Symptoms
timeFrame: Baseline
measure: Changes in Pain
timeFrame: Baseline
measure: Pain With Sitting
timeFrame: Baseline
measure: Stiffness
timeFrame: Baseline
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt Medical Center
state: Tennessee
Study officials:
affiliation: Study Director
name: John E Kuhn, MD
role: STUDY_DIRECTOR
References:
citation: Hsu JE, Anakwenze OA, Warrender WJ, Abboud JA. Current review of adhesive capsulitis. J Shoulder Elbow Surg. 2011 Apr;20(3):502-14. doi: 10.1016/j.jse.2010.08.023. Epub 2010 Dec 16. No abstract available.
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