DOXY: Intra-articular Doxycycline: A Novel Treatment of Adhesive Capsulitis

Sponsor

Vanderbilt University Medical Center (Other)

Overall Status

Terminated

CT.gov ID

NCT03479502

Collaborator

Orthopedic Research and Education Foundation (Other)

Enrollment

Location

Arms

49.1

Actual Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Adhesive Capsulitis Adhesive Capsulitis of Unspecified Shoulder Frozen Shoulder	Drug: Methylprednisolone Injectable Product Drug: Doxycycline Injection	Phase 4

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

1 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

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.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.

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Masking Description:

Double Blind Masking

Primary Purpose:

Treatment

Official Title:

Intra-articular Doxycycline: A Novel Treatment of Adhesive Capsulitis

Actual Study Start Date :

Jan 5, 2018

Actual Primary Completion Date :

Feb 8, 2022

Actual Study Completion Date :

Feb 8, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Methylprednisolone 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) with 20 patients in each group. Injections will be administered by the treating physician.	Drug: Methylprednisolone Injectable Product 3 intra-articular injections of Methylprednisolone Injectable Product spaced every two weeks Other Names: Prednisone
Active Comparator: Doxycycline Patients meeting the inclusion criteria will be randomized 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.	Drug: Doxycycline Injection 3 intra-articular injections of Doxycycline Injection spaced every two weeks Other Names: Doxy

Arm

Intervention/Treatment

Active Comparator: Methylprednisolone

Drug: Methylprednisolone Injectable Product

3 intra-articular injections of Methylprednisolone Injectable Product spaced every two weeks

Other Names:

Prednisone

Active Comparator: Doxycycline

Patients meeting the inclusion criteria will be randomized 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.

Drug: Doxycycline Injection

3 intra-articular injections of Doxycycline Injection spaced every two weeks

Other Names:

Doxy

Outcome Measures

Primary Outcome Measures

Change in American Shoulder and Elbow Score (ASES) [Baseline and 12 months]
The ASES questionnaire was developed to provide a standardized method for evaluating shoulder function and has been validated in patients with any array of shoulder pathologies
Change in Range of motion(ROM) measurements [Baseline and 12 months]
The ROM measurements will include forward flexion, abduction, external rotation at the side and at 90 degrees abduction, and internal rotation at the side and at 90 degrees abduction recorded by the treating physician at follow up visits

Secondary Outcome Measures

number of medical co-morbidities [Baseline]
number of medical co-morbidities per participant
Duration of symptoms [Baseline]
Length of time participants have experienced shoulder symptoms
Changes in Pain [Baseline]
Number of participants with current dominant symptom and/or dominant symptom with disease onset
Pain with sitting [Baseline]
Number of patients that have pain while sitting or have ever had pain while sitting will be recorded using patient-reported survey and review of the patient's electronic medical record in Epic.
Stiffness [Baseline]
Number of participants with current dominant symptom and/or dominant symptom with disease onset

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.