Skip to content

Intra-articular Doxycycline: A Novel Treatment of Adhesive Capsulitis

Intra-articular Doxycycline: A Novel Treatment of Adhesive Capsulitis

Status
Completed
Phases
Phase 4
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT03479502
Acronym
DOXY
Enrollment
1
Registered
2018-03-27
Start date
2018-03-05
Completion date
2022-02-08
Last updated
2024-01-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Adhesive Capsulitis, Adhesive Capsulitis of Unspecified Shoulder, Frozen Shoulder

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.

Interventions

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

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

Sponsors

Orthopedic Research and Education Foundation
CollaboratorOTHER
Vanderbilt University Medical Center
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)

Masking description

Double Blind Masking

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.

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
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.

Design outcomes

Primary

MeasureTime frameDescription
Change in American Shoulder and Elbow Score (ASES)Baseline and 12 monthsThe American Shoulder and Elbow Score questionnaire was developed to provide a standardized method for evaluating shoulder function and has been validated in patients with any array of shoulder pathologies. ASES results are in the 0 to 100 range, where 0 indicates a worse shoulder condition and 100 indicates best shoulder condition, so the lower the score, the greater the level of shoulder disability. Transforming the pain and the ADLs domains into the final score relies on the following formulas: Pain = 5 x (10 - Score from question 7)
Change in Range of Motion(ROM) MeasurementsBaseline and 12 monthsThe 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

MeasureTime frameDescription
Changes in PainBaselineNumber of participants with current dominant symptom and/or dominant symptom with disease onset
Number of Medical Co-morbiditiesBaselinenumber of medical co-morbidities per participant
StiffnessBaselineNumber of participants with current dominant symptom and/or dominant symptom with disease onset
Pain With SittingBaselineNumber 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.
Duration of SymptomsBaselineLength of time participants have experienced shoulder symptoms

Countries

United States

Participant flow

Participants by arm

ArmCount
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. Methylprednisolone Injectable Product: 3 intra-articular injections of Methylprednisolone Injectable Product spaced every two weeks
1
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. Doxycycline Injection: 3 intra-articular injections of Doxycycline Injection spaced every two weeks
0
Total1

Baseline characteristics

CharacteristicMethylprednisoloneTotal
Age, Categorical
<=18 years
0 Participants0 Participants
Age, Categorical
>=65 years
0 Participants0 Participants
Age, Categorical
Between 18 and 65 years
1 Participants1 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants0 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
1 Participants1 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants
Region of Enrollment
United States
1 Participants1 Participants
Sex: Female, Male
Female
1 Participants1 Participants
Sex: Female, Male
Male
0 Participants0 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
0 / 10 / 0
other
Total, other adverse events
0 / 10 / 0
serious
Total, serious adverse events
0 / 10 / 0

Outcome results

Primary

Change in American Shoulder and Elbow Score (ASES)

The American Shoulder and Elbow Score questionnaire was developed to provide a standardized method for evaluating shoulder function and has been validated in patients with any array of shoulder pathologies. ASES results are in the 0 to 100 range, where 0 indicates a worse shoulder condition and 100 indicates best shoulder condition, so the lower the score, the greater the level of shoulder disability. Transforming the pain and the ADLs domains into the final score relies on the following formulas: Pain = 5 x (10 - Score from question 7)

Time frame: Baseline and 12 months

Population: 0 participants were analyzed due to the risk of de-identification with only 1 person enrolled.

Primary

Change in Range of Motion(ROM) Measurements

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

Time frame: Baseline and 12 months

Population: 0 participants were analyzed due to the risk of de identification with only 1 person enrolled.

Secondary

Changes in Pain

Number of participants with current dominant symptom and/or dominant symptom with disease onset

Time frame: Baseline

Population: 0 participants enrolled due to the risk of de identifying with only 1 person enrolled.

Secondary

Duration of Symptoms

Length of time participants have experienced shoulder symptoms

Time frame: Baseline

Population: 0 participants enrolled due to the risk of de identification with only 1 person enrolled.

Secondary

Number of Medical Co-morbidities

number of medical co-morbidities per participant

Time frame: Baseline

Population: 0 parrticipants were ananlyzed due to the risk of de identification with only person enrolled.

Secondary

Pain With Sitting

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.

Time frame: Baseline

Population: 0 participants enrolled due to the risk of de identifying with only 1 person enrolled.

Secondary

Stiffness

Number of participants with current dominant symptom and/or dominant symptom with disease onset

Time frame: Baseline

Population: 0 participants enrolled due to the risk of de identifying with only 1 person enrolled

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026