Intra-articular Doxycycline: A Novel Treatment of Adhesive Capsulitis

NCT ID: NCT03479502

Last Updated: 2024-01-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-05
• Study Completion Date: 2022-02-08

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.

Conditions

Adhesive Capsulitis; Adhesive Capsulitis of Unspecified Shoulder; Frozen Shoulder

Study Design

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

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Methylprednisolone Injectable Product

Intervention Type: DRUG

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

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.

Group Type: ACTIVE_COMPARATOR

Doxycycline Injection

Intervention Type: DRUG

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

Interventions

Methylprednisolone Injectable Product

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

Intervention Type: DRUG

Doxycycline Injection

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

Intervention Type: DRUG

Other Intervention Names

Prednisone; Doxy

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Orthopedic Research and Education Foundation

OTHER

Sponsor Role: collaborator

Vanderbilt University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

John Kuhn

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

John E Kuhn, MD

Role: STUDY_DIRECTOR

Study Director

Locations

Vanderbilt Medical Center

Nashville, Tennessee, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 21167743 (View on PubMed)

Neviaser AS, Hannafin JA. Adhesive capsulitis: a review of current treatment. Am J Sports Med. 2010 Nov;38(11):2346-56. doi: 10.1177/0363546509348048. Epub 2010 Jan 28.

Reference Type: RESULT

PMID: 20110457 (View on PubMed)

Hannafin JA, Chiaia TA. Adhesive capsulitis. A treatment approach. Clin Orthop Relat Res. 2000 Mar;(372):95-109.

Reference Type: RESULT

PMID: 10738419 (View on PubMed)

Bunker TD, Boyd M, Gallacher S, Auckland CR, Kitson J, Smith CD. Association between Propionibacterium acnes and frozen shoulder: a pilot study. Shoulder Elbow. 2014 Oct;6(4):257-61. doi: 10.1177/1758573214533664. Epub 2014 May 27.

Reference Type: RESULT

PMID: 27582943 (View on PubMed)

Levy O, Iyer S, Atoun E, Peter N, Hous N, Cash D, Musa F, Narvani AA. Propionibacterium acnes: an underestimated etiology in the pathogenesis of osteoarthritis? J Shoulder Elbow Surg. 2013 Apr;22(4):505-11. doi: 10.1016/j.jse.2012.07.007. Epub 2012 Sep 13.

Reference Type: RESULT

PMID: 22981447 (View on PubMed)

Stirling A, Worthington T, Rafiq M, Lambert PA, Elliott TS. Association between sciatica and Propionibacterium acnes. Lancet. 2001 Jun 23;357(9273):2024-5. doi: 10.1016/S0140-6736(00)05109-6. No abstract available.

Reference Type: RESULT

PMID: 11438138 (View on PubMed)

Dodson CC, Craig EV, Cordasco FA, Dines DM, Dines JS, Dicarlo E, Brause BD, Warren RF. Propionibacterium acnes infection after shoulder arthroplasty: a diagnostic challenge. J Shoulder Elbow Surg. 2010 Mar;19(2):303-7. doi: 10.1016/j.jse.2009.07.065. Epub 2009 Nov 1.

Reference Type: RESULT

PMID: 19884021 (View on PubMed)

Athwal GS, Sperling JW, Rispoli DM, Cofield RH. Deep infection after rotator cuff repair. J Shoulder Elbow Surg. 2007 May-Jun;16(3):306-11. doi: 10.1016/j.jse.2006.05.013. Epub 2007 Feb 22.

Reference Type: RESULT

PMID: 17321157 (View on PubMed)

Millett PJ, Yen YM, Price CS, Horan MP, van der Meijden OA, Elser F. Propionibacterium acnes infection as an occult cause of postoperative shoulder pain: a case series. Clin Orthop Relat Res. 2011 Oct;469(10):2824-30. doi: 10.1007/s11999-011-1767-4. Epub 2011 Jan 15.

Reference Type: RESULT

PMID: 21240577 (View on PubMed)

Schneeberger AG, Yian E, Steens W. Injection-induced low-grade infection of the shoulder joint: preliminary results. Arch Orthop Trauma Surg. 2012 Oct;132(10):1387-92. doi: 10.1007/s00402-012-1562-z. Epub 2012 Jun 17.

Reference Type: RESULT

PMID: 22707212 (View on PubMed)

Rollason J, McDowell A, Albert HB, Barnard E, Worthington T, Hilton AC, Vernallis A, Patrick S, Elliott T, Lambert P. Genotypic and antimicrobial characterisation of Propionibacterium acnes isolates from surgically excised lumbar disc herniations. Biomed Res Int. 2013;2013:530382. doi: 10.1155/2013/530382. Epub 2013 Aug 28.

Reference Type: RESULT

PMID: 24066290 (View on PubMed)

Brandt KD, Mazzuca SA, Katz BP, Lane KA, Buckwalter KA, Yocum DE, Wolfe F, Schnitzer TJ, Moreland LW, Manzi S, Bradley JD, Sharma L, Oddis CV, Hugenberg ST, Heck LW. Effects of doxycycline on progression of osteoarthritis: results of a randomized, placebo-controlled, double-blind trial. Arthritis Rheum. 2005 Jul;52(7):2015-25. doi: 10.1002/art.21122.

Reference Type: RESULT

PMID: 15986343 (View on PubMed)

Aydin O, Korkusuz F, Korkusuz P, Tezcaner A, Bilgic E, Yaprakci V, Keskin D. In vitro and in vivo evaluation of doxycycline-chondroitin sulfate/PCLmicrospheres for intraarticular treatment of osteoarthritis. J Biomed Mater Res B Appl Biomater. 2015 Aug;103(6):1238-48. doi: 10.1002/jbm.b.33303. Epub 2014 Oct 28.

Reference Type: RESULT

PMID: 25350566 (View on PubMed)

Haerdi-Landerer MC, Suter MM, Steiner A. Intra-articular administration of doxycycline in calves. Am J Vet Res. 2007 Dec;68(12):1324-31. doi: 10.2460/ajvr.68.12.1324.

Reference Type: RESULT

PMID: 18052736 (View on PubMed)

Cylwik J, Kita K, Barwijuk-Machala M, Reszec J, Klimiuk P, Sierakowski S, Sulkowski S. The influence of doxycycline on articular cartilage in experimental osteoarthrosis induced by iodoacetate. Folia Morphol (Warsz). 2004 May;63(2):237-9.

Reference Type: RESULT

PMID: 15232785 (View on PubMed)

Bernal-Lagunas R, Aguilera-Soriano JL, Berges-Garcia A, Luna-Pizarro D, Perez-Hernandez E. Haemophilic arthropathy: the usefulness of intra-articular oxytetracycline (synoviorthesis) in the treatment of chronic synovitis in children. Haemophilia. 2011 Mar;17(2):296-9. doi: 10.1111/j.1365-2516.2010.02402.x. Epub 2010 Nov 11.

Reference Type: RESULT

PMID: 21070486 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

172011

Identifier Type: -

Identifier Source: org_study_id