Doxycycline for Elbow Tendinopathy

Evaluating the Feasibility of Subantimicrobial-dose Doxycycline for Elbow Tendinopathy

To evaluate the feasibility of subantimicrobial -dose (SD) doxycycline to improve outcomes of nonsurgical management of elbow tendinopathy via matrix metalloproteinase (MMP) inhibition as well as evaluate if participants will be compliant to with prescribed medication and exercise treatment. Our working hypothesis is that patients with elbow tendinopathy will be receptive to treatment with SD-doxycycline and compliant with the prescribed treatment.

Study Overview

• Status: Active, not recruiting
• Conditions: Lateral Epicondylitis; Lateral Epicondylitis, Unspecified Elbow; Lateral Epicondylitis, Left Elbow; Lateral Epicondylitis, Right Elbow; Lateral Epicondylitis (Tennis Elbow) Bilateral; Medial Epicondylitis; Medial Epicondylitis, Right Elbow; Medial Epicondylitis, Left Elbow
• Intervention / Treatment: Drug: Doxycycline Hyclate 20 MG

Detailed Description

: elbow tendinopathy is a common condition among athletes and the general population. It can result in significant disability and time loss from work. Despite traditional nonsurgical treatment, symptoms often persist for more than 6 months. Second-line treatments, such as platelet rich plasma injections and extracorporeal shock wave therapy, have limited evidence and are often cost-prohibitive. There remains a need for additional cost-effective nonsurgical treatment for elbow tendinopathy.

Purpose: To evaluate the feasibility of subantimicrobial -dose (SD) doxycycline to improve outcomes of nonsurgical management of elbow tendinopathy via matrix metalloproteinase (MMP) inhibition as well as evaluate if participants will be compliant to with prescribed medication and exercise treatment. Our working hypothesis is that patients with elbow tendinopathy will be receptive to treatment with SD-doxycycline and compliant with the prescribed treatment.

Methods: This study will enroll 25 otherwise healthy males and females ages 18 and up with ≥ 6 weeks of symptomatic lateral or medial elbow tendinopathy. Subjects will receive doxycycline 20 mg BID (twice a day) for 12 weeks. Usual care will also be provided with a home exercise program and a counterforce brace. The proportion of eligible patients who elect to participate in the study will be tracked as a measure of receptiveness. Biweekly logs will be collected to monitor for treatment side effects and track compliance. Patient reported outcomes will include quick Disabilities of the Arm Shoulder and Hand score (qDASH) and Patient-Rated Tennis Elbow Evaluation (PRTEE) at baseline, 4, 8, and 12 weeks. Ultrasound tendinopathy grade and grip strength will be measured at baseline and 12 weeks. Blood will be drawn to assess MMP activity and collagen production/connective tissue anabolism at baseline and 12 weeks.

Significance: This study will provide the necessary data to design a phase two-a trial of a safe, low-cost adjuvant treatment for a common condition treated by sports medicine and primary care physicians. If found to be beneficial for elbow tendinopathy, SD-doxycycline may have utility in other types of tendinopathy as well.

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Brianna I Quijano, MS; Phone Number: 845-705-7685; Email: quijanob@hss.edu
• Study Contact Backup: Name: Jessica Rios; Phone Number: (212) 774-7321; Email: riosj@hss.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Hospital for Special Surgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Males and females ages of 18 and up
• Atraumatic unilateral elbow pain of ≥ 6 weeks duration
• Diagnosed clinically as lateral or medial elbow tendinopathy
• Activity-related lateral or medial elbow pain
• Tenderness of the lateral or medial epicondyle
• Pain with gripping and/or resisted wrist extension with the elbow extended
• Pain with passive wrist flexion and finger with the elbow extended
• Internet access to complete electronic surveys

Exclusion Criteria:

• Prior surgery of the affected elbow
• Prior injection of the affected lateral or medial epicondyle or extensor tendons
• Prior extracorporeal shockwave therapy to the affected elbow
• Suspicion for radial tunnel syndrome (tenderness distal to the lateral epicondyle in the area of the supinator muscle dorsally, pain with resisted supination with the elbow extended, and/or weakness of the extensor digitorum communis)
• Separate upper extremity injury or condition that would interfere with full participation in the home exercise program
• Fluoroquinolone-associated tendinopathy
• Ligamentous laxity on exam
• Evidence of osteoarthritis or osteochondral lesion on radiographs
• Autoimmune condition
• Pregnant, intend to become pregnant, or breastfeeding
• Premenopausal women who are not using contraception
• Allergy to doxycycline or other tetracyclines
• Current esophagitis or peptic ulcer disease
• Current use of medication for which there is a drug interaction with doxycycline
• Who do not speak English

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SD-doxycycline group; 12 weeks SD-doxycycline: doxycycline hyclate 20 mg tablet by mouth twice daily	Drug: Doxycycline Hyclate 20 MG; Subjects will receive doxycycline 20 mg BID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primarily a feasibility study of SD-doxycycline as an adjunctive treatment for elbow tendinopathy (Compliance)	Compliance: At the end of the study, compliance will be calculated using the number of self-reported doses taken divided by the number of prescribed doses (twice daily x 7 days per week x 12 weeks = 168 doses).	12 weeks
Receptiveness	The number of patients who enroll in study divided by the number eligible patients minus the number of patients who decline due to reasons unrelated to the prescribed treatment, e.g., unable to return for second study visit. This will be measured at time of study recruitment.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical outcomes - qDASH	quick Disabilities of the Arm Shoulder and Hand score (by qDASH score) at baseline, 4, 8, and 12 weeks	12 weeks
Clinical outcomes - PRTEE	Patient-Rated Tennis Elbow Evaluation (by PRTEE test ) at baseline, 4, 8, and 12 weeks	12 weeks
Secondarily, clinical outcomes will be measured to provide preliminary data to power a future randomized controlled trial. (Ultrasound tendinopathy grade)	Ultrasound tendinopathy grade at baseline at 12 weeks - by ultrasound	12 weeks
Clinical outcomes - Grip strength	Grip strength at baseline and 12 weeks - measure by hand-held dynamometer	12 weeks
Clinical outcomes - MMP	Matrix metalloproteinase (MMP) inhibition activity and collagen production/connective tissue anabolism at baseline and 12 weeks - measure by blood test	12 weeks

Collaborators and Investigators

• Sponsor: Hospital for Special Surgery, New York
• Investigators: Principal Investigator: Brett G Toresdahl, MD, Hospital for Special Surgery, New York

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2020
• Primary Completion (Estimated): November 1, 2024
• Study Completion (Estimated): November 1, 2024

Study Registration Dates

• First Submitted: November 6, 2020
• First Submitted That Met QC Criteria: December 28, 2020
• First Posted (Actual): December 29, 2020

Study Record Updates

• Last Update Posted (Actual): December 13, 2023
• Last Update Submitted That Met QC Criteria: December 12, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Feasibility; efficacy
• Additional Relevant MeSH Terms: Wounds and Injuries; Musculoskeletal Diseases; Muscular Diseases; Tendon Injuries; Arm Injuries; Elbow Injuries; Tendinopathy; Tennis Elbow; Elbow Tendinopathy; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Doxycycline
• Other Study ID Numbers: 2020-1582

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All individual participant data collected during the trial after deidentification
• IPD Sharing Time Frame: Immediately following study publication. No end date.
• IPD Sharing Access Criteria: Any purpose
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes