Managing Chronic Tendon Pain by Metformin

June 2, 2026 updated by: James Wang

Managing Chronic Tendon Pain by Repurposing Metformin

The purpose of the current exploratory clinical trial is to determine the effect of oral ingestion of metformin (OIM) in non-diabetic patients with chronic Achilles tendon pain. The trial has two aims; 1) to assess the effects of OIM treatment on tendon pain, and 2) to determine the effects of OIM capsules on tendon healing and repair. Twenty participants will be treated with metformin capsules for 16 weeks combined with a home exercise program. A comparison group of 20 participants will be treated with placebo tablets along with home exercise program.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a blinded and randomized controlled trial that focuses on the treatment effects of metformin (Met) on chronic tendon pain, healing, and repair in midportion Achilles tendinopathy. We will include a total 40 patients randomly divided into two equal groups:

Group 1: Home Exercise Program + Placebo as a control group

Group 2: Home Exercise Program + Oral Ingestion of Metformin

Patients in group 1 will receive placebo capsules,1 capsule (500 mg) daily for week one, 2 capsules (1,000 mg) daily for week two, 3 capsules daily for week 3 (1,500 mg), and 4 capsules daily (2,000 mg) for weeks 4-16. Patients in group 2 will receive metformin capsules,1 capsule (500 mg) daily for week one, 2 capsules (1,000 mg) daily for week two, 3 capsules daily for week 3 (1,500 mg), and 4 capsules daily (2,000 mg) for weeks 4-16. All patients will participate in a home exercise program through MedBridge, a HIPAA-compliant participant portal currently used by physical therapists at University of Pittsburgh Medical Center. There are 3 visits for this study. Visits include a Screening/Baseline visit, week 4 and week 16 visit. During each visit, participants will answer questions, complete functional testing, and undergo an ultrasound of the Achilles Tendon.

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Willing and able to provide informed consent for participation
  • Clinical diagnosis of Achilles tendinopathy
  • Pain disability index score of between 20 - 70 points (0-100 scale VISA-A)
  • Sonopalpation tenderness with tendon thickening and/or loss of fibrillary architecture.
  • Ability to read, speak, and understand English

Exclusion Criteria:

  • Any intervention (corticosteroids or other orthobiologic intervention as injection) to targeted tissue within the last 6 months.
  • Previous Achilles tendon surgery.
  • Known platelet abnormality or hematological disorder.
  • Presence of other conditions that might affect the functional scale of the indexed limb.
  • Unwillingness to be randomized.
  • Body Mass Index (BMI) greater than 30.
  • Occult tear in the indexed tendon.
  • Systemic inflammatory disease.
  • Use of fluoroquinolone in the past 6 months.
  • Subjects must not be pregnant or breastfeeding, or planning to become pregnant or breastfeed during the course of the trial
  • Chronic kidney disease (eGFR <60)
  • Diagnosis of diabetes mellitus or elevated HbA1c at screening (> 6.5)
  • Unable to take an oral medication in a non crushable pill form
  • Taking metformin presently or within the last 6 months
  • History of allergy to metformin
  • History of lactic acidosis or elevated lactate at screening (> 2.2)
  • Severe Hepatic dysfunction
  • Currently taking a diabetic medication such as sitagliptin, saxagliptin, linagliptin, alogliptin, sitagliptin with metformin
  • Currently taking a Carbonic anhydrase inhibitor such as topiramate, zonisamide, acetazolamide, dichlorphenamide, methazolamide
  • Currently taking cimetidine

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo Group, Placebo Capsules
Placebo Group (n=20) Week 1: One placebo capsule (500 mg) daily Week 2: Two placebo capsules (1,000 mg) daily Week 3: Three placebo capsules (1,500 mg) daily Week 4-16: Four placebo capsules (2,000 mg) daily
Drug: Placebo
500 mg capsules of placebo pills
Experimental: Treatment Group, Metformin Capsules
Treatment Group (n=20) Week 1: One metformin ER capsule (500 mg) daily Week 2: Two metformin (ER) capsules (1,000 mg) daily Week 3: Three metformin (ER) capsules (1,500 mg) daily Week 4-16: Four metformin (ER) capsules (2,000 mg) daily
Drug: Metformin
500 mg capsules of Metformin Extended Release
Other Names:
  • Glucophage
  • Glucophage XR
  • Metformin Extended Release
  • Metformin ER

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Victorian Institute of Sport Assessment - Achilles (VISA-A) Score
Time Frame: baseline, 4 weeks, 16 weeks
The VISA-A is a self-administered questionnaire that asks about Achilles tendon pain, function, and activity. Scores range from 0 to 100 with a low score indicating more severe pain.
baseline, 4 weeks, 16 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in VAS score
Time Frame: baseline, 4 weeks, 16 weeks
The VAS is a self-administered questionnaire that asks about pain. Scores range from 0 to 10 with a high score indicating more severe pain.
baseline, 4 weeks, 16 weeks
Change in tendon thickness
Time Frame: baseline, 4 weeks, 16 weeks
Images of the Achilles tendon in long axis will be acquired using B-mode ultrasound imaging. Maximum Achilles tendon thickness (mm) will be measured by a blinded investigator.
baseline, 4 weeks, 16 weeks
Change in tendon cross-sectional area
Time Frame: baseline, 4 weeks, 16 weeks
Images of the Achilles tendon in short axis will be acquired using B-mode ultrasound imaging. Maximum Achilles tendon cross-sectional area (mm^2) will be measured by a blinded investigator.
baseline, 4 weeks, 16 weeks
Change in tendon neovascularization
Time Frame: baseline, 4 weeks, 16 weeks

Achilles tendon neovascularization will be evaluated using the 5-point modified Ohberg scale:

0 - no vessels visible

  1. one vessel, mostly anterior to the tendon
  2. one or two vessels throughout the tendon
  3. three vessels throughout the tendon
  4. more than three vessels throughout the tendon
baseline, 4 weeks, 16 weeks
Change in tendon hypoechogenicity
Time Frame: baseline, 4 weeks, 16 weeks

Hypoechogenicity is indicative of disruption of the normal fibrillar structure of the Achilles tendon. Achilles tendon hypoechogenicity will be evaluated using a semi-quantitative 3-point scale:

0 - no hypoechogenicity

  1. - Heterogeneous echotexture with diffuse hypoechogenicity between fibrillar echoes and/or foci of discontinuity in collagen fibrillar echoes
  2. - Heterogeneous echotexture with discrete hypoechoic area/s of >1mm and/or presence of intrasubstance tears
baseline, 4 weeks, 16 weeks
Change in maximum number of heel raises
Time Frame: baseline, 4 weeks, 16 weeks
The subject will stand barefoot on a 10° incline board and perform heel raises at a rate of 30 Hz (2 seconds per repetition, pace provided by audible metronome), while keeping their knee straight. Subjects will be allowed to have 2 fingertips per hand at shoulder height against the wall for balance. Participants will stop when they are unable to perform any additional repetitions, or if they fail to maintain proper form. Number of repetitions will be recorded.
baseline, 4 weeks, 16 weeks
Change in heel raise height
Time Frame: baseline, 4 weeks, 16 weeks
The subject will stand barefoot on a 10° incline board and perform heel raises at a rate of 30 Hz (2 seconds per repetition, pace provided by audible metronome), while keeping their knee straight. Subjects will be allowed to have 2 fingertips per hand at shoulder height against the wall for balance. Participants will stop when they are unable to perform any additional repetitions, or if they fail to maintain proper form. Maximum height of heel rise achieved during repetitions will be measured using the Calf Raise App.
baseline, 4 weeks, 16 weeks
Change in heel raise work
Time Frame: baseline, 4 weeks, 16 weeks
The subject will stand barefoot on a 10° incline board and perform heel raises at a rate of 30 Hz (2 seconds per repetition, pace provided by audible metronome), while keeping their knee straight. Subjects will be allowed to have 2 fingertips per hand at shoulder height against the wall for balance. Participants will stop when they are unable to perform any additional repetitions, or if they fail to maintain proper form. Total work (body weight x total distance) will be measured using the Calf Raise App.
baseline, 4 weeks, 16 weeks
Change in counter movement jump height
Time Frame: baseline, 4 weeks, 16 weeks
Subjects will stand on a single leg with their hands behind their back, bend their knee as much as desired, and jump as high as possible from flat ground. Three trials will be performed. Jump height will be determined using the My Jump2 App and the highest jump height will be utilized in further analysis.
baseline, 4 weeks, 16 weeks
Change in drop counter movement jump height
Time Frame: baseline, 4 weeks, 16 weeks
Subjects will stand on a single leg on top of an 8" plyometric box, with their hands behind their back. They will be asked to "fall" down to the floor and then immediately jump as high as possible from flat ground. Three trials will be performed. Jump height will be analyzed using the My Jump2 App and the highest jump height will be utilized in further analysis.
baseline, 4 weeks, 16 weeks
Change in VAS score during hopping
Time Frame: baseline, 4 weeks, 16 weeks
Subjects will be asked to complete two 2 trials of 25 single leg hops at a natural cadence similar to jumping rope (~2 jumps/second). Subjects will be asked to rate their pain during the exercise using VAS (0-10).
baseline, 4 weeks, 16 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

James Wang

Collaborators

United States Department of Defense

Investigators

  • Principal Investigator: James H Wang, PhD, University of Pittsburgh

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 24, 2024

Primary Completion (Estimated)

August 31, 2026

Study Completion (Estimated)

September 30, 2026

Study Registration Dates

First Submitted

October 9, 2023

First Submitted That Met QC Criteria

October 19, 2023

First Posted (Actual)

October 25, 2023

Study Record Updates

Last Update Posted (Actual)

June 4, 2026

Last Update Submitted That Met QC Criteria

June 2, 2026

Last Verified

November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STUDY23040151
  • HT9425-23-1-0712 (Other Grant/Funding Number: DOD)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Data obtained through this study may be provided to qualified researchers. Data or samples shared will be coded, with no PHI included. Approval of the request and execution of all applicable agreements (i.e. a material transfer agreement) are prerequisites to the sharing of data with the requesting party.

IPD Sharing Time Frame

Data requests can be submitted starting 9 months after article publication and the data will be made accessible for up to 24 months. Extensions will be considered on a case-by-case basis.

IPD Sharing Access Criteria

Access to trial IPD can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement. For more information or to submit a request, please contact wanghc@pitt.edu

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

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.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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