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Managing Chronic Tendon Pain by Metformin

Primary Purpose

Tendinopathy, Chronic Pain, Achilles Tendinopathy

Status
Not yet recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Metformin
Placebo
Sponsored by
James Wang
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Tendinopathy focused on measuring Achilles Tendon, Metformin, Achilles Tendinopathy, Chronic Pain

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Pittsburgh

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo Group, Placebo Capsules

Treatment Group, Metformin Capsules

Arm Description

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

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

Outcomes

Primary Outcome Measures

Change in Victorian Institute of Sport Assessment - Achilles (VISA-A) Score
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.

Secondary Outcome Measures

Change in VAS score
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.
Change in tendon thickness
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.
Change in tendon cross-sectional area
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.
Change in tendon neovascularization
Achilles tendon neovascularization will be evaluated using the 5-point modified Ohberg scale: 0 - no vessels visible one vessel, mostly anterior to the tendon one or two vessels throughout the tendon three vessels throughout the tendon more than three vessels throughout the tendon
Change in tendon hypoechogenicity
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 - Heterogeneous echotexture with diffuse hypoechogenicity between fibrillar echoes and/or foci of discontinuity in collagen fibrillar echoes - Heterogeneous echotexture with discrete hypoechoic area/s of >1mm and/or presence of intrasubstance tears
Change in maximum number of heel raises
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.
Change in heel raise height
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.
Change in heel raise work
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.
Change in counter movement jump height
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.
Change in drop counter movement jump height
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.
Change in VAS score during hopping
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).

Full Information

First Posted
October 9, 2023
Last Updated
October 19, 2023
Sponsor
James Wang
Collaborators
United States Department of Defense
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1. Study Identification

Unique Protocol Identification Number
NCT06100822
Brief Title
Managing Chronic Tendon Pain by Metformin
Official Title
Managing Chronic Tendon Pain by Repurposing Metformin
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 2023 (Anticipated)
Primary Completion Date
February 2025 (Anticipated)
Study Completion Date
April 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
James Wang
Collaborators
United States Department of Defense

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tendinopathy, Chronic Pain, Achilles Tendinopathy
Keywords
Achilles Tendon, Metformin, Achilles Tendinopathy, Chronic Pain

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Placebo Group, Placebo Capsules
Arm Type
Placebo Comparator
Arm Description
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
Arm Title
Treatment Group, Metformin Capsules
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Metformin
Other Intervention Name(s)
Glucophage, Glucophage XR, Metformin Extended Release, Metformin ER
Intervention Description
500 mg capsules of Metformin Extended Release
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
500 mg capsules of placebo pills
Primary Outcome Measure Information:
Title
Change in Victorian Institute of Sport Assessment - Achilles (VISA-A) Score
Description
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.
Time Frame
baseline, 4 weeks, 16 weeks
Secondary Outcome Measure Information:
Title
Change in VAS score
Description
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.
Time Frame
baseline, 4 weeks, 16 weeks
Title
Change in tendon thickness
Description
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.
Time Frame
baseline, 4 weeks, 16 weeks
Title
Change in tendon cross-sectional area
Description
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.
Time Frame
baseline, 4 weeks, 16 weeks
Title
Change in tendon neovascularization
Description
Achilles tendon neovascularization will be evaluated using the 5-point modified Ohberg scale: 0 - no vessels visible one vessel, mostly anterior to the tendon one or two vessels throughout the tendon three vessels throughout the tendon more than three vessels throughout the tendon
Time Frame
baseline, 4 weeks, 16 weeks
Title
Change in tendon hypoechogenicity
Description
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 - Heterogeneous echotexture with diffuse hypoechogenicity between fibrillar echoes and/or foci of discontinuity in collagen fibrillar echoes - Heterogeneous echotexture with discrete hypoechoic area/s of >1mm and/or presence of intrasubstance tears
Time Frame
baseline, 4 weeks, 16 weeks
Title
Change in maximum number of heel raises
Description
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.
Time Frame
baseline, 4 weeks, 16 weeks
Title
Change in heel raise height
Description
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.
Time Frame
baseline, 4 weeks, 16 weeks
Title
Change in heel raise work
Description
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.
Time Frame
baseline, 4 weeks, 16 weeks
Title
Change in counter movement jump height
Description
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.
Time Frame
baseline, 4 weeks, 16 weeks
Title
Change in drop counter movement jump height
Description
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.
Time Frame
baseline, 4 weeks, 16 weeks
Title
Change in VAS score during hopping
Description
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).
Time Frame
baseline, 4 weeks, 16 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
James H Wang, PhD
Phone
4126489102
Email
wanghc@pitt.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
James H Wang, PhD
Organizational Affiliation
University of Pittsburgh
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jessica Eldridge
Email
eldridgejl@upmc.edu

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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

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Managing Chronic Tendon Pain by Metformin

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