Clinical trial NCT06100822: Managing Chronic Tendon Pain by Metformin
Official title: Managing Chronic Tendon Pain by Repurposing Metformin
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Tendinopathy
Chronic Pain
Achilles Tendinopathy
Keywords: Achilles Tendon
Metformin
Achilles Tendinopathy
Chronic Pain
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
First posted: 2023-10-25
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change in Victorian Institute of Sport Assessment - Achilles (VISA-A) Score
timeFrame: baseline, 4 weeks, 16 weeks
Secondary outcomes:
measure: Change in VAS score
timeFrame: baseline, 4 weeks, 16 weeks
measure: Change in tendon thickness
timeFrame: baseline, 4 weeks, 16 weeks
measure: Change in tendon cross-sectional area
timeFrame: baseline, 4 weeks, 16 weeks
measure: Change in tendon neovascularization
timeFrame: baseline, 4 weeks, 16 weeks
measure: Change in tendon hypoechogenicity
timeFrame: baseline, 4 weeks, 16 weeks
measure: Change in maximum number of heel raises
timeFrame: baseline, 4 weeks, 16 weeks
measure: Change in heel raise height
timeFrame: baseline, 4 weeks, 16 weeks
measure: Change in heel raise work
timeFrame: baseline, 4 weeks, 16 weeks
measure: Change in counter movement jump height
timeFrame: baseline, 4 weeks, 16 weeks
measure: Change in drop counter movement jump height
timeFrame: baseline, 4 weeks, 16 weeks
measure: Change in VAS score during hopping
timeFrame: baseline, 4 weeks, 16 weeks
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: James H Wang, PhD
role: PRINCIPAL_INVESTIGATOR
References: