Low and High Dose Dextrose Prolotherapy in the Treatment of Lateral Epicondylitis

Study Overview
=================
Brief Summary
-----------------
Lateral epicondylitis (tennis elbow) is an enthesopathy seen in 1-2% of the population aged 30-65 years, which can occur in the lateral epicondyle origo of the extensor carpi radialis brevis and longus muscles, after frequently repetitive activities and can lead to limitations in the daily life activities of the patients. The diagnosis is made by anamnesis and clinical examination, cases that last more than 3 months are defined as chronic lateral epicondylitis. Treatment options are analgesics, non-steroidal anti-inflammatory drugs, hand-wrist splints, eccentric strengthening exercises for forearm muscles and wrist dorsiflexors, injection therapies, physical therapy agents such as therapeutic ultrasound, ESWT(extracorporeal shockwave therapy), low-level laser therapy, and surgery. Prolotherapy is a treatment method that is performed with repetitive injections of a small amount of irritant or sclerosing solutions such as hypertonic dextrose, phenol-glycerin-glucose, or sodium morrhuate and aims to activate the healing process by increasing the blood flow around the damaged tendinopathy or enthesopathy area with the effect of these solutions. Hypertonic dextrose solutions in concentrations ranging from 12.5-20% are frequently used in prolotherapy. Prolotherapy can be done with ultrasound guidance or by determining anatomical landmarks. The injection is applied to the annular ligament, lateral epicondyle, and supracondylar area where the forearm extensor muscles adhere. Injection side effects and complications are pain, bruising, muscle spasm, nerve or vessel damage at the injection site. Based on previous studies, the low dose of dextrose solutions (1%, 5%, and 10%) may have a similar effect with fewer side effects than higher concentrations of dextrose solutions (15%, 20%, 25%) and the low dose may have fewer cell damage. Thus, it may be possible to apply an effective treatment method with fewer side effects in the treatment of lateral epicondylitis. Also, in this study, the effect of inflammation created by injection of saline in one group and the inflammatory, proliferative and angiogenic effects of dextrose injected in other groups at different concentrations on the treatment outcome will be compared.

Detailed Description
-----------------
Lateral epicondylitis (tennis elbow) is an enthesopathy seen in 1-2% of the population aged 30-65 years, which can occur in the lateral epicondyle origo of the extensor carpi radialis brevis and longus muscles, after frequently repetitive activities and can lead to limitations in the daily life activities of the patients. The diagnosis is made by anamnesis and clinical examination, cases that last more than 3 months are defined as chronic lateral epicondylitis. Treatment options are analgesics, non-steroidal anti-inflammatory drugs, hand-wrist splints, eccentric strengthening exercises for forearm muscles and wrist dorsiflexors, injection therapies, physical therapy agents such as therapeutic ultrasound, ESWT(extracorporeal shockwave therapy), low-level laser therapy, and surgery. Prolotherapy is a treatment method that is performed with repetitive injections of a small amount of irritant or sclerosing solutions such as hypertonic dextrose, phenol-glycerin-glucose, or sodium morrhuate and aims to activate the healing process by increasing the blood flow around the damaged tendinopathy or enthesopathy area with the effect of these solutions. Hypertonic dextrose solutions in concentrations ranging from 12.5-20% are frequently used in prolotherapy. Dextrose is an ideal proliferant agent due to its ability to dissolve in water, exists in the blood chemically, and to led safely apply to more than one place. It is known that hypertonic dextrose solutions dehydrate the cells in the injection area, cause local tissue trauma, attracts granulocytes and macrophages to the damaged area, and triggers healing. Prolotherapy can be done with ultrasound guidance or by determining anatomical landmarks. The injection is applied to the annular ligament, lateral epicondyle, and supracondylar area where the forearm extensor muscles adhere. Injection side effects and complications are pain, bruising, muscle spasm, nerve or vessel damage at the injection site. Based on previous studies, the low dose of dextrose solutions (1%, 5%, and 10%) may have a similar effect with fewer side effects than higher concentrations of dextrose solutions (15%, 20%, 25%) and the low dose may have fewer cell damage. Thus, it may be possible to apply an effective treatment method with fewer side effects in the treatment of lateral epicondylitis. Also, in this study, the effect of inflammation created by injection of saline in one group and the inflammatory, proliferative and angiogenic effects of dextrose injected in other groups at different concentrations on the treatment outcome will be compared.

Official Title
-----------------
Is Low Dose Dextrose Prolotherapy as Effective as High Dose Dextrose Prolotherapy in the Treatment of Lateral Epicondylitis?- A Double Blind- Ultrasound Guided- Randomized Controlled Study

Conditions
-----------------
Lateral Epicondylitis

Intervention / Treatment
-----------------
* Drug: Dextrose 5% in water
* Drug: Dextrose 15 % in Water
* Drug: Isotonic sodium chloride solution


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Those who admit Kirsehir Ahi Evran University Hospital and is diagnosed with lateral epicondylitis, Participants with unilateral or bilateral lateral epicondylitis and pain and functional limitations due to this condition, who can read and write in Turkish, participant's admission participating in the study, participants who do not have exclusion criteria, Exclusion Criteria: receiving any injection therapy to the elbow area in the last 3 months, participants with complaints less than 3 months(acute lateral epicondylitis) previously surgery on the elbow area, having a history of acute trauma or fracture in the elbow area, have local dermatological problems, have a local infection in the treatment area, those who are allergic to dextrose, with coagulation disorders or using anticoagulant drugs, with an autoimmune disease, with type 1 or type 2 diabetes mellitus, have unregulated hypertension, have immune dysfunction, with malignancy or diagnosed with a malignancy in the last 5 years, pregnancy or lactation, having cervical radiculopathy in the same extremity, with cognitive dysfunction, patients with paralysis in the same extremity, lack of cooperation due to cognitive impairment, participant's refusal to participate in the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: low dose dextrose arm (5% dextrose)<br>Prolotherapy injection will be made with 5% dextrose solution for 3 sessions with 3 weeks intervals. 1ml solution will be given with 27 Gauge 1/2 inch needles in the sessions. Before the treatment, the examination and questionnaire data of the patient will be recorded. | Drug: Dextrose 5% in water<br>* low dose dextrose solution<br>* Other names: 5% dextrose solution;|
| Active Comparator: high dose dextrose arm (15% dextrose)<br>Prolotherapy injection will be made with 15% dextrose solution for 3 sessions with 3 weeks intervals. 1ml solution will be given with 27 Gauge 1/2 inch needles in the sessions. Before the treatment, the examination and questionnaire data of the patient will be recorded. | Drug: Dextrose 15 % in Water<br>* high dose dextrose solution<br>* Other names: 15%dextrose solution;|
| Active Comparator: Isotonic saline arm (0.9% NaCl)<br>Prolotherapy injection will be made with isotonic saline for 3 sessions with 3 weeks intervals. 1ml solution will be given with 27 Gauge 1/2 inch needles in the sessions. Before the treatment, the examination and questionnaire data of the patient will be recorded. | Drug: Isotonic sodium chloride solution<br>* isotonic saline solution<br>* Other names: 0.9% NaCl solution;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the effect of prolotherapy injection on hand grip strength. | Evaluation of the effect of prolotherapy injection on hand grip strength Hand grip strength will be measured with Hand-Dynamometer, before injection treatment (pre-intervention), at the 3rd week (2nd session of treatment) and after the injection treatment (12th week). | Change of the hand grip strength at baseline, 3 weeks and after the injection treatment (12th week). | 
| Evaluation of elbow pain that develops at rest and movement before, during and after injection treatment. | Elbow pain at rest and movement will be assessed by Visual Analogue Scale, before injection treatment (pre-intervention), at the 3rd week (2nd session of treatment) and after the injection treatment (12th week). | Change in elbow pain at baseline, 3 weeks and after the injection treatment (12th week). | 
| Evaluation of elbow pain threshold, before, during and after injection treatment. | Elbow pain threshold will be assessed by Pain Algometer, before injection treatment (pre-intervention), at the 3rd week (2nd session of treatment) and after the injection treatment (12th week). | Change in elbow pain threshold at baseline, 3 weeks and after the injection treatment (12th week). | 
| Assessment of the effect of elbow pain on daily life activities. | Daily life activities will be measured with Quick-DASH(Disabilities of Arm, Shoulder and Hand) Questionnaire, before injection treatment (pre-intervention), at the 3rd week (2nd session of treatment) and after the injection treatment (12th week). | Change of the effect of elbow pain on daily life activities at baseline, 3 weeks and after the injection treatment (12th week). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the clinical improvement. | Clinical improvement of the patients will be evaluated subjectively with the Global Disease Assessment Questionnaire, before injection treatment (pre-intervention), at the 3rd week (2nd session of treatment) and after the injection treatment (12th week). | week 3 and 12 | 
| Evaluation of the injection side effects and complications. | Side effects and complications that may occur after injection treatments will be evaluated and compared between groups. | 12 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
prolotherapy, dextrose prolotherapy, tennis elbow, chronic lateral epicondylitis, dextrose therapy