Prolotherapy Intervention in Patient With Frozen Shoulder

Frozen Shoulder Clinical Trial

Official title:

The Level of Matrix Metalloproteinase-1 (MMP-1), Tissue Inhibitor Matrix Metalloproteinase-1 (TIMP-1) After Prolotherapy Intervention and The Functional Outcome in Patient With Frozen Shoulder

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05131269
• Other study ID #: 0411211741
• Status: Completed
• Phase: Phase 4
• Start date: December 1, 2021
• Est. completion date: November 30, 2022

Study information

• Verified date: December 2022
• Source: Hasanuddin University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Introduction :

Prolotherapy is regenerative tissue therapy that is considered to be efficacious in reducing symptoms and morbidity of frozen shoulder, but only a few studies demonstrate the effect of prolotherapy at the biomolecular level, particularly the level of Matrix Metalloproteinase- I (MMP-1), Tissue Inhibitor Matrix Metalloproteinase (TIMP-1), as the biomarkers of cartilage repair.

Objective:

To determine the effect of prolotherapy on MMP-1, TIMP-1, and functional outcomes in frozen shoulder patients

Method:

a double-blind randomized controlled trial study involving participants who had been diagnosed with Frozen Shoulder. History taking, functional outcome assessment, MMP-1, and TIMP-1 were measured. The prolotherapy via intraarticular and extraarticular was performed four times, followed by the evaluation of functional outcome, MMP-1, and TIMP-1 at week 12

Alternative Hypothesis :

Prolotherapy will increase the MMP-1, TIMP-1 levels, and improve functional outcome among Frozen Shoulder patients

Description:

Design :

Double-blind randomized trial

Randomization :

Simple Randomization generated by an online randomizer

Sample Size :

Difference between two means of primary outcome where

1. mean difference (μ 1 - μ 2 ) = 0.47

2. pool variance = 0.09

3. Z 1-α/2 = 1.95 with type 1 error 5%

4. 1-β = 1.282 with power 90%. Yielding 16 patients for each arm

Detailed Intervention

1. Intervention group: Prolotherapy is given four times (Week 0, Week 2, Week 4, and Week 6)

2. Comparison group: Normal Saline is given four times with a timeframe similar to the intervention group

Injection location

1. Rotator Cuff muscles

2. Intraarticular glenohumeral joint

3. Subacromial bursa

4. long-heap of the biceps tendon

5. Acromioclavicular joint

Statistical analysis :

1. Descriptive statistic to elaborate baseline characteristic

2. Assuming the baseline characteristic between groups are similar, the independent t-test will be conducted to see the differences between group, whereas Mann Whitney will be performed for nonparametric data

3. Difference within-group (baseline and last day) will be measured by paired-t-test or Wilcoxon for non parametric scenario

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: November 30, 2022
• Est. primary completion date: May 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 35 Years to 70 Years

Eligibility

1. Inclusion Criteria

1. Age 35-70

2. Diagnosed with frozen shoulder

3. At least showing symptoms more than 3 months

2. Exclusion Criteria

1. Receiving other intraarticular injection

2. Taking Nonsteroid Antiinflammation drugs 1 week prior to intervention

3. Skin disorder around the injection site

4. Septic arthritis

Related Conditions & MeSH terms

• Bursitis
• Frozen Shoulder

Intervention

Drug:
• Dextrose 15 % in Water
A 15% dextrose solution is given to shoulder segments four times with 2 weeks interval (week 0,2,4, and 6)
• Normal Saline 20 mL Injection
A Normal Saline 0.9% is given to shoulder segments four times with 2 weeks interval (week 0,2,4, and 6)

Locations

Country	Name	City	State
Indonesia	Hasanuddin University, Faculty of Medicine	Makassar	South Sulawesi

Sponsors (1)

Lead Sponsor	Collaborator
Bumi Herman

Country where clinical trial is conducted

Indonesia, 

References & Publications (5)

Akcay S, Gurel Kandemir N, Kaya T, Dogan N, Eren M. Dextrose Prolotherapy Versus Normal Saline Injection for the Treatment of Lateral Epicondylopathy: A Randomized Controlled Trial. J Altern Complement Med. 2020 Dec;26(12):1159-1168. doi: 10.1089/acm.2020.0286. Epub 2020 Sep 28. — View Citation

Cho CH, Song KS, Kim BS, Kim DH, Lho YM. Biological Aspect of Pathophysiology for Frozen Shoulder. Biomed Res Int. 2018 May 24;2018:7274517. doi: 10.1155/2018/7274517. eCollection 2018. — View Citation

Distel LM, Best TM. Prolotherapy: a clinical review of its role in treating chronic musculoskeletal pain. PM R. 2011 Jun;3(6 Suppl 1):S78-81. doi: 10.1016/j.pmrj.2011.04.003. — View Citation

Lubis AM, Lubis VK. Matrix metalloproteinase, tissue inhibitor of metalloproteinase and transforming growth factor-beta 1 in frozen shoulder, and their changes as response to intensive stretching and supervised neglect exercise. J Orthop Sci. 2013 Jul;18(4):519-27. doi: 10.1007/s00776-013-0387-0. Epub 2013 Apr 19. — View Citation

Saltzman BM, Leroux T, Meyer MA, Basques BA, Chahal J, Bach BR Jr, Yanke AB, Cole BJ. The Therapeutic Effect of Intra-articular Normal Saline Injections for Knee Osteoarthritis: A Meta-analysis of Evidence Level 1 Studies. Am J Sports Med. 2017 Sep;45(11):2647-2653. doi: 10.1177/0363546516680607. Epub 2016 Dec 27. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Matrix Metalloproteinase 1 in Blood	Matrix Metalloproteinase 1 from whole blood measured using Enzyme-linked Immunoassay (ELISA). Mean difference between group will be assessed	changes of Matrix Metalloproteinase 1 value from baseline to week 6
Primary	Tissue Inhibitor Metalloproteinase 1 in Blood	Tissue Inhibitor Metalloproteinase 1 from whole blood measured using Enzyme-linked Immunoassay (ELISA). Mean difference between group will be assessed	changes of Tissue Inhibitor Metalloproteinase 1 value from baseline to week 6
Secondary	The Functional Outcome of the Shoulder	The functional outcome is measured using the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire where the patient were asked to do simple task involving the arm, shoulder and hand and also the assessment of additional symptoms and impact to daily life. Higher score indicates disabilities	changes of Functional Outcome value from baseline to week 6