Clinical trial NCT05131269: Prolotherapy Intervention in Patient With Frozen Shoulder
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Frozen Shoulder
Keywords: MMP-1
TIMP-1
Prolotherapy
Functional Outcome
Frozen Shoulder
Lead sponsor: Hasanuddin University
Sponsor class: OTHER
First posted: 2021-11-23
Enrollment: 32
Sex: ALL
Minimum age (years): 35
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study involves two arms assigned randomly for receiving different treatments. One arm for Prolotherapy and Normal Saline in the comparison group.
Primary purpose: TREATMENT

Brief 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

Detailed 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

Eligibility criteria: 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

Primary outcomes:
measure: Matrix Metalloproteinase 1 in Blood
timeFrame: changes of Matrix Metalloproteinase 1 value from baseline to week 6
measure: Tissue Inhibitor Metalloproteinase 1 in Blood
timeFrame: changes of Tissue Inhibitor Metalloproteinase 1 value from baseline to week 6
Secondary outcomes:
measure: The Functional Outcome of the Shoulder
timeFrame: changes of Functional Outcome value from baseline to week 6
Other outcomes:
Locations:
city: Makassar
country: Indonesia
facility: Hasanuddin University, Faculty of Medicine
state: South Sulawesi
Study officials:
affiliation: Hasanuddin University
name: Nuralam Sarif, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hasanuddin University
name: Irawan Yusuf, PhD
role: STUDY_CHAIR
affiliation: Hasanuddin University
name: Endy Adnan, PhD
role: STUDY_CHAIR
affiliation: Hasanuddin University
name: Irfan Idris, PhD
role: STUDY_CHAIR
References:
citation: 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.
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.
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.
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.
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.