Prolotherapy Intervention in Patient With Frozen Shoulder

NCT ID: NCT05131269

Last Updated: 2022-12-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

32 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-12-01

Study Completion Date

2022-11-30

Brief Summary

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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

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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

Conditions

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Frozen Shoulder

Keywords

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MMP-1 TIMP-1 Prolotherapy Functional Outcome Frozen Shoulder

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

This study involves two arms assigned randomly for receiving different treatments. One arm for Prolotherapy and Normal Saline in the comparison group.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

A sealed envelope of the randomized sequence was given to the investigator and care provider, and participants were recruited consecutively according to the permutation sequence. Participants were masked from the therapy by receiving treatment individually in different rooms and occasions. On the day of the assessment, the physician and laboratory technicians were blinded from group allocation

Study Groups

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Prolotherapy

A solution of 7.5 ml of 15% dextrose with 2 ml of 40% lidocaine and 10.5 water is given to these shoulder segments as follows.

1. Supraspinatus muscle 2-4 ml
2. Infraspinatus muscle 2-4 ml
3. Teres minor muscle 2-3 ml,
4. Subscapularis muscle 2-3 ml.
5. Intraarticular glenohumeral joint 5 ml
6. Bursa sub acromial 1-2 ml,
7. Long head tendon biceps 1-2 ml
8. Acromioclavicular joint 1 ml

Group Type EXPERIMENTAL

Dextrose 15 % in Water

Intervention Type DRUG

A 15% dextrose solution is given to shoulder segments four times with 2 weeks interval (week 0,2,4, and 6)

Normal Saline 0.9%

A solution of 20 ml normal saline 0.9% is given to these shoulder segments as follows.

1. Supraspinatus muscle 2-4 ml
2. Infraspinatus muscle 2-4 ml
3. Teres minor muscle 2-3 ml,
4. Subscapularis muscle 2-3 ml.
5. Intraarticular glenohumeral joint 5 ml
6. Bursa sub acromial 1-2 ml,
7. Long head tendon biceps 1-2 ml
8. Acromioclavicular joint 1 ml

Group Type PLACEBO_COMPARATOR

Normal Saline 20 mL Injection

Intervention Type DRUG

A Normal Saline 0.9% is given to shoulder segments four times with 2 weeks interval (week 0,2,4, and 6)

Interventions

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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)

Intervention Type DRUG

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)

Intervention Type DRUG

Other Intervention Names

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Prolotherapy Comparator

Eligibility Criteria

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Inclusion Criteria

1. Age 35-70
2. Diagnosed with frozen shoulder
3. At least showing symptoms more than 3 months

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
Minimum Eligible Age

35 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bumi Herman

OTHER

Sponsor Role lead

Responsible Party

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Bumi Herman

Assistant Lecturer

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Nuralam Sarif, MD

Role: PRINCIPAL_INVESTIGATOR

Hasanuddin University

Irawan Yusuf, PhD

Role: STUDY_CHAIR

Hasanuddin University

Endy Adnan, PhD

Role: STUDY_CHAIR

Hasanuddin University

Irfan Idris, PhD

Role: STUDY_CHAIR

Hasanuddin University

Locations

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Hasanuddin University, Faculty of Medicine

Makassar, South Sulawesi, Indonesia

Site Status

Countries

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Indonesia

References

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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.

Reference Type BACKGROUND
PMID: 32990454 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29992159 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21703585 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23604641 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28027657 (View on PubMed)

Other Identifiers

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0411211741

Identifier Type: -

Identifier Source: org_study_id