Amnion-Based Injections in the Shoulder

NCT ID: NCT03770546

Last Updated: 2021-11-26

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

WITHDRAWN

Clinical Phase

NA

Study Classification

INTERVENTIONAL

Study Start Date

2021-10-30

Study Completion Date

2023-01-31

Brief Summary

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Osteoarthritis (OA) of the shoulder is a common debilitating condition affecting up to 5% of the general population and as much as 32% of patients over 60 years of age. Clinically, OA is diagnosed by a combination of symptoms, such as slow onset of progressively worsening shoulder pain and stiffness over months to years (often with a history of minor trauma), and pain with activity. Physical exam may show tenderness and swelling, muscle atrophy, and decreased range of motion. Adhesive capsulitis (also called "Frozen Shoulder") is another common shoulder condition, affecting 2-5% of the general population. Frozen shoulder presents with a similar combination of symptoms, such as inability to sleep on the side of the affected shoulder, shoulder pain, and pain at extremes of active and passive range of motion.

Despite the ubiquitous nature of these conditions, various non-operative treatment modalities have been employed in their managements without a clearly superior alternative. The usual initial treatment strategy for both of these conditions is the same: a trial of conservative management. Conservative management includes physical therapy, supervised neglect, over-the-counter pain medications (including NSAIDs, like Advil), oral and intra-articular corticosteroid use (steroids), hydrodilatation (capsular distension to rupture), intra-articular hyaluronic acid injections. Despite several years of employing different modes of treatment, there is no evidence that places one treatment modality over the others, and patients will often need surgery.

Amniotic fluid's apparent ability to improve blood flow, re-organize collagen, and protect cartilage makes it theoretically ideal for disorders like osteoarthritis and frozen shoulder. In recent studies, it has shown efficacy in promoting ligament healing in the knee and promoting tendon and degenerative joint pain reduction and functional improvement. It has been useful as a material for cartilage repair when used as a scaffold. Intra-articular amnion membrane injection may have favorable outcomes in patients with osteoarthritis of the shoulder or frozen shoulder. To test this hypothesis, intra-articular amnion will be injected into the shoulders of 20 patients with moderate to severe osteoarthritis and 20 patients with frozen shoulder. The hypothesis is that improvement in short-term outcomes (pain, function, and range of motion) will be identified following amnion injection in these patients. The goal of this study is to lead to larger randomized controlled trials evaluating amnion against current forms of treatment for osteoarthritis.

Detailed Description

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Amnion injections are commonly performed by community orthopaedic surgeons for many conditions, including osteoarthritis, rotator cuff tears, tendinitis, and others. Human placental tissue has been reported to contain biochemical and immunologic properties that play key roles in regulation of the inflammation-healing cycle. Amnion-chorion membrane has been shown to contain high concentrations of collagens, transforming growth factor beta suppressors, and inhibitors of matrix metalloproteinases that provide strong scaffolding, suppress scar formation, and regulate tissue remodeling, respectively. The amnion injection is a morselized, flowable tissue allograft derived from human amniotic tissues. The amniotic tissue comes from placenta, donated by pre-screened healthy women undergoing scheduled C-sections. It is processed into a form that can be injected.

Similarly, in a recent study injection of micronized dehydrated human amnion-chorion membrane slowed the development of cartilaginous lesions and led to a decreased number of erosions in a rat model of osteoarthritis. There is also an emerging body of literature investigating its use in osteoarthritis of the knee, with promising early results. In one study human amniotic suspension allograft was injected into patients with symptomatic knee osteoarthritis. No significant reactions were noted and the feasibility of injection for treatment of the osteoarthritis in the knee was demonstrated. Another study found that human amniotic fluid had a positive effect on tibia fracture healing through a rat model. In an osteoarthritis model, injection demonstrated attenuation of cartilage destruction and significant increases in cartilage thickness and volume. Finally, patients with plantar fasciitis noted significant improvement in symptoms, and American Orthopaedic Foot and Ankle Society Hindfoot scores (pain, function, alignment) compared to controls. These studies suggest the safety and efficacy of amnion-based injections in treating specific orthopaedic pathologies.

Osteoarthritis and adhesive capsulitis are two common pathologies of the shoulder. There is a variety of options for conservative management including physical therapy, pain medications, and injections, but no evidence that places one modality over another. The purpose of this study is the evaluate the effectiveness of amniotic fluid injection in treating these pathologies. In this study intra-articular amnion will be injected into the shoulders of patients with moderate to severe osteoarthritis and patients with frozen shoulder and assessing pain, function and range of motion over time.

Conditions

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Osteoarthritis of the Shoulder Adhesive Capsulitis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Osteoarthritis - Amnion Injection

BioDRestore Elemental Tissue Matrix is a morselized, flowable tissue allograft derived from human amniotic tissues.

Group Type EXPERIMENTAL

Amnion Injection

Intervention Type BIOLOGICAL

Per the manufacturer, this is considered an injection of tissue/organic matter.

Osteoarthritis - Betamethasone Injection

Betamethasone Sodium Phosphate and Betamethasone Acetate injection (To clarify, this is one formulation/injected solution, not separate solutions/interventions)

Group Type ACTIVE_COMPARATOR

Betamethasone injection

Intervention Type DRUG

Routine steroid injection for these pathologies. Betamethasone Sodium Phosphate and Betamethasone Acetate injection.

Adhesive Capsulitis - Amnion Injection

BioDRestore Elemental Tissue Matrix is a morselized, flowable tissue allograft derived from human amniotic tissues.

Group Type EXPERIMENTAL

Amnion Injection

Intervention Type BIOLOGICAL

Per the manufacturer, this is considered an injection of tissue/organic matter.

Adhesive Capsulitis - Betamethasone Injection

Betamethasone Sodium Phosphate and Betamethasone Acetate injection (To clarify, this is one formulation/injected solution, not separate solutions/interventions)

Group Type ACTIVE_COMPARATOR

Betamethasone injection

Intervention Type DRUG

Routine steroid injection for these pathologies. Betamethasone Sodium Phosphate and Betamethasone Acetate injection.

Interventions

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Amnion Injection

Per the manufacturer, this is considered an injection of tissue/organic matter.

Intervention Type BIOLOGICAL

Betamethasone injection

Routine steroid injection for these pathologies. Betamethasone Sodium Phosphate and Betamethasone Acetate injection.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Age 18 years or greater
* Clinical diagnosis of adhesive capsulitis, clinically in the frozen phase at the time of enrollment OR Clinical diagnosis of osteoarthritis of the shoulder.
* Symptoms for 2-6 months
* Failure of conservative management.
* \> 25% reduction in active range of motion in \>= 2/3 planes of motion in the affected shoulder.
* No alternative medical explanation for symptoms

Exclusion Criteria

* Alternative explanation for symptoms including neurological disorders, or like conditions
* Pregnancy or desire to become pregnant
* Discretion of the enrolling clinician

Exclusion in Amnion Injection Group:

• Intra-articular steroid injection within 6 months of enrollment or surgical intervention in the within 12 months of enrollment in affected shoulder
Minimum Eligible Age

18 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Alabama at Birmingham

OTHER

Sponsor Role lead

Responsible Party

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Eugene Willis Brabston

Associate Professor, Orthopaedic Surgery

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Countries

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United States

References

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Bal A, Eksioglu E, Gulec B, Aydog E, Gurcay E, Cakci A. Effectiveness of corticosteroid injection in adhesive capsulitis. Clin Rehabil. 2008 Jun;22(6):503-12. doi: 10.1177/0269215508086179.

Reference Type BACKGROUND
PMID: 18511530 (View on PubMed)

Carette S, Moffet H, Tardif J, Bessette L, Morin F, Fremont P, Bykerk V, Thorne C, Bell M, Bensen W, Blanchette C. Intraarticular corticosteroids, supervised physiotherapy, or a combination of the two in the treatment of adhesive capsulitis of the shoulder: a placebo-controlled trial. Arthritis Rheum. 2003 Mar;48(3):829-38. doi: 10.1002/art.10954.

Reference Type BACKGROUND
PMID: 12632439 (View on PubMed)

Lorbach O, Anagnostakos K, Scherf C, Seil R, Kohn D, Pape D. Nonoperative management of adhesive capsulitis of the shoulder: oral cortisone application versus intra-articular cortisone injections. J Shoulder Elbow Surg. 2010 Mar;19(2):172-9. doi: 10.1016/j.jse.2009.06.013. Epub 2009 Oct 1.

Reference Type BACKGROUND
PMID: 19800262 (View on PubMed)

Willett NJ, Thote T, Lin AS, Moran S, Raji Y, Sridaran S, Stevens HY, Guldberg RE. Intra-articular injection of micronized dehydrated human amnion/chorion membrane attenuates osteoarthritis development. Arthritis Res Ther. 2014 Feb 6;16(1):R47. doi: 10.1186/ar4476.

Reference Type BACKGROUND
PMID: 24499554 (View on PubMed)

Vines JB, Aliprantis AO, Gomoll AH, Farr J. Cryopreserved Amniotic Suspension for the Treatment of Knee Osteoarthritis. J Knee Surg. 2016 Aug;29(6):443-50. doi: 10.1055/s-0035-1569481. Epub 2015 Dec 18.

Reference Type BACKGROUND
PMID: 26683979 (View on PubMed)

Kerimoglu S, Livaoglu M, Sonmez B, Yulug E, Aynaci O, Topbas M, Yarar S. Effects of human amniotic fluid on fracture healing in rat tibia. J Surg Res. 2009 Apr;152(2):281-7. doi: 10.1016/j.jss.2008.02.028. Epub 2008 Mar 18.

Reference Type BACKGROUND
PMID: 18499130 (View on PubMed)

Raines AL, Shih MS, Chua L, Su CW, Tseng SC, O'Connell J. Efficacy of Particulate Amniotic Membrane and Umbilical Cord Tissues in Attenuating Cartilage Destruction in an Osteoarthritis Model. Tissue Eng Part A. 2017 Jan;23(1-2):12-19. doi: 10.1089/ten.TEA.2016.0088. Epub 2016 Nov 18.

Reference Type BACKGROUND
PMID: 27707109 (View on PubMed)

Zelen CM, Poka A, Andrews J. Prospective, randomized, blinded, comparative study of injectable micronized dehydrated amniotic/chorionic membrane allograft for plantar fasciitis--a feasibility study. Foot Ankle Int. 2013 Oct;34(10):1332-9. doi: 10.1177/1071100713502179. Epub 2013 Aug 14.

Reference Type BACKGROUND
PMID: 23945520 (View on PubMed)

Other Identifiers

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IRB-300002242

Identifier Type: -

Identifier Source: org_study_id