Clinical trial NCT04281901: Efficacy of Platelet- and Extracellular Vesicle-rich Plasma in Chronic Postsurgical Temporal Bone Inflammations
Official title: Efficacy of Platelet- and Extracellular Vesicle-rich Plasma for the Treatment of Chronically Inflamed Post-surgical Temporal Bone Cavities: a Randomised Controlled Clinical Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Otitis Media Chronic
Temporal Bone
Keywords: Otitis Media
Mastoidectomy
Wound Healing
Platelet-Rich Plasma
Extracellular Vesicles
Cholesteatoma
Regenerative Medicine
Lead sponsor: University Medical Centre Ljubljana
Sponsor class: OTHER
Collaborators: name: University of Ljubljana
name: University of Ljubljana, Faculty of Medicine
First posted: 2020-02-24
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants treated with PVRP will receive PVRP-soaked ear wicks at the day of recruitment, additionally 1 month later and then followed-up twice in 1-month intervals. Participants not treated with PVRP will be treated with standard conservative nonsurgical measures with the same follow-up time.
Primary purpose: TREATMENT

Brief summary: This clinical study evaluates the efficacy of the autologous blood-derived product called platelet- and extracellular vesicle-rich plasma (PVRP) for the treatment of chronically inflamed post-surgical temporal bone cavities. Half of the participants will be treated with platelet- and extracellular vesicle-rich plasma and another half with standard nonsurgical measures.

Detailed description: The hypothesis of this study is that platelet- and extracellular vesicle-rich plasma (PVRP) may be efficient in the treatment of chronically inflamed post-surgical temporal bone cavities.

Platelet-rich plasma (PRP) is a well-known autologous blood-derived product with favourable immune, haemostatic and regenerative effects. It has been used in various medical fields including otorhinolaryngology.

In fact, PRP contains important concentrations of extracellular vesicles (EV) which are the main contributors to PRP effects. For that reason, PRP can be identified as platelet- and extracellular vesicle-rich plasma (PVRP). In this study, PVRP will be prepared by a unique non-commercial 2-step centrifugation protocol developed by this study researchers.

A radical cavity is a large post-surgical temporal bone cavity due to removal of the posterior external ear canal wall in open-technique cholesteatoma surgery. This technique is performed in approximately 40 per cent of cholesteatoma surgery.

Radical cavities become inflamed in 3-20 per cent, which leads to the formation of granulation tissue and multiple suppurative periods. The large spectrum of surgical and nonsurgical treatment options have been applied to reduce patient discomfort. This significantly worsens the patients' quality of life and puts a significant burden on health care.

Due to the knowledge of local immune response mechanisms in moist radical cavities and exhausted treatment options, new conservative treatment options have been researched. PVRP could present a promising treatment option for chronically inflamed radical cavities based on published preclinical and clinical studies.

PVRP will be administered to chronically inflamed radical cavities via PVRP-soaked ear wicks.

Eligibility criteria: Inclusion Criteria:

* chronic otitis media, defined as a presence of at least 1 of the following: visible ear discharge, indirect signs of ear discharge (e.g. on a pillow, clothes), ear itching, the sensation of ear fullness, clinical signs of acute exacerbation of chronic otitis media during an otomicroscopic examination.
* non-cholesteatomatous chronic otitis media despite prior standard conservative treatment
* non-cholesteatomatous chronic otitis media despite prior surgical treatment

Exclusion Criteria:

* the presence or suspicion of cholesteatoma
* infection of venepuncture site
* pregnancy
* breastfeeding
* long-term treatment with antimicrobial drugs
* long-term treatment with immunosuppressant drugs
* the presence of systemic infectious disease
* the presence of an autoimmune disease
* the presence of cancer
* receiving other types of experimental treatment for chronic otitis media

Primary outcomes:
measure: Change in Inflammation Surface Area.
timeFrame: Baseline, 1 month, 2 months and 3 months after baseline
measure: Change in Chronic Otitis Media Questionnaire 12 Score
timeFrame: Baseline, 1 month, 2 months and 3 months
Secondary outcomes:
measure: Bacterial Presence
timeFrame: Baseline, 2 months
Other outcomes:
Locations:
city: Ljubljana
country: Slovenia
facility: University Medical Centre Ljubljana
Study officials:
affiliation: Department of Otorhinolaryngology and Cervicofacial Surgery, UMC Ljubljana
name: Saba Battelino, MD, PhD
role: STUDY_CHAIR
References:
citation: Vozel D, Ursic B, Krek JL, Stukelj R, Kralj-Iglic V. Applicability of extracellular vesicles in clinical studies. Eur J Clin Invest. 2017 Apr;47(4):305-313. doi: 10.1111/eci.12733. Epub 2017 Feb 28.
citation: Uršič B, Vozel D, Šuštar V, Kocjančič B, Dolinar D, Kralj-Iglič V. Extracellular Vesicles from Platelet-Rich Plasma as Conveyors of Regeneration Potential in Orthopedics. J Hematol Thromboembolic Dis 2(5), 2014.
citation: Vozel D, Bozic D, Jeran M, Jan Z, Pajnic M, Paden L, Steiner N, Kralj-Iglic V, Battelino S. Autologous Platelet- and Extracellular Vesicle-Rich Plasma Is an Effective Treatment Modality for Chronic Postoperative Temporal Bone Cavity Inflammation: Randomized Controlled Clinical Trial. Front Bioeng Biotechnol. 2021 Jul 7;9:677541. doi: 10.3389/fbioe.2021.677541. eCollection 2021.