Multicenter Trial of autologous nasal mucosal epithelial cell sheets for chronic middle ear inflammatory disease (middle ear cholesteatoma)

JRCT ID: jRCT2033210438

Registered date:22/11/2021

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Chronic middle ear inflammatory disease (middle ear cholesteatoma)
• Date of first enrollment: 13/12/2021
• Target sample size: 12
• Study type: Interventional
• Intervention(s): After conventional tympanoplasty under general anesthesia is performed, hemostasis is confirmed sufficiently before the skin is closed, a surgical instrument with a nasal mucosal epithelial cell sheet is transferred to the transplantation wound, and the nasal mucosal epithelial cell sheet is transferred from the surgical instrument to the middle ear mucosal defect, i.e., the exposed bone surface, and transplanted without sutures. Alternatively, a nasal mucosal epithelial cell sheet is placed on a sterile silicone plate and transferred to the transplantation wound, and then the sheet is transferred from the silicone plate for transplantation. Thereafter, the skin wo und is closed and the operation is completed in the same manner as the usual tympanoplasty.

Outcome(s)

Primary Outcome

Efficacy endpoints
1) With or without aeration in the mastoid cavity 48 weeks after transplantation.

Secondary Outcome

Efficacy endpoints
1) Evaluation based on postoperative results using the Japan Otological Society criteria (postoperative air-bone gap, hearing improvement, and postoperative hearing level).
2) Presence or absence of tympanic membrane adhesions
3) Presence or absence of a recurrent cholesteatoma
4) Evaluation of aeration in the mastoid cavity over time (with or without air content)
5) Evaluation of the presence of aeration in the tympanic cavity over time (with and without air content)

Safety endpoints
1) Important safety endpoints
Number of subjects with exacerbation of inflammation in the middle ear cavity for which a causal relationship to the investigational product transplantation could not be ruled out and the incidence (%)
2) Number of cases of adverse events and failure and incidence (%).
3) Number of cases of significant failure and incidence (%).

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: < 75age old
• Gender: Both

Include criteria

1) Patients diagnosed with pars flaccida and pars tensa cholesteatoma and classified as Stage II or Stage III AO (adhesive otitis) according to the staging of middle ear cholesteatoma (2015).
2) Patients undergoing tympanoplasty with mastoidectomy. Patients who have undergone canal wall down without reconstruction, or mastoid obliteration are excluded.
3) Patients aged >=18 and <75 at the time of consent acquisition.
4) Patients who have received sufficient explanation in participating in this study, and then, with sufficient understanding, have received written consent from the patient's own free will.
5) Outpatients who can attend the clinic according to the study schedule.

Exclude criteria

1) Congenital cholesteatoma; secondary cholesteatoma; Combination of pars flaccida and pars tensa cholesteatoma; unclassifiable type cholesteatoma.
2) Patients with a preoperative air density area in the mastoid cavity =>50 mm^2 in the temporal bone CT horizontal section.
3) Patients with obvious scarring of the nasal mucosa at the site making harvesting impossible.
4) Patients with contraindications to antibacterial agents or anesthetics used in this study.
5) Patients with hypersensitivity to penicillin, kanamycin, streptomycin, or amphotericin B antibiotics. Patients with a history of hypersensitivity to penicillin or aminoglycoside antibiotics.
6) Patients with a history of hypersensitivity to animals (bovine, mouse or pig).
7) Patients with less than 5 years history of malignancy or suspected of having malignancy.
8) Diabetic patients with poor glycemic control.
9) Patients in whom complications, etc. were observed in the transplanted ear of the investigational product or the entire body, and the investigator or subinvestigator judged it difficult to evaluate.
10) Pregnant women, breastfeeding women or patients who may be pregnant or patients who wish to become pregnant during the study period.
11) Patients who have participated in other clinical trials within 3 months prior to the transplantation of the investigational product, patients who have participated in other clinical trials, and patients who are scheduled to participate in other clinical trials while participating in this clinical trial.
12) Patients judged inappropriate for the study by the investigator or sub-investigator.

Related Information

• Primary Sponsor: Yamamoto Kazuhisa
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development