UMIN-CTR Clinical Trial

Public title

Safety of autologous fat grafting for velopharyngeal insufficiency: non-randomized, single institution, non-blind, single arm study

Acronym

Safety study of autologous fat grafting for velopharyngeal insufficiency

Scientific Title

Safety of autologous fat grafting for velopharyngeal insufficiency: non-randomized, single institution, non-blind, single arm study

Scientific Title:Acronym

Safety study of autologous fat grafting for velopharyngeal insufficiency

Region

Japan

Condition

velopharyngeal insufficiency

Classification by specialty

Plastic surgery

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

To evaluate the safety of autologous fat grafting for patients with mild to moderate velopharyngeal insufficiency after primary cleft palate repair.

Basic objectives2

Safety

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Pragmatic

Developmental phase

Phase I

Primary outcomes

<Safety>
Airway complications in acute phase: re-intubation 24 hours within extubation, or oxygen requirement 24 hours after extubation.

Key secondary outcomes

<Safety>
1. Airway complications in late phase: DI(3)=>15 or DT90=>1 in overnight pulse oximetry at 1 and 6 months after operation.
2. Other adverse events related to surgery in acute phase: adverse events such as surgical site infection or bleeding that necessitate additional treatment 1 month within the operation.
3. Other adverse events related to surgery in late phase: adverse events such as sensory disturbance or deformation complained by patients and confirmed in medical examination at 6 months after the operation.
4. Other adverse events

<Efficacy>
1. Velopharyngeal function and its subscales (nasal emission, hyper nasality, and distortion of consonants due to nasal emission) evaluated by speech therapist in the interview at 6 months after the operation.
2. Velopharyngeal function and its subscales (nasal emission, hyper nasality, and distortion of consonants due to nasal emission) evaluated by speech therapist in the audio-visual recording at 6 months after the operation (nasal emission is based on the evaluation in the interview).
3. Speech intelligibility evaluated by speech therapist in the interview at 6 months after the operation.
4. Speech intelligibility evaluated by speech therapist in the audio-visual recording at 6 months after the operation
5. Distance of antero-posterior velopharyngeal gap evaluated in cephalogram at phonation at 1 month and 6 months after the operation.
6. Form and motility of velopharyngeal space evaluated in fiberscopy at 6 months after the operation
7. Health-related quality of life at 6 months after the operation (2 speech-related domains of CLEFT-Q Japanese version)

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

NO

Dynamic allocation

NO

Institution consideration

Blocking

Concealment

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Maneuver

Interventions/Control_1

Autologous fat grafting for velopharyngeal insufficiency:

<Pre-operative phase> Patients are admitted in the hospital one day before or on the day of the operation, after consultation with the anesthesiologists.

<Operation> Operation is performed under general anesthesia with oral intubation.
[fat harvesting] Fat is harvested from abdomen, thigh or buttocks with cannulas with tumescent method (tissues are injected with 0.15% lidocaine with 1:300000 epinephrine).
[fat extraction] Fat tissue is extracted with Coleman method (centrifugation for 3 minutes at 3000 rotations per minute).
[fat injection] Fat is injected to sub-mucosal layer of velopharyngeal walls with cannulas. Blunt-tipped cannulas are used to avoid injection into vessels. Fat is grafted evenly to promote take. Location and amount of grafting is determined based on the pre-operative fiberscopy and cephalogram. Electric stimulation of velar muscles is considered to determine the locations of grafting.

<post-operative phase> Patients are extubated in the operating room and transferred to intensive care unit (ICU) for observation of airway. Oxygen is supplied to the patients based on the protocols of the ICU. Soft diet is permitted orally after patients are awake. Patients are discharged from ICU when safety of airway is confirmed.
Patients are monitored until at least 24 hours after the operation. When patients require no oxygen and can take oral diet, they are discharged from hospital.
The following instructions are given to the patients to follow for 1 week after the operation: exercise and long-time bath are not allowed to avoid edema and bleeding; speaking loudly is not allowed to keep the surgical site stable; soft diet is continued. First hospital visit is scheduled at 1 to 4 weeks after the operation.

Details of anesthesia, operation and post-operative care are based on the protocols of the institution and determined during the actual process.

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

12

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

1: Patients with velopharyngeal insufficiency after cleft palate repair.
2: Equal to or older than 12 years old at the timing of consent.
3: IQ >70 in the IQ test performed at or older than 5 years old, or attending regular classes.
4: Velopharyngeal function is in the middle 2 grades of 4-grade evaluation in the interview by speech therapist at the institution based on the Test for Cleft Palate Speech by Japanese Association of communication Disorders, 2007.
5: Antero-posterior velopharyengeal gap is equal to or greater than 5mm in the cephalogram at phonation.
6: Velopharyngeal insufficiency is confirmed in the fiberscopy.
7: DT90<0.2%, DI(3)<5 in overnight pulse oximetry.
8: Informed consent is obtained by the patient with document for patients equal to or older than 20 years old. Informed assent is obtained by the patient and informed consent is obtained by his / her guardian with document for patients under 20 years old.

Key exclusion criteria

1: Associated with syndrome or multiple congenital anomalies which involve cleft palate as one of its features.
2: Patients under anti-coagulant therapy.
3: Patients with pre-existing infection at the surgical site.
4: Patients with malignant tumor.
5: Patients with comorbidities (such as hypertension, diabetes mellitus or metabolic disorders) that are not controlled or are advancing.
6: Patients at the risk of wound-healing (such as impaired blood flow).
7: Patients who are considered not suitable for general anesthesia by the anesthesiologists at the institution.
8: Patients who are considered not suitable for the study by the researcher of this study.

Target sample size

5

Name of lead principal investigator

1st name	Makoto
Middle name
Last name	Hikosaka

Organization

National Center for Child Health and Development

Division name

Department of Surgical Specialties, Division of Plastic Surgery

Zip code

157-8535

Address

2-10-1 Okura, Setagaya-ku, Tokyo, Japan

TEL

03-3416-0181

Email

hikosaka-m@ncchd.go.jp

Name of contact person

1st name	Makoto
Middle name
Last name	Hikosaka

Organization

National Center for Child Health and Development

Division name

Department of Surgical Specialties, Division of Plastic Surgery

Zip code

157-8535

Address

2-10-1 Okura, Setagaya-ku, Tokyo, Japan

TEL

03-3416-0181

Homepage URL

Email

hikosaka-m@ncchd.go.jp

Institute

National Center for Child Health and Development

Institute

Department

Personal name

Organization

National Center for Child Health and Development

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization

Japan

Co-sponsor

Name of secondary funder(s)

Organization

National Center for Child Health and Development

Address

2-10-1 Okura, Setagaya-ku, Tokyo, Japan

Tel

03-3416-0181

Email

tokunaga-k@ncchd.go.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

国立成育医療研究センター

Date of disclosure of the study information

2020

Year

03

Month

15

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

2

Results

On September 3rd, 2021, the first patient completed 6-month follow-up. No adverse events that are set as outcomes in the present study were observed.

Results date posted

2021

Year

09

Month

13

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Open public recruiting

Date of protocol fixation

2019

Year

11

Month

28

Day

Date of IRB

2019

Year

11

Month

28

Day

Anticipated trial start date

2020

Year

01

Month

01

Day

Last follow-up date

2023

Year

06

Month

30

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2020

Year

03

Month

03

Day

Last modified on

2023

Year

10

Month

11

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000044530