Ignite Creation Date:
2024-10-26 @ 3:42 PM
Last Modification Date:
2024-10-26 @ 3:42 PM
Study NCT ID:
NCT06639009
Status:
RECRUITING
Last Update Posted:
None
First Post:
2024-10-10
Brief Title:
Effect of Laser Photobiomodulation in Improving Mouth Opening in Oral Submucous Fibrosis
Sponsor:
None
Organization:
None
Study Overview
Official Title:
To Determine and Compare the Adjunctive Effect of Photobiomodulation With 940nm Diode Laser on Maximal Interincisal Mouth Opening Versus Conventional Non-invasive Management in Moderate Oral Submucous Fibrosis A Patient and Outcome Assessor Blinded Multiple- Arm Randomized Placebo Controlled Clinical Trial
Status:
RECRUITING
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
OSMFPBMT
Brief Summary:
This a patient and outcome assessor blinded multiple arm randomized placebo controlled clinical trial
The goal of the study is to study the adjunctive effect of 940nm laser photobiomodulation therapy PBMT in precancerous condition like moderate Oral submucous Fibrosis in increasing the mouth opening It will also assess the the effect of PBMT on oral burning sensation cheek flexibility electromyography of bilateral masseter muscle inflammatory and fibrogenic cytokines and oral health quality of life at baseline and after 1 and 3 months of PBMT
Adult subjects fulfilling the selection criteria will be prospectively recruited after ethical clearance and informed written consent They will be randomized into 3 groups in 11 1 distribution
The three groups are as follows
Group A Photobiomodulation therapy given intraorally on bilateral buccal mucosa and extraorally sham with conventional non-invasive management
Group B Photobiomodulation therapy given intraorally bilateral buccal mucosa and extraorally bilateral masseter muscle with conventional non-invasive management
Group C Sham Use of laser handpiece with only red guide light and without using the foot pedal which activates the laserPhotobiomodulation therapyPlacebo Intraoral and Extraoral with conventional non-invasive management
The conventional non invasive management in Oral submucous fibrosis which all the groups will receive are as follows
Brief behavioral Tobacco areca nut and alcohol habit cessation counseling as per WHO 5As and 5Rs technique at baseline and each follow up
Oral prophylaxis Removal of oral irritational factors like sharp teeth appliances or prosthesis impacted buccoverted third molars parafunctional habits Oral hygiene maintenance instructions Oral physiotherapyMouth opening and cheek ballooning exercises Control of systemic conditions Anemia Diabetes hypertension thyroid disorders by specialist referral Removal of all predisposing factors for oral candida infection Advocacy for safe sexual practices Nutrition and diet counseling seasonal and regional food rich in nutrients vitamins antioxidants avoidance of spicy sour hot foods and drinks Regular surveillance for malignant transformation All the outcome parameters will be assessed at baseline and 1 and 3 months after PBMT
The goal of the study is to study the adjunctive effect of 940nm laser photobiomodulation therapy PBMT in precancerous condition like moderate Oral submucous Fibrosis in increasing the mouth opening It will also assess the the effect of PBMT on oral burning sensation cheek flexibility electromyography of bilateral masseter muscle inflammatory and fibrogenic cytokines and oral health quality of life at baseline and after 1 and 3 months of PBMT
Adult subjects fulfilling the selection criteria will be prospectively recruited after ethical clearance and informed written consent They will be randomized into 3 groups in 11 1 distribution
The three groups are as follows
Group A Photobiomodulation therapy given intraorally on bilateral buccal mucosa and extraorally sham with conventional non-invasive management
Group B Photobiomodulation therapy given intraorally bilateral buccal mucosa and extraorally bilateral masseter muscle with conventional non-invasive management
Group C Sham Use of laser handpiece with only red guide light and without using the foot pedal which activates the laserPhotobiomodulation therapyPlacebo Intraoral and Extraoral with conventional non-invasive management
The conventional non invasive management in Oral submucous fibrosis which all the groups will receive are as follows
Brief behavioral Tobacco areca nut and alcohol habit cessation counseling as per WHO 5As and 5Rs technique at baseline and each follow up
Oral prophylaxis Removal of oral irritational factors like sharp teeth appliances or prosthesis impacted buccoverted third molars parafunctional habits Oral hygiene maintenance instructions Oral physiotherapyMouth opening and cheek ballooning exercises Control of systemic conditions Anemia Diabetes hypertension thyroid disorders by specialist referral Removal of all predisposing factors for oral candida infection Advocacy for safe sexual practices Nutrition and diet counseling seasonal and regional food rich in nutrients vitamins antioxidants avoidance of spicy sour hot foods and drinks Regular surveillance for malignant transformation All the outcome parameters will be assessed at baseline and 1 and 3 months after PBMT
Detailed Description:
Study design
A patient and outcome assessor blinded multiple- arm randomized placebo controlled clinical trial Setting All India Institute of Medical sciences New Delhi
Selection of patients
Consecutive patients diagnosed with Oral Submucous Fibrosis based on WHO clinical criteria Warnakulsurya et al 2007 2021 and classified as Moderate Oral Submucous Fibrosis based on functional staging of More et al 2011 Functional staging M2 and M3 maximal interincisal distance 15-35 mm will be prospectively recruited after ethical clearance and informed written consent
Clinicopathologic characteristics
The clinical demographics Tobacco and Areca nut habit history Type quantity frequency duration association with other habits like smoking smokeless tobacco with without slaked lime alcohol and addictive drugs will be recorded The clinical characteristics and staginggrading of OSMF would be recorded as per prepared proforma and protocol The clinical grading of moderate OSMF will be done according to WHO clinical criteria and More et al 2011 classification Biopsy of any suspicious oral lesions if found will be done to rule out malignancy and referred to the cancer center for further management and excluded from study Enrolment of subjects fulfilling the inclusion and none of the exclusion criteria will be done after information and written informed consent before any further investigation Routine blood investigations to rule out common systemic conditions CBC Blood glucose LFT KFT Participants will be randomized into three arms 111 Group A Photobiomodulation therapy parameters defined below given intraorally on bilateral buccal mucosa and extraorally sham with conventional non-invasive management
Group B Photobiomodulation therapy parameters defined below given intraorally bilateral buccal mucosa and extraorally bilateral masseter muscle with conventional non-invasive management
Group C Sham Use of laser handpiece with only red guide light and without using the foot pedal which activates the laserPhotobiomodulation therapyPlacebo Intraoral and Extraoral with conventional non-invasive management
Randomization
Block randomization with varying block size will be done using computer generated random numbers using the Nquery software
Allocation concealment
Participants will be randomized using sequentially numbered opaque sealed envelopes SNOSE 315 white envelopes will be prepared with aluminum foil sheet and carbon sheet in each Assigned treatment protocol will be mentioned clearly on a paper and put in each envelope For each treatment protocol 105 envelopes will be prepared and sealed Each envelope will have an identifier of trial on its front Envelopes will be opened sequentially by an operator blinded to the study protocol after which patients will be allotted a study arm as per the treatment mentioned in the envelope Before opening the envelope we will write the patients study identifier number date and operators signature in front of the envelope which will be transferred on white paper through carbon paper Used envelopes will be stored separately until the completion of trial
Blinding
The subjects will be blinded to the group assignment as they will receive PBM Active or Sham as per group assignment both intraorally and extraorally The outcome assessor will be blinded to the group assignment of the subjects as they will be identified by unique randomization code only
Conventional non-invasive management Usual care
All subjects in the three groups will receive the same standard conventional non- invasive management advised for moderate OSMF as per current scientific evidence
Brief behavioral Tobacco areca nut and alcohol habit cessation counseling as per WHO 5As and 5Rs technique at baseline and each follow up
Oral prophylaxis Removal of oral irritational factors like sharp teeth appliances or prosthesis impacted buccoverted third molars parafunctional habits Oral hygiene maintenance instructions Oral physiotherapyMouth opening and cheek ballooning exercises Control of systemic conditions Anemia Diabetes hypertension thyroid disorders by specialist referral Removal of all predisposing factors for oral candida infection Advocacy for safe sexual practices Nutrition and diet counseling seasonal and regional food rich in nutrients vitamins antioxidants avoidance of spicy sour hot foods and drinks Regular surveillance for malignant transformation
Photobiomodulation Therapy PBM therapy
PBM will be given with 940nm long infrared wavelength diode laser with following specifications Biolase Epic X Diode LASER USFDA and CE approved LASER Classification- IV Medium- InGaAsP Semi-Conductor Diode Wavelength- 94010nm Maximum Output Power 10W Pulse repetition rate upto 20kHz Pulse duration Rate 001ms- 20ms Power modes- Continuous Pulsed Protocol for PhotoBioModulation PBM therapy Protocol for PBM therapy has been made as per guidelines of the consensus statement Zelcha et al 2016 regarding the applications protocols safety dosimetric considerations of PBM in management of side effects of chemoradiation therapy in Head and neck cancers like mucositis and fibrosis
Protective laser wavelength specific eyewear will be used for patient operator The device will be used according to the manufacturers instructions and calibration before each therapy in the trial The surgical handpiece diameter 06cm will be used without the fibre optic tips in defocused mode and head sanitized before therapy
Peak Power 03Watts Power density 1 Wattcm2 Fluence 4Jcm2 per cycle Spot size 028cm2 Distance 2mm from surface Mode Continuous Non- contact mode circular motion overlapping in clockwise concentric manner with laser handpiece perpendicular to surface Duration of cycle 20 seconds with interval of 30 seconds alternating with other side Cycles per sitting Three for each side Four Sittings Day 03 7 and 15 Intraoral Bilateral buccal mucosa will be divided arbitrarily into three zones superior middle and inferior for equal distribution of laser energy during each cycle Extraoral Bilateral masseter muscle will be divided into three zones superior middle and inferior for equal distribution of laser energy during each cycle Therapeutic monitoring Site of application of LASER will be evaluated continuously for any discomfort signs of inflammation like redness of skin mucosa during therapy and during follow up The following options will be considered during therapy Move the Handpiece relative to the affected anatomy Defocus the energy by moving the Handpiece further away from the skin Decrease the power settingconsidering the Fitzpatrick Skin type scale Stop Defer the treatment Patient will be interviewed to know any adverse effects they might be feeling after initiation of treatment with Laser
Training of operators
All the operators giving intraoral and extraoral PBM therapy will be trained in the protocol as per study before subject recruitment
Withdrawal criteria If any patient withdraws consent after treatment is initiated or develops any of the conditions mentioned in exclusion criteria the patient will be withdrawn from the study
Protocol Deviation WhenIf subjects develop changes suspicious of malignancy erosion ulceration induration exophytic growth during follow up after Usual carePBM they will undergo incisional biopsy to rule out malignant changes and managed as per institutional protocol for oral malignant lesions by referral to cancer center at IRCH
Statistical Analysis Data will be entered in an electronic data form and managed using Research Electronic Data Capture REDcap software Comparison of baseline continuous variables will be compared between the two groups A and C B and C using Unpaired T-test and categorical variables will be compared using Chi Squared Test or Fishers Exact Test The primary outcome measure- Interincisal Distance at maximum mouth opening will be compared between the two groups using Unpaired T-test and analyzed using Intention to Treat and Per Protocol Analysis Secondary continuous outcome variables will be compared between the two groups using Unpaired T-test or Wilcoxon Rank Test as appropriate Secondary categorical outcome variables will be compared between the two groups for two proportionsZ-test Comparison between primary and secondary outcome variables between groups A and B will also be done using the same scheme although the sample size is not estimated for the same Results will be presented as Difference in MeansProportions with 95 confidence interval and p005 will be considered statistically significant
A patient and outcome assessor blinded multiple- arm randomized placebo controlled clinical trial Setting All India Institute of Medical sciences New Delhi
Selection of patients
Consecutive patients diagnosed with Oral Submucous Fibrosis based on WHO clinical criteria Warnakulsurya et al 2007 2021 and classified as Moderate Oral Submucous Fibrosis based on functional staging of More et al 2011 Functional staging M2 and M3 maximal interincisal distance 15-35 mm will be prospectively recruited after ethical clearance and informed written consent
Clinicopathologic characteristics
The clinical demographics Tobacco and Areca nut habit history Type quantity frequency duration association with other habits like smoking smokeless tobacco with without slaked lime alcohol and addictive drugs will be recorded The clinical characteristics and staginggrading of OSMF would be recorded as per prepared proforma and protocol The clinical grading of moderate OSMF will be done according to WHO clinical criteria and More et al 2011 classification Biopsy of any suspicious oral lesions if found will be done to rule out malignancy and referred to the cancer center for further management and excluded from study Enrolment of subjects fulfilling the inclusion and none of the exclusion criteria will be done after information and written informed consent before any further investigation Routine blood investigations to rule out common systemic conditions CBC Blood glucose LFT KFT Participants will be randomized into three arms 111 Group A Photobiomodulation therapy parameters defined below given intraorally on bilateral buccal mucosa and extraorally sham with conventional non-invasive management
Group B Photobiomodulation therapy parameters defined below given intraorally bilateral buccal mucosa and extraorally bilateral masseter muscle with conventional non-invasive management
Group C Sham Use of laser handpiece with only red guide light and without using the foot pedal which activates the laserPhotobiomodulation therapyPlacebo Intraoral and Extraoral with conventional non-invasive management
Randomization
Block randomization with varying block size will be done using computer generated random numbers using the Nquery software
Allocation concealment
Participants will be randomized using sequentially numbered opaque sealed envelopes SNOSE 315 white envelopes will be prepared with aluminum foil sheet and carbon sheet in each Assigned treatment protocol will be mentioned clearly on a paper and put in each envelope For each treatment protocol 105 envelopes will be prepared and sealed Each envelope will have an identifier of trial on its front Envelopes will be opened sequentially by an operator blinded to the study protocol after which patients will be allotted a study arm as per the treatment mentioned in the envelope Before opening the envelope we will write the patients study identifier number date and operators signature in front of the envelope which will be transferred on white paper through carbon paper Used envelopes will be stored separately until the completion of trial
Blinding
The subjects will be blinded to the group assignment as they will receive PBM Active or Sham as per group assignment both intraorally and extraorally The outcome assessor will be blinded to the group assignment of the subjects as they will be identified by unique randomization code only
Conventional non-invasive management Usual care
All subjects in the three groups will receive the same standard conventional non- invasive management advised for moderate OSMF as per current scientific evidence
Brief behavioral Tobacco areca nut and alcohol habit cessation counseling as per WHO 5As and 5Rs technique at baseline and each follow up
Oral prophylaxis Removal of oral irritational factors like sharp teeth appliances or prosthesis impacted buccoverted third molars parafunctional habits Oral hygiene maintenance instructions Oral physiotherapyMouth opening and cheek ballooning exercises Control of systemic conditions Anemia Diabetes hypertension thyroid disorders by specialist referral Removal of all predisposing factors for oral candida infection Advocacy for safe sexual practices Nutrition and diet counseling seasonal and regional food rich in nutrients vitamins antioxidants avoidance of spicy sour hot foods and drinks Regular surveillance for malignant transformation
Photobiomodulation Therapy PBM therapy
PBM will be given with 940nm long infrared wavelength diode laser with following specifications Biolase Epic X Diode LASER USFDA and CE approved LASER Classification- IV Medium- InGaAsP Semi-Conductor Diode Wavelength- 94010nm Maximum Output Power 10W Pulse repetition rate upto 20kHz Pulse duration Rate 001ms- 20ms Power modes- Continuous Pulsed Protocol for PhotoBioModulation PBM therapy Protocol for PBM therapy has been made as per guidelines of the consensus statement Zelcha et al 2016 regarding the applications protocols safety dosimetric considerations of PBM in management of side effects of chemoradiation therapy in Head and neck cancers like mucositis and fibrosis
Protective laser wavelength specific eyewear will be used for patient operator The device will be used according to the manufacturers instructions and calibration before each therapy in the trial The surgical handpiece diameter 06cm will be used without the fibre optic tips in defocused mode and head sanitized before therapy
Peak Power 03Watts Power density 1 Wattcm2 Fluence 4Jcm2 per cycle Spot size 028cm2 Distance 2mm from surface Mode Continuous Non- contact mode circular motion overlapping in clockwise concentric manner with laser handpiece perpendicular to surface Duration of cycle 20 seconds with interval of 30 seconds alternating with other side Cycles per sitting Three for each side Four Sittings Day 03 7 and 15 Intraoral Bilateral buccal mucosa will be divided arbitrarily into three zones superior middle and inferior for equal distribution of laser energy during each cycle Extraoral Bilateral masseter muscle will be divided into three zones superior middle and inferior for equal distribution of laser energy during each cycle Therapeutic monitoring Site of application of LASER will be evaluated continuously for any discomfort signs of inflammation like redness of skin mucosa during therapy and during follow up The following options will be considered during therapy Move the Handpiece relative to the affected anatomy Defocus the energy by moving the Handpiece further away from the skin Decrease the power settingconsidering the Fitzpatrick Skin type scale Stop Defer the treatment Patient will be interviewed to know any adverse effects they might be feeling after initiation of treatment with Laser
Training of operators
All the operators giving intraoral and extraoral PBM therapy will be trained in the protocol as per study before subject recruitment
Withdrawal criteria If any patient withdraws consent after treatment is initiated or develops any of the conditions mentioned in exclusion criteria the patient will be withdrawn from the study
Protocol Deviation WhenIf subjects develop changes suspicious of malignancy erosion ulceration induration exophytic growth during follow up after Usual carePBM they will undergo incisional biopsy to rule out malignant changes and managed as per institutional protocol for oral malignant lesions by referral to cancer center at IRCH
Statistical Analysis Data will be entered in an electronic data form and managed using Research Electronic Data Capture REDcap software Comparison of baseline continuous variables will be compared between the two groups A and C B and C using Unpaired T-test and categorical variables will be compared using Chi Squared Test or Fishers Exact Test The primary outcome measure- Interincisal Distance at maximum mouth opening will be compared between the two groups using Unpaired T-test and analyzed using Intention to Treat and Per Protocol Analysis Secondary continuous outcome variables will be compared between the two groups using Unpaired T-test or Wilcoxon Rank Test as appropriate Secondary categorical outcome variables will be compared between the two groups for two proportionsZ-test Comparison between primary and secondary outcome variables between groups A and B will also be done using the same scheme although the sample size is not estimated for the same Results will be presented as Difference in MeansProportions with 95 confidence interval and p005 will be considered statistically significant
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None