Laser Therapy to Treat the Dry Mouth of Sjogren's Syndrome

• Sponsor: Federal University of São Paulo (Other)
• Overall Status: Completed
• CT.gov ID: NCT02066896
• Collaborator: (none)
• Enrollment: 66
• Location: 1
• Arms: 2
• Duration (Months): 27
• Patients Per Site Per Month: 2.4

Study Details

Study Description

Brief Summary

This study was designed to test the efficacy and safety of low laser therapy to treat the xerostomia of patients with primary Sjogren's Syndrome.

Condition or Disease	Intervention/Treatment	Phase
KERATOCONJUNCTIVITIS SICCA; XEROSTOMIA; SICCA SYNDROME; PRIMARY SJOGREN SYNDROME	Device: Lasertherapy; Device: Sham Lasertherapy	N/A

Detailed Description

The Sjogren's Syndrome is a disease that affects around 0,5% of the population and is mainly characterized for inflammatory involvement of salivary and lacrimal glands.

The xerostomia leads to low quality of life caused by dry sensations that can disturb the taste, the speaking, the swallow and chewing functions in the affected patients. The absent saliva can cause increase of dental caries and decays.

Until now, there is no effective treatment that increases the amount of saliva and the patients have low improvements with cholinergic drugs such as pilocarpine and cevimeline. These drugs can cause unpleasant collateral effects.

Study Design

• Study Type: Interventional
• Actual Enrollment: 66 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Low Level Laser Therapy For The Treatment Of Xerostomia In Primary Sjogren's Syndrome
• Study Start Date: May 1, 2014
• Actual Primary Completion Date: Aug 1, 2016
• Actual Study Completion Date: Aug 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Sham Comparator: Sham Comparator: Sham Lasertherapy Sham lasertherapy in parotid, submandibular and sublingual glands for six weeks.	Device: Sham Lasertherapy; Laser 808 wave length infrared Ga AlAs(gallium-aluminum-arsenide).The device will be applied with the laser pen closed by aluminium foil (placebo group).
Active Comparator: Active Comparator: Lasertherapy Low level lasertherapy in parotid, submandibular and sublingual glands for six weeks.	Device: Lasertherapy; Laser 808 wave length infrared Ga AlAs(gallium-aluminum-arsenide). The laser beam applied bilaterally in non contact mode to each salivary gland area, extra orally to the parotid and submandibular glands and intramurally to the sublingual gland/ 4 Joules/cm2 each point (active group)

Outcome Measures

Primary Outcome Measures

1. The Xerostomia Inventory [6 weeks]

   The Xerostomia Inventory (XI) is an 11-item questionnaire (Thomson et al, 1999). Scores to the 11 items are summated, providing a single score (5-55) representing the subjective severity of xerostomia. In 2012, da Mata published a validated version in portuguese and we used this version. The better score is the lowest. The significant variation is defined as 6 or more. Bellow we describe all the 11 questions: I sip liquids to aid in swallowing food My mouth feels dry when eating a meal I get up at night to drink My mouth feels dry I have difficulty in eating dry foods I suck sweets or cough lollies to relieve dry mouth I have difficulties swallowing certain foods The skin of my face feels dry My eyes feel dry My lips feel dry The inside of my nose feels dry __________________________________________________________ Score: Never' (1), Hardly ever' (2), Occasionally' (3), Fairly often' (4), Very often' (5)

Secondary Outcome Measures

1. Salivary Biomarker Analysis. Beta 2 Microglobulin. [6 weeks]

   The saliva in Sögren's syndrome patients has a high level of beta 2 microglobulin reflecting progression of the disease and inflammatory process at glandular epithelium. The saliva samples were collected at the baseline and end point. Beta 2 microglobulin was determined by Elisa human kit (ABCAM ab 108885). The normal levels are 1,2 +/- 0,7 microg/ml, and for primary Sjögren's syndrome 5,3 +/- 4,6 microg/ml. This measure was done in the samples of saliva before and after the lasertherapy for all patients.

2. Salivary Flux Measurement [6 weeks]

   The salivary flux was measured at the same time, without previous meal or tooth brushing, drinking or eating, in a quiet room. Spilled saliva was collected in a graduated Falcon 15ml tube. The samples of saliva were frozen and stored at -20° C. Normal salivary stimulated flux is above 0,5 ml/min. Normal unstimulated salivary flux is above 0,2 ml/min.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with primary Sjogren Syndrome according criteria american european 2002.

• Salivary flux non stimulated < 0,1 ml/min.

Exclusion Criteria:

• hepatitis B and/or C

• radiotherapy in the glandular area (previous)

• other connective diseases

• thyroidopathy non compensated

• GVHD graft-versus-host disease

• HIV

• Sarcoidosis

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Tania S A Fidelix	Sao Paulo		Brazil	04602-000

Sponsors and Collaborators

• Federal University of São Paulo

Investigators

• Study Chair: Virginia M Trevisani, PhD, Federal University of Sao Paulo

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: TANIA SALES DE ALENCAR FIDELIX, DR., Federal University of São Paulo
• ClinicalTrials.gov Identifier: NCT02066896
• Other Study ID Numbers: LLLXS
• First Posted: Feb 20, 2014
• Last Update Posted: Aug 3, 2017
• Last Verified: Apr 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Keywords provided by TANIA SALES DE ALENCAR FIDELIX, DR., Federal University of São Paulo: Sjogrens Syndrome; Syndrome, Sjogren's; Sjogren Syndrome; Sicca Syndrome; Syndrome, Sicca
• Additional relevant MeSH terms: Sjogren's Syndrome; Xerostomia; Keratoconjunctivitis; Keratoconjunctivitis Sicca; Dry Eye Syndromes; Syndrome

Study Results

Participant Flow

Recruitment Details	The study sample consisted of 66 patients who were selected from 84 patients referred from ophthalmology and rheumatology division of university hospital. The patients met primary Sjögren's criteria (2002).
Pre-assignment Detail	The exclusion criteria were: sarcoidosis, uncontrolled thyroidopathy, HIV and HCV infections and head or neck irradiation history. A computer-generated randomization list was used to allocate patients ramdomly into two groups: active laser therapy and sham laser therapy. Concealed randomization was performed with opaque sealed envelopes.

Arm/Group Title	Sham Comparator: Sham Lasertherapy	Active Comparator: Lasertherapy
Arm/Group Description	Sham lasertherapy in parotid, submandibular and sublingual glands for six weeks. Sham Lasertherapy: Laser 808 wave length infrared Ga AlAs(gallium-aluminum-arsenide).The device will be applied with the laser pen closed by aluminium foil (placebo group).	Low level lasertherapy in parotid, submandibular and sublingual glands for six weeks. Lasertherapy: Laser 808 wave length infrared Ga AlAs(gallium-aluminum-arsenide). The laser beam applied bilaterally in non contact mode to each salivary gland area, extra orally to the parotid and submandibular glands and intramurally to the sublingual gland/ 4 Joules/cm2 each point (active group)
Period Title: Overall Study
STARTED	33	33
COMPLETED	33	33
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Sham Comparator: Sham Lasertherapy	Active Comparator: Lasertherapy	Total
Arm/Group Description	Sham lasertherapy in parotid, submandibular and sublingual glands for six weeks. Sham Lasertherapy: Laser 808 wave length infrared Ga AlAs(gallium-aluminum-arsenide).The device will be applied with the laser pen closed by aluminium foil (placebo group).	Low level lasertherapy in parotid, submandibular and sublingual glands for six weeks. Lasertherapy: Laser 808 wave length infrared Ga AlAs(gallium-aluminum-arsenide). The laser beam applied bilaterally in non contact mode to each salivary gland area, extra orally to the parotid and submandibular glands and intramurally to the sublingual gland/ 4 Joules/cm2 each point (active group)	Total of all reporting groups
Overall Participants	33	33	66
Age (years (SD)) [Median (Standard Deviation) ]
Median (Standard Deviation) [years (SD)]	58 (11.1)	54 (11.3)	57 (11.0)
Sex: Female, Male (Count of Participants)
Female	32 97%	32 97%	64 97%
Male	1 3%	1 3%	2 3%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
Brazil	33 100%	33 100%	66 100%

Outcome Measures

1. Primary Outcome

Title	The Xerostomia Inventory
Description	The Xerostomia Inventory (XI) is an 11-item questionnaire (Thomson et al, 1999). Scores to the 11 items are summated, providing a single score (5-55) representing the subjective severity of xerostomia. In 2012, da Mata published a validated version in portuguese and we used this version. The better score is the lowest. The significant variation is defined as 6 or more. Bellow we describe all the 11 questions: I sip liquids to aid in swallowing food My mouth feels dry when eating a meal I get up at night to drink My mouth feels dry I have difficulty in eating dry foods I suck sweets or cough lollies to relieve dry mouth I have difficulties swallowing certain foods The skin of my face feels dry My eyes feel dry My lips feel dry The inside of my nose feels dry __________________________________________________________ Score: Never' (1), Hardly ever' (2), Occasionally' (3), Fairly often' (4), Very often' (5)
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

Intent to treat population. Last observation carried forward imputation method.

Arm/Group Title	Sham Comparator: Sham Lasertherapy	Active Comparator: Lasertherapy
Arm/Group Description	Sham lasertherapy in parotid, submandibular and sublingual glands for six weeks. Sham Lasertherapy: Laser 808 wave length infrared Ga AlAs(gallium-aluminum-arsenide).The device will be applied with the laser pen closed by aluminium foil (placebo group).	Low level lasertherapy in parotid, submandibular and sublingual glands for six weeks. Lasertherapy: Laser 808 wave length infrared Ga AlAs(gallium-aluminum-arsenide). The laser beam applied bilaterally in non contact mode to each salivary gland area, extra orally to the parotid and submandibular glands and intramurally to the sublingual gland/ 4 Joules/cm2 each point (active group)
Measure Participants	33	33
Mean (Standard Deviation) [units on a scale]	40.2 (8.3)	39.3 (8.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sham Comparator: Sham Lasertherapy, Active Comparator: Lasertherapy
	Comments
	Type of Statistical Test	Other
	Comments	ANOVA repeated measures
Statistical Test of Hypothesis	p-Value	0.05
	Comments
	Method	ANOVA
	Comments	ANOVA repeated measures

2. Secondary Outcome

Title	Salivary Biomarker Analysis. Beta 2 Microglobulin.
Description	The saliva in Sögren's syndrome patients has a high level of beta 2 microglobulin reflecting progression of the disease and inflammatory process at glandular epithelium. The saliva samples were collected at the baseline and end point. Beta 2 microglobulin was determined by Elisa human kit (ABCAM ab 108885). The normal levels are 1,2 +/- 0,7 microg/ml, and for primary Sjögren's syndrome 5,3 +/- 4,6 microg/ml. This measure was done in the samples of saliva before and after the lasertherapy for all patients.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sham Comparator: Sham Lasertherapy	Active Comparator: Lasertherapy
Arm/Group Description	Sham lasertherapy in parotid, submandibular and sublingual glands for six weeks. Sham Lasertherapy: Laser 808 wave length infrared Ga AlAs(gallium-aluminum-arsenide).The device will be applied with the laser pen closed by aluminium foil (placebo group).	Low level lasertherapy in parotid, submandibular and sublingual glands for six weeks. Lasertherapy: Laser 808 wave length infrared Ga AlAs(gallium-aluminum-arsenide). The laser beam applied bilaterally in non contact mode to each salivary gland area, extra orally to the parotid and submandibular glands and intramurally to the sublingual gland/ 4 Joules/cm2 each point (active group)
Measure Participants	33	33
Median (Standard Deviation) [microg/ml]	1.10 (3.63)	0.84 (4.93)

3. Secondary Outcome

Title	Salivary Flux Measurement
Description	The salivary flux was measured at the same time, without previous meal or tooth brushing, drinking or eating, in a quiet room. Spilled saliva was collected in a graduated Falcon 15ml tube. The samples of saliva were frozen and stored at -20° C. Normal salivary stimulated flux is above 0,5 ml/min. Normal unstimulated salivary flux is above 0,2 ml/min.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sham Comparator: Sham Lasertherapy	Active Comparator: Lasertherapy
Arm/Group Description	Sham lasertherapy in parotid, submandibular and sublingual glands for six weeks. Sham Lasertherapy: Laser 808 wave length infrared Ga AlAs(gallium-aluminum-arsenide).The device will be applied with the laser pen closed by aluminium foil (placebo group).	Low level lasertherapy in parotid, submandibular and sublingual glands for six weeks. Lasertherapy: Laser 808 wave length infrared Ga AlAs(gallium-aluminum-arsenide). The laser beam applied bilaterally in non contact mode to each salivary gland area, extra orally to the parotid and submandibular glands and intramurally to the sublingual gland/ 4 Joules/cm2 each point (active group)
Measure Participants	33	33
Median (Standard Deviation) [ml/min]	0.100 (0.164)	0.100 (0.114)

Adverse Events

Time Frame	10 weeks
Arm/Group Title	Sham Comparator: Sham Lasertherapy		Active Comparator: Lasertherapy
Arm/Group Description	Sham lasertherapy in parotid, submandibular and sublingual glands for six weeks. Sham Lasertherapy: Laser 808 wave length infrared Ga AlAs(gallium-aluminum-arsenide).The device will be applied with the laser pen closed by aluminium foil (placebo group).		Low level lasertherapy in parotid, submandibular and sublingual glands for six weeks. Lasertherapy: Laser 808 wave length infrared Ga AlAs(gallium-aluminum-arsenide). The laser beam applied bilaterally in non contact mode to each salivary gland area, extra orally to the parotid and submandibular glands and intramurally to the sublingual gland/ 4 Joules/cm2 each point (active group)
All Cause Mortality
	Sham Comparator: Sham Lasertherapy		Active Comparator: Lasertherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/33 (0%)		0/33 (0%)
Serious Adverse Events
	Sham Comparator: Sham Lasertherapy		Active Comparator: Lasertherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/33 (0%)		0/33 (0%)
Other (Not Including Serious) Adverse Events
	Sham Comparator: Sham Lasertherapy		Active Comparator: Lasertherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/33 (0%)		0/33 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.