Sphenopalatine Ganglion Stimulation for Ocular and Oral Dryness
Primary Purpose
Dry Eye Disease, Xerostomia
Status
Recruiting
Phase
Not Applicable
Locations
Spain
Study Type
Interventional
Intervention
Osteopathic protocol of Sphenopalatine Ganglion Stimulation
Sponsored by
About this trial
This is an interventional treatment trial for Dry Eye Disease focused on measuring dry eye disease, dryness, osteopathy, Keratoconjunctivitis sicca, Saliva cytokines, Saliva-producing glands, Sjögren´s syndrome, Sphenopalatine ganglion, Tear-producing glands, Tear cytokines, Tear film, Xerostomia
Eligibility Criteria
Inclusion Criteria:
- > 18 years old.
- Patients diagnosed with Dry eye disease (DED) and suffering symptoms of ocular and oral dryness for at least 6 months.
- "Dry eye" symptoms must have a score of > 2 (0-4 range) in mSIDEQ questionnaire.
- Ocularly symptomatic patients (OSDI > 12) despite the medication, medical devices and/or therapeutic measures carried out until the inclusion.
- Symptomatic patients in terms of oral dryness (XI-Sp > 11) despite the medication, medical devices and/or therapeutic measures carried out until the inclusion.
- Schirmer I test, without topical anesthesia, must have an initial value of ≥ 1 mm and <10 mm.
- Not included in any other clinical pharmacological trial or study (medical devices are excluded) in the last 3 months.
- Signed informed consent and ability to complete all study visits.
Exclusion Criteria:
- Irreversible anatomical alteration of the lacrimal glands (watery, sebaceous or mucinic) or salivary, surgeries or by healing processes that affect eyelids and/or conjunctiva.
- Alteration in the autonomic nervous system.
- Another active ocular surface disease different from that caused by DED.
- Oral diseases, inflammations or acute injuries in the mouth (trauma, surgical intervention, etc.) in the last month or healing processes of the oral mucosa.
- Use of cyclosporine or topical tacrolimus started within < 3 months and/or steroids or blood derivatives started within < 1 month and that will not be maintained during the study.
- Use of orally drugs with exocrine hyposecretory side effects or that may affect the parasympathetic nervous system, unless the dose is stable during the previous month to inclusion and whose dose is not expected to vary throughout this study.
- Patients may be using any other medication, topical or systemic, unless the dose are the same for the duration of the study.
- Patients may be using artificial tears, moisturizers in general or blood derivatives, unless the dose was the same in the last month and has to be maintained at the same dose for the duration of the study.
- To have had any "in-office" method to manage DED or Meibomian gland dysfunction (pulsed light, thermal massages, etc.) in the last 6 months.
- Occlusion of the lacrimal puncta in the last month.
- Local (in cranial sphere) or general anesthesia in the last 3 months.
- Use of contact lenses, unless they stop using them for at least one week before inclusion and one week before each visit
Sites / Locations
- IOBARecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Other
Other
Other
Arm Label
Mild dry eye disease
Moderate dry eye disease
Severe dry eye disease
Arm Description
Osteopathic protocol of sphenopalatine ganglion stimulation
Osteopathic protocol of sphenopalatine ganglion stimulation
Osteopathic protocol of sphenopalatine ganglion stimulation
Outcomes
Primary Outcome Measures
Ocular Surface Disease Index (OSDI)
Score value 0-48, where higher score means a worse outcome.
Ocular Surface Disease Index (OSDI)
Score value 0-48, where higher score means a worse outcome.
Modified Single-Item Score Dry Eye-Questionnaire (mSIDEQ)
Score value 0-28, where higher score means a worse outcome
Modified Single-Item Score Dry Eye-Questionnaire (mSIDEQ)
Score value 0-28, where higher score means a worse outcome
Visual analogue Scale (VAS)
Unique measurements 0-10, where higher score means a worse outcome
Visual analogue Scale (VAS)
Unique measurements 0-10, where higher score means a worse outcome
Change in Dry Eye Symptoms Questionnaire (CDES-Q)
First question compares how the patient is at the moment compared with last session in terms of "Equal", "Better" or "Worse". If better or worse is chose, two more questions measure how much improvement or worsening from a 0-10 scale, where higher score means a worse outcome.
Change in Dry Eye Symptoms Questionnaire (CDES-Q)
First question compares how the patient is at the moment compared with last session in terms of "Equal", "Better" or "Worse". If better or worse is chose, two more questions measure how much improvement or worsening from a 0-10 scale, where higher score means a worse outcome.
Statistically significant amelioration in oral symptoms
Enhancement in Xerostomia Inventory Spanish version (XI-Sp) test score 0-11, where higher score means a worse outcome.
Statistically significant amelioration in oral symptoms
Enhancement in Xerostomia Inventory Spanish version (XI-Sp) test score 0-11, where higher score means a worse outcome.
Statistically significant improvement in tear secretion
Schirmer I test, which test score is 0-35 mm, where lower score means a worse outcome.
Statistically significant improvement in tear secretion
Schirmer I test, which test score is 0-35 mm, where lower score means a worse outcome.
Statistically significant improvement in salivary discharge
Salivary flow rate, where flow rate below 0,1ml flow is considered hyposalivation.
Statistically significant improvement in salivary discharge
Salivary flow rate, where flow rate below 0,1ml flow is considered hyposalivation.
Secondary Outcome Measures
Decrease in tear collection time
Statistically significant improvement in tear collection time, using a microcapillar of 1μl.
Increased salivary flow rate
Statistically significant increased salivary flow rate, using Modified Fox Sreebny Technique.
Lipiflow interferometry - lipid layer thickness
Statistically significant improvement in lipid layer thickness using Interferometry with Lipiview.
Lipiflow interferometry - incomplete blink rate
Statistically significant improvement in incomplete blink rate using Interferometry with Lipiview.
Lipiflow interferometry - c-factor
Statistically significant improvement in c-factor, using Interferometry with Lipiview.
Enhancement in Break-Up Time Test
Statistically significant enhancement in Break-Up Time Test (normal >7 seconds) where lower score means a worse outcome.
Corneal Staining
Statistically significant enhancement in Corneal Staining, using Oxford Scale and Cornea and Contact Lens Research Unit (CCLRU) Scale, score 0-5 where higher scores means worse outcome.
Significant beneficial change in molecules evaluated in tear or saliva
The following putative salivary indicators of pain are assayed by enzyme-linked immunosorbent assay (ELISA): Cortisol (DRG Salivary Cortisol ELISA (DRG Instruments GmbH, Marburg, Germany), testosterone (DRG Instruments GmbH), sTNFαRII (Quantikine, Human sTNF RII/TNFRSF1B Immunoassay, R&D Systems, Minneapolis, MN, USA). sAA is
Full Information
NCT ID
NCT05187533
First Posted
October 28, 2021
Last Updated
March 10, 2023
Sponsor
Instituto Universitario de Oftalmobiología Aplicada (Institute of Applied Ophthalmobiology) - IOBA
1. Study Identification
Unique Protocol Identification Number
NCT05187533
Brief Title
Sphenopalatine Ganglion Stimulation for Ocular and Oral Dryness
Official Title
Efficacy of the Sphenopalatine Ganglion Stimulation Osteopathic Protocol in Patients With Ocular and Oral Dryness
Study Type
Interventional
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 15, 2022 (Actual)
Primary Completion Date
May 31, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Instituto Universitario de Oftalmobiología Aplicada (Institute of Applied Ophthalmobiology) - IOBA
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Dry Eye Disease (DED) is a multifactorial pathology characterized by inflammation of the lacrimal functional unit that develops in ocular surface pathology, severely affecting patients quality of life. The core of the treatment relies at present in antinflammatory topical therapies, which are still scarce.
The investigators hypothesize that osteopathy-based techniques may help these patients by influencing the central involvement regarding parasympathetic innervation of tear and saliva-secreting glands.
The aim of this osteopathic treatment protocol is to release the involved structures in the tear-secreting system innervation, such as the sphenopalatine ganglion. In addition, this ganglion innervates the minor salivary glands, therefore it is intended to help patients suffering from xerostomia.
The hypothesis then is that a systemic protocol treatment can help balance both parts of the vegetative nervous system (sympathetic and parasympathetic) with the objective of increasing the secretion of tear and saliva in patients with ocular and oral dryness (DED and xerostomia, respectively), thus improving their clinical situation.
This osteopathic protocol does not have the potential to cause adverse effects. The main objective is to analyze the efficacy of this protocol application in terms of improving symptoms and signs of ocular and oral dryness, tear film quality and inflammation molecule levels in tears and saliva.
Detailed Description
This clinical study intended to offer an alternative therapeutic tool for a disease, dry eye, that is highly prevalent, causes a decreased in the quality of life and work productivity, and whose pharmacologic treatment is very limited.
The osteopathy protocol consists of an initial assessment of the cranial vault and 7 techniques through which the different structures involved are treated and are as follows: 1) balance of the cranio-sacral system; 2) reharmonization of sphenobasilar synchondrosis; 3) and 4) release of the bony components in the pterygo-palatine fossa (maxillas and sphenoid); 5) and 6) release of the bony components in relation with the main lacrimal gland (frontal and front-malar suture); and 7) sphenopalatine ganglion stimulation. The patient is always in supine position and the investigator is standing on the side.
The proposed osteopathy protocol is innocuous, with no possible adverse effects. The main objective is to analyze the efficacy of this protocol application in terms of improving symptoms and signs of ocular and oral dryness, tear film quality and inflammation molecule levels in tears and saliva.
Recruited patients will have dry eye disease (and subsequently ocular dryness) and oral dryness (xerostomia). Inclusion/exclusion criteria are detailed in the corresponding section below, as well as all outcome measures.
All COVID19-related sanitary regulations will be strictly followed.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dry Eye Disease, Xerostomia
Keywords
dry eye disease, dryness, osteopathy, Keratoconjunctivitis sicca, Saliva cytokines, Saliva-producing glands, Sjögren´s syndrome, Sphenopalatine ganglion, Tear-producing glands, Tear cytokines, Tear film, Xerostomia
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
45 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Mild dry eye disease
Arm Type
Other
Arm Description
Osteopathic protocol of sphenopalatine ganglion stimulation
Arm Title
Moderate dry eye disease
Arm Type
Other
Arm Description
Osteopathic protocol of sphenopalatine ganglion stimulation
Arm Title
Severe dry eye disease
Arm Type
Other
Arm Description
Osteopathic protocol of sphenopalatine ganglion stimulation
Intervention Type
Other
Intervention Name(s)
Osteopathic protocol of Sphenopalatine Ganglion Stimulation
Intervention Description
Sphenopalatine Ganglion Stimulation to improve lacrimal and salivary gland secretion to improve ocular and oral dryness
Primary Outcome Measure Information:
Title
Ocular Surface Disease Index (OSDI)
Description
Score value 0-48, where higher score means a worse outcome.
Time Frame
6 Weeks
Title
Ocular Surface Disease Index (OSDI)
Description
Score value 0-48, where higher score means a worse outcome.
Time Frame
18 Weeks
Title
Modified Single-Item Score Dry Eye-Questionnaire (mSIDEQ)
Description
Score value 0-28, where higher score means a worse outcome
Time Frame
6 Weeks
Title
Modified Single-Item Score Dry Eye-Questionnaire (mSIDEQ)
Description
Score value 0-28, where higher score means a worse outcome
Time Frame
18 Weeks
Title
Visual analogue Scale (VAS)
Description
Unique measurements 0-10, where higher score means a worse outcome
Time Frame
6 Weeks
Title
Visual analogue Scale (VAS)
Description
Unique measurements 0-10, where higher score means a worse outcome
Time Frame
18 Weeks
Title
Change in Dry Eye Symptoms Questionnaire (CDES-Q)
Description
First question compares how the patient is at the moment compared with last session in terms of "Equal", "Better" or "Worse". If better or worse is chose, two more questions measure how much improvement or worsening from a 0-10 scale, where higher score means a worse outcome.
Time Frame
6 Weeks
Title
Change in Dry Eye Symptoms Questionnaire (CDES-Q)
Description
First question compares how the patient is at the moment compared with last session in terms of "Equal", "Better" or "Worse". If better or worse is chose, two more questions measure how much improvement or worsening from a 0-10 scale, where higher score means a worse outcome.
Time Frame
18 Weeks
Title
Statistically significant amelioration in oral symptoms
Description
Enhancement in Xerostomia Inventory Spanish version (XI-Sp) test score 0-11, where higher score means a worse outcome.
Time Frame
6 Weeks
Title
Statistically significant amelioration in oral symptoms
Description
Enhancement in Xerostomia Inventory Spanish version (XI-Sp) test score 0-11, where higher score means a worse outcome.
Time Frame
18 Weeks
Title
Statistically significant improvement in tear secretion
Description
Schirmer I test, which test score is 0-35 mm, where lower score means a worse outcome.
Time Frame
6 Weeks
Title
Statistically significant improvement in tear secretion
Description
Schirmer I test, which test score is 0-35 mm, where lower score means a worse outcome.
Time Frame
18 Weeks
Title
Statistically significant improvement in salivary discharge
Description
Salivary flow rate, where flow rate below 0,1ml flow is considered hyposalivation.
Time Frame
6 Weeks
Title
Statistically significant improvement in salivary discharge
Description
Salivary flow rate, where flow rate below 0,1ml flow is considered hyposalivation.
Time Frame
18 Weeks
Secondary Outcome Measure Information:
Title
Decrease in tear collection time
Description
Statistically significant improvement in tear collection time, using a microcapillar of 1μl.
Time Frame
18 Weeks
Title
Increased salivary flow rate
Description
Statistically significant increased salivary flow rate, using Modified Fox Sreebny Technique.
Time Frame
18 Weeks
Title
Lipiflow interferometry - lipid layer thickness
Description
Statistically significant improvement in lipid layer thickness using Interferometry with Lipiview.
Time Frame
18 Weeks
Title
Lipiflow interferometry - incomplete blink rate
Description
Statistically significant improvement in incomplete blink rate using Interferometry with Lipiview.
Time Frame
18 Weeks
Title
Lipiflow interferometry - c-factor
Description
Statistically significant improvement in c-factor, using Interferometry with Lipiview.
Time Frame
18 Weeks
Title
Enhancement in Break-Up Time Test
Description
Statistically significant enhancement in Break-Up Time Test (normal >7 seconds) where lower score means a worse outcome.
Time Frame
18 Weeks
Title
Corneal Staining
Description
Statistically significant enhancement in Corneal Staining, using Oxford Scale and Cornea and Contact Lens Research Unit (CCLRU) Scale, score 0-5 where higher scores means worse outcome.
Time Frame
18 Weeks
Title
Significant beneficial change in molecules evaluated in tear or saliva
Description
The following putative salivary indicators of pain are assayed by enzyme-linked immunosorbent assay (ELISA): Cortisol (DRG Salivary Cortisol ELISA (DRG Instruments GmbH, Marburg, Germany), testosterone (DRG Instruments GmbH), sTNFαRII (Quantikine, Human sTNF RII/TNFRSF1B Immunoassay, R&D Systems, Minneapolis, MN, USA). sAA is
Time Frame
18 Weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
> 18 years old.
Patients diagnosed with Dry eye disease (DED) and suffering symptoms of ocular and oral dryness for at least 6 months.
"Dry eye" symptoms must have a score of > 2 (0-4 range) in mSIDEQ questionnaire.
Ocularly symptomatic patients (OSDI > 12) despite the medication, medical devices and/or therapeutic measures carried out until the inclusion.
Symptomatic patients in terms of oral dryness (XI-Sp > 11) despite the medication, medical devices and/or therapeutic measures carried out until the inclusion.
Schirmer I test, without topical anesthesia, must have an initial value of ≥ 1 mm and <10 mm.
Not included in any other clinical pharmacological trial or study (medical devices are excluded) in the last 3 months.
Signed informed consent and ability to complete all study visits.
Exclusion Criteria:
Irreversible anatomical alteration of the lacrimal glands (watery, sebaceous or mucinic) or salivary, surgeries or by healing processes that affect eyelids and/or conjunctiva.
Alteration in the autonomic nervous system.
Another active ocular surface disease different from that caused by DED.
Oral diseases, inflammations or acute injuries in the mouth (trauma, surgical intervention, etc.) in the last month or healing processes of the oral mucosa.
Use of cyclosporine or topical tacrolimus started within < 3 months and/or steroids or blood derivatives started within < 1 month and that will not be maintained during the study.
Use of orally drugs with exocrine hyposecretory side effects or that may affect the parasympathetic nervous system, unless the dose is stable during the previous month to inclusion and whose dose is not expected to vary throughout this study.
Patients may be using any other medication, topical or systemic, unless the dose are the same for the duration of the study.
Patients may be using artificial tears, moisturizers in general or blood derivatives, unless the dose was the same in the last month and has to be maintained at the same dose for the duration of the study.
To have had any "in-office" method to manage DED or Meibomian gland dysfunction (pulsed light, thermal massages, etc.) in the last 6 months.
Occlusion of the lacrimal puncta in the last month.
Local (in cranial sphere) or general anesthesia in the last 3 months.
Use of contact lenses, unless they stop using them for at least one week before inclusion and one week before each visit
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Andrea Ramos, PT
Phone
983184734
Email
andrearamosfisio@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Francisco Blazquez, MD
Email
blazquez@ioba.med.uva.es
Facility Information:
Facility Name
IOBA
City
Valladolid
ZIP/Postal Code
47011
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andrea Ramos, PT
Phone
983184734
Email
andrearamosfisio@gmail.com
First Name & Middle Initial & Last Name & Degree
Francisco Blazquez, MD
Email
blazquez@ioba.med.uva.es
First Name & Middle Initial & Last Name & Degree
Eva Sobas Abad, PhD
First Name & Middle Initial & Last Name & Degree
Margarita Calonge, MD, PhD
First Name & Middle Initial & Last Name & Degree
Amaia Iturburu, MD, PhD
First Name & Middle Initial & Last Name & Degree
Andrea Ramos, PT
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Sphenopalatine Ganglion Stimulation for Ocular and Oral Dryness
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