EVADRY® in the Treatment of Xerostomia in Sjögren's Syndrome (DRYLESS)

DRYLESS: Randomized Controlled Trial of EVADRY® vs Placebo in the Treatment of Xerostomia in Sjögren's Syndrome

Xerostomia is a common and very bothersome manifestation that impairs the quality of life in Sjogren's syndrome. Symptomatic therapeutic alternatives for this syndrome are limited in Tunisia. We resort to bromhexine off-label with low efficacy. The aim of this work is to demonstrate the superiority of a treatment based on dietary supplements (EVADRY) vs placebo in the treatment of xerostomia. This is a double-blind randomized clinical trial with 2 arms: an EVADRY arm (n=90) and a placebo arm (n=90). The primary outcome measure is a 35% increase in salivary flow after 3 months. Secondary outcome measures were based on the Oral Health Impact Profile questionnaire, Xerostomia Inventory, the HAD depression scale, and the buccal Schirmer test.

Study Overview

• Status: Not yet recruiting
• Conditions: Sjogren's Syndrome
• Intervention / Treatment: Dietary supplement: EVADRY; Other: Placebo

Detailed Description

Study design:

This is a randomized controlled double-blind clinical trial involving 2 groups:

• Group 1: consisting of 90 patients receiving the EVADRY dietary supplement treatment.
• Group 2: consisting of 90 patients receiving a placebo

Inclusion and exclusion criteria:

• Inclusion criteria:

The included patients meet the following criteria:

• age over 18 years
• diagnosis of Sjogren's syndrome according to ACR/EULAR 2016 criteria
• continuous xerostomia for more than 3 months

• initial salivary flow rate < 0.1 ml/min

  • Non-inclusion criteria:

• allergy or hypersensitivity to any of the products
• pregnancy
• breastfeeding
• oral or throat surgery before wound healing

• cognitive or dementia disorders

  • Exclusion criteria:

These include:

• Occurrence of cognitive or dementia disorders
• Pregnancy
• Allergy to any of the components of the EVADRY product
• Indication of oral or throat surgery

Randomization:

This is a randomization by random blocks. A co-investigator (who is not in contact with the patients) will be responsible for this randomization. The EVADRY treatment and the placebo will have the same packaging. Codes will be assigned to the sprays by the investigator responsible for the randomization. These codes will be placed in sealed envelopes and will only be opened at the end of the study. They will be kept by another investigator who has no knowledge of the randomization.

Treatment and interventions:

The EVADRY oral spray and the placebo are produced by Wellnet laboratory.

• EVADRY spray: It is a phytotherapy-based medication in the form of an oral spray. It is a 100 ml bottle containing ALEO BARBADENSIS LEAF WATER (1 ml), Chamomilla Recutita Flower extract (30 mg), TOCOPHEROL (10 mg), hyaluronic acid (2 mg), mentha spicata herb oil (10 mg), and eugenol (40 µg).

• The placebo corresponds to flavored water (mint extract) with the same taste as EVADRY. It is placed in a bottle with the same appearance as EVADRY.

Both products are administered at a rate of 5 intra-oral sprays per day.

Evaluation criteria:

• Primary evaluation criterion: It is based on the measurement of salivary flow rate (SFR). It consists of asking the patient to collect their saliva in the morning without prior stimulation (no smoking, chewing gum, or alcohol one hour before) in a graduated tube for 15 minutes. The patient should be comfortably seated with their head slightly tilted forward and their mouth open to allow saliva to flow. A value less than 0.1 ml/minute corresponds to hyposalivation.

• Secondary evaluation criteria:

• Xerostomia Inventory in French version: it is a questionnaire composed of 11 questions. For each item, there is an evaluation of its frequency (never, rarely, occasionally, quite often, very often). The total score ranges from 11 to 55 points.
• OHIP-14 questionnaire: it includes 7 dimensions with 14 items to assess quality of life. The higher the score on this questionnaire, the more negative the impact on quality of life.
• HAD scale: it is an instrument that allows screening for anxiety and depressive disorders. It consists of 14 items rated from 0 to 3 : 7 for anxiety and 7 for depression. We will have 2 scores. A score ≤7 corresponds to the absence of symptoms, ≥11 corresponds to definite symptomatology, and between the two, it is doubtful.
• Buccal Schirmer test: it consists of a strip of Whatman paper (blotting paper) placed in a polyethylene bag, with the first 5 mm of the strip protruding from one end of the bag. This end is then folded and placed under the patient's tongue in contact with the floor of the mouth for 5 minutes. The patient should be in a forward-leaning position, hands on knees, and eyes closed. After five minutes, the strip is removed and the soaked portion is measured in centimeters.

Patient follow-up:

The patients will be interviewed and examined initially. During this consultation, the patient's epidemiological and clinical data will be collected. During the same consultation, SFR and buccal Schirmer test will be measured, and Xerostomia Inventory, OHIP-14, and HAD will be calculated.

These tests will be repeated at 1, 2, and 3 months.

Interruption and end of the trial:

Patient follow-up is planned for 3 months. The statistical study is planned for 1 month.

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Fatma Saïd; Phone Number: 0021671150876; Email: saidzribifatma@yahoo.fr
• Study Contact Backup: Name: Fatma Saïd; Email: saidzribifatma@yahoo.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• age over 18 years
• diagnosis of Sjogren's syndrome according to ACR/EULAR 2016 criteria
• continuous xerostomia for more than 3 months
• initial salivary flow rate < 0.1 ml/min

Exclusion Criteria:

• Occurrence of cognitive or dementia disorders
• Pregnancy
• Allergy to any of the components of the EVADRY product
• Indication of oral or throat surgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EVADRY; 90 Sjogren's syndrom patients with objective xerostomia receiving the EVADRY dietary supplement treatment.	Dietary supplement: EVADRY; The EVADRY oral spray and the placebo are produced by Wellnet laboratory. • EVADRY spray: It is a phytotherapy-based medication in the form of an oral spray. It is a 100 ml bottle containing ALEO BARBADENSIS LEAF WATER (1 ml), Chamomilla Recutita Flower extract (30 mg), TOCOPHEROL (10 mg), hyaluronic acid (2 mg), mentha spicata herb oil (10 mg), and eugenol (40 µg).
Placebo Comparator: PLACEBO; 90 Sjogren's syndrom patients with objective xerostomia receiving a placebo.	Other: Placebo; The placebo corresponds to flavored water (mint extract) with the same taste as EVADRY. It is placed in a bottle with the same appearance as EVADRY. Both products are administered at a rate of 5 intra-oral sprays per day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
salivary flow rate (SFR)	It consists of asking the patient to collect their saliva in the morning without prior stimulation (no smoking, chewing gum, or alcohol one hour before) in a graduated tube for 15 minutes. The patient should be comfortably seated with their head slightly tilted forward and their mouth open to allow saliva to flow. A value less than 0.1 ml/minute corresponds to hyposalivation.	at inclusion, after 1, 2 and 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Xerostomia Inventory in French version	it is a questionnaire composed of 11 questions. For each item, there is an evaluation of its frequency (never, rarely, occasionally, quite often, very often). The total score ranges from 11 to 55 points	at inclusion, after 1, 2 and 3 months
Oral Health-related quality of life (OHIP-14) questionnaire	it includes 7 dimensions with 14 items to assess quality of life. The higher the score on this questionnaire, the more negative the impact on quality of life	at inclusion, after 1, 2 and 3 months
Hospital anxiety and depression (HAD) scale	it is an instrument that allows screening for anxiety and depressive disorders. It consists of 14 items rated from 0 to 3 : 7 for anxiety and 7 for depression. We will have 2 scores. A score ≤7 corresponds to the absence of symptoms, ≥11 corresponds to definite symptomatology, and between the two, it is doubtful	at inclusion, after 1, 2 and 3 months
Buccal Schirmer test	it consists of a strip of Whatman paper (blotting paper) placed in a polyethylene bag, with the first 5 mm of the strip protruding from one end of the bag. This end is then folded and placed under the patient's tongue in contact with the floor of the mouth for 5 minutes. The patient should be in a forward-leaning position, hands on knees, and eyes closed. After five minutes, the strip is removed and the soaked portion is measured in centimeters.	at inclusion, after 1, 2 and 3 months

Collaborators and Investigators

• Sponsor: University Tunis El Manar
• Investigators: Study Chair: Ines Naceur, Centre Hospitalo-Universitaire La Rabta; Study Chair: Tayssir Ben Achour, Centre Hospitalo-Universitaire La Rabta; Study Chair: Mayssam Jridi, Centre Hospitalo-Universitaire La Rabta; Study Director: Monia Smiti, Centre Hospitalo-Universitaire La Rabta

Study record dates

Study Major Dates

• Study Start (Estimated): April 15, 2024
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: March 2, 2024
• First Submitted That Met QC Criteria: March 14, 2024
• First Posted (Actual): March 15, 2024

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 14, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: treatment; xerostomia; sjogren's syndrom
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Eye Diseases; Disease; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Stomatognathic Diseases; Mouth Diseases; Lacrimal Apparatus Diseases; Arthritis, Rheumatoid; Salivary Gland Diseases; Dry Eye Syndromes; Syndrome; Sjogren's Syndrome; Xerostomia
• Other Study ID Numbers: DRYLESS1; CHU La Rabta (Other Identifier: La Rabta hospital)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: all investigators work in the same department

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No