Evaluation of an Electro-stimulator for the Treatment of Xerostomia

Safety and Performance Evaluation of an Electro-stimulator Mounted on an Intra-oral Removable Appliance (Saliwell GenNarino) for the Treatment of Xerostomia

This is a multinational trial, aimed at testing the safety and performance of a electrostimulating device ("GenNarino") to treat dry mouth, over one year. The design is as follows:

• Multi-center, double blind, sham (placebo) controlled, about 10 xerostomia patients per center
• Patients receive a GenNarino (and its remote control) that is programmed for one month sham and one month active mode (the order of which is randomly assigned), and thereafter 9 months at the active mode (divided in period of 3 months, the order of each is randomly assigned at wearing GenNarino for 1, 5 or 10 minutes at a time).

Study hypothesis: Gennarino will lead to significant symptomatic improvement

- At the clinic: monthly examinations at the first 2 months, and then every 3 months, including whole saliva collection and questionnaire; at the first visit impression taking for GenNarino preparation

The clinical trial, titled "Safety and performance evaluation of an electro-stimulator mounted on an intra-oral removable appliance (GenNarino) for the treatment of xerostomia" is a prospective, randomized, double-blind, sham-controlled multi-center trial, followed by an open-label study. Study subjects are patients with xerostomia. The purpose of the trial is to test the safety and efficacy of electrostimulation using the GenNarino device.

The primary endpoint is significant symptomatic improvement, and the secondary ones, increased salivary output and event free use (no adverse side-effects). The clinical follow-up consists of periodic clinical examinations.

In this clinical trial the use of the device is compared between active vs. sham mode for one month each in a double-blind design (Stage I). Thereafter, at Stage II the xerostomia relieving effect of the active device is assessed in an open label design for additional 6 months. Clinic- and home-based questionnaires and whole saliva collections are performed.

Inclusion Criteria:

1. The patient must be at least 18 years of age.

2. The patient must have clinical symptoms of xerostomia (dry mouth) due to

   • Primary or secondary Sjögren's syndrome
   • Medication intake
   • Head and neck radiation with survival expectancy of more than one year
   • Chronic graft vs. host disease with survival expectancy of more than one year

3. Patients are requested not to take systemic sialogogues during the first 2 months of the study (when active is tested vs. sham)

4. Female patients of child bearing potential must have a negative pregnancy test within twenty-four hours of enrollment.

5. The patient must understand and consent in writing to the procedure.

6. The patient agrees to undergo all examinations and clinical evaluations planned for the study.

Exclusion Criteria:

1. Active HIV or HCV infection

2. Severe systemic disease

3. Known allergy to materials similar to be used in the investigational product

4. Known mental disease

5. Presence of depression, by positive answers to both the following questions:

   • "During the past month have you often been bothered by feeling down, depressed or hopeless?"
   • "During the past month have you often been bothered by little interest or pleasure in doing things?"

6. Patients wearing other active implants like pacemaker or defibrillator

7. Patients with poor oral hygiene

8. Patients whose oral anatomical characteristics precludes the insertion of the device

9. Patients who are unable or unwilling to cooperate with study procedures.

10. Pregnancy

11. Presence of erosive or ulcerative oral lesions, which are chronic or recurrent, such as erosive lichen planus, RAS, eryth. Candidosis, and of suspected pre-malignant or malignant lesions