SALRISE, v1
Research type
Research Study
Full title
SALivary electro-stimulation for the treatment of dry mouth in patients with Sjogren's syndrome: a multicentRe randomISEd sham-controlled double-blind study
IRAS ID
223791
Contact name
Stefano Fedele
Contact email
Sponsor organisation
University College London
Clinicaltrials.gov Identifier
Z6364106 2018 03 151, UCL Data Protection Registration Number
Duration of Study in the UK
4 years, 0 months, 30 days
Research summary
Research Summary:
Dry mouth is a common manifestation of primary Sjogren’s syndrome (pSS) affecting speech, swallowing, oral health and quality of life. It is a distressing and persistent condition which can lead to long-lasting oral discomfort, dental infections, diminished quality of life, social isolation and loneliness.Unfortunately, current therapies of dry mouth are often unsatisfactory, only offering transient relief, may be expensive and may result in adverse effects.
A novel intraoral electronic device has recently been developed to treat dry mouth. The device, acting as a “salivary pacemaker”, is taken home by the patient and works by being placed in the mouth as and when needed. It harmlessly releases electrical pulses to stimulate the nerves (electrostimulating) associated with salivary gland secretion. However, the electrical pulse intensity is below the human sensitivity level, therefore it cannot be felt by the patient.
The aim of SALRISE is to determine whether the device reduces dry mouth symptoms in patients with pSS. 130 participants will be randomly assigned to one of two groups. One group will receive an active, electrostimulating device that provides mechanical/tactile stimulation but also releases electrical pulses. The second group will receive a sham device that does not release electricity but provides mechanical/tactile stimulation only. They will be asked to use the device for 12 months.
Neither doctors nor participants will be aware of which devices are functional or sham to ensure that the study results cannot be influenced. Participants will attend 5-6 hospital appointments over 12 months, where they will be asked to complete questionnaires regarding their dry mouth symptoms, oral health, quality of life and use of health services. They will also be asked to do two simple 5-minute tests which require them to spit their saliva
Summary of Results:
Background Primary Sjögren’s syndrome (pSS) is the second most common rheumatic autoimmune disease, after rheumatoid arthritis. A rheumatic autoimmune disease is one where someone’s immune system mistakenly attacks their own body, including their joints, muscles and other parts of the body, and may sometimes lead to extreme fatigue. In the case of pSS the immune system can attack and damage the glands that produce tears in people’s eyes and saliva in their mouths, leaving them with persistent dry eyes and dry mouth. The lack of saliva causes discomfort to the mouth due to the lack of lubrication and can result in problems with speech, eating and swallowing, the health of the teeth and gums, as well as sleep. Treatments to help with the dry mouth symptoms of pSS are limited. They include lozenges (sweets) and gums to chew and try to stimulate saliva production, gels/sprays containing saliva substitutes to help keep the mouth moist, and sometimes medicines that help the body produce more saliva. Unfortunately, these treatments don’t always work well, and may result in unwanted side effects.SALRISE Trial
A medical device has been developed which, when placed into the mouth for short periods, releases a mild and painless electrical pulse. These pulses, which are very mild and therefore not felt, aim to stimulate the nerves associated with salivary production. Early research has shown that the device may increase saliva production and reduce the sensation of dry mouth.
The main purpose of the SALRISE trial was to test an updated version of this device (called a SaliPen) in people with pSS.
In the SALRISE trial we compared two versions of the SaliPen: one that releases an electrical pulse (active SaliPen) and another version of the same device that doesn’t produce any electrical signal (sham SaliPen). Patients who agreed to take part were randomly allocated to be given either the active SaliPen or a sham SaliPen. Both devices looked and felt identical so it was not possible for people to tell which one they had been given.
We asked the participants in our study to use the Salipen device at home as needed for one year to find out whether the device led to an improvement in their dry mouth symptoms and their health-related quality of life. To help us measure this we asked them to complete questionnaires at the start of the trial and several times throughout the year about their dryness symptoms, their quality of life and the impact of dry mouth on daily activities. We also measured how much saliva they produced at the start of the trial and on several occasions throughout the year. In addition, we asked participants whether use of the device led them to use NHS services (e.g. GP or hospital appointments) or medications more or less. This is important should the NHS want to consider recommending use of Salipen in the future. .Impact of COVID-19
About 30% of the participants had completed their involvement in the trial by the time the COVID-19 pandemic began. Participants who were still involved in the trial when the pandemic began were unable to attend their clinic visits in person. However, where possible they were still asked to complete their questionnaires, either by post or by a healthcare professional asking them the questions by phone. However, it was no longer possible to measure the amounts of saliva being produced.What we found out
136 participants with pSS were recruited to the trial: of these, 67 were randomly allocated to use an active SaliPen and 69 a sham SaliPen. The two groups were similar in terms of their personal characteristics such as gender, age, ethnicity, and initial dry mouth symptoms.
At the end of the trial we compared participant responses to the various questionnaires filled out through the course of the year to see whether there was a difference between the two groups. The questionnaires contained 11 questions about how often participants experienced different dryness symptoms, leading to a total score. A lower score would indicate less dryness and a higher score would indicate more dryness. We found that, after one year, the scores had decreased in both groups. This indicated that participants in both groups thought their dryness symptoms had improved. However, although there was an indication that using an active SaliPen might have some short-term benefit, there was no convincing evidence at the end of the year that the active SaliPen improved dry mouth symptoms more than the sham SaliPen.
The questionnaires also included 5 questions that are used to determine the patient’s health-related quality of life. These were included to assess any additional benefits that patients may perceive which are not fully captured when focusing only on the symptoms of dry mouth. This includes things like pain, discomfort, anxiety, depression and any perceived problems with mobility, self-care or routine activities such as work. During the course of the year, we found that participants were slightly better off in terms of their quality of life if they had been allocated to the active Salipen group compared to the sham Salipen group.
We also compared average salivary flow measurements and found an increase in salivary flow over the year in both groups, but unfortunately many planned measurements were not recorded because participants were unable to attend clinic in person due to COVID-19 restrictions. The available data indicates using an active SaliPen might create a short-term improvement in salivary flow but provides no convincing evidence that the active SaliPen increased salivary flow more than the sham Salipen over one year of use.
Finally, we found only very small differences in NHS costs between the two groups. During the course of the year, those using the active Salipen incurred £1,093 of healthcare costs on average compared to £1,162 in the sham Salipen group. However, when the additional cost of the device (£188) is factored in, it is unlikely that there would be any cost savings for the NHS.
There were no reports of notably severe adverse effects during the study. However, about 13% of participants reported some discomfort associated with using SaliPen. This happened regardless of whether they were using the active or sham SaliPen.How has this trial helped patients and researchers?
This trial has helped us understand whether using a SaliPen could help improve dry mouth symptoms of pSS, and whether SaliPen should be recommended for the treatment of pSS in the NHS. It has also highlighted the value to patients of conducting the trial over a year and not just over the short term, as there was no convincing evidence that the possible early benefits were maintained.REC name
East of England - Essex Research Ethics Committee
REC reference
18/EE/0153
Date of REC Opinion
16 Jul 2018
REC opinion
Further Information Favourable Opinion