Drug-induced Xerostomia. Evaluation of Malic Acid 1%, Salivary Mucins and Buffering Capacity
Condition: Xerostomia; Depression; Hypertension
MeSH terms: Xerostomia
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      The aim of our study was to evaluate the clinical efficacy of a topical sialogogue spray
      containing 1% malic acid on patients affected by xerostomia caused by drugs.

      This research took the form of a double-blind, randomized clinical trial at Faculty of
      Dentistry of University of Granada (Spain). Participants with antidepressant-induced and
      antihypertensive-induce xerostomia were divided into two groups: for the first 'intervention
      group' a topical sialogogue spray (1% malic acid) was applied, while for the second 'control
      group', a placebo spray was applied; for both groups the sprays were applied on demand during
      two weeks. The Dry Mouth Questionnaire (DMQ) was used to evaluate xerostomia levels before
      and after product/placebo application. Unstimulated and stimulated salivary flows rates,
      before and after application, were measured.
    

Detailed description: 
      - Patients and study Design The study was approved by the University of Granada Research
      Ethics Committee (Spain). All measurements and interventions were undertaken with the
      understanding and written consent of each participant according to Helsinki II Agreement.The
      study was designed as a double-blind randomized clinical trial following guidelines
      established by The Consort Statement (http://www.consort-statement.org/consort-statement/).
      All study participants were recruited from the Faculty of Dentistry of the University of
      Granada (Spain)at Drug Interactions in Dentistry clinical practice, between September and
      December 2011. Recruitment was supervised by research assistants.

      All participants had a full medical history and saliva samples were collected at the Faculty
      of Dentistry of University of Granada (Spain) at the Pharmacological Investigation in
      Dentistry Research Group laboratory (CTS-654).

      Sample size determination was based on the standard deviation of the main variable: the Dry
      Mouth Questionnaire (DMQ)was tested to determine the minimum sample size necessary to
      reliably confirm the hypothesis that a topical 1% malic acid sialogogue spray, combined with
      xylitol and fluoride, is effective for the treatment of xerostomia induced by antidepressant
      drugs over a two-week period. DMQ and saliva collection were measured the same day and by the
      same investigator.

        -  Clinical Intervention Once the participants had signed the informed consent form and
           anamnesis had been carried out, the following question was asked to every patient: "How
           often do you feel dry mouth?" Available answers were: "never", "sometimes", "usually" or
           "always." Those who answered "usually" or "always" were considered as suffering from
           xerostomia. Our clinical intervention among the intervention group subjects was the
           delivery to the patients of a topical sialogogue, containing 1% malic acid, xylitol 10%
           and fluoride0.05%(Xeros Dentaid Spray©, Dentaid, Barcelona, Spain) for two weeks,
           whereas a control group was given a placebo with the same presentation and composition
           (excepting 1% malic acid). Randomization was performed using the website
           http://www.randomization.com, obtaining a randomization plan, which assigned
           participants to either the intervention group or the control group. This randomization
           plan was delivered to a person unrelated to the study in order to prevent both
           participants and researchers from identifying the product.Both sprays were transferred
           by foreign personnel into two identical opaque flasks(without any brand name)labeled A
           and B containing respectively, either 1% malic acid or placebo.A code for randomization
           was kept in an opaque envelope in a safe environment and opened only at the end of the
           study. Data were analyzed by a third party blinded to the allocation results. 1% malic
           acid/placebo sprays were applied on demand, with a maximum of eight doses per day. No
           participants left the trial.

        -  Dry Mouth Questionnaire (DMQ) The DMQ, developed by Vissink et al., Gravenmade et al.,
           van der Reijden et al. and Regelink et al. was used in order to obtain subjective
           information about the severity of xerostomia before and after treatment with malic
           acid/placebo. Every participant answered an initial questionnaire (DMQ 1) about the
           symptoms related to oral dryness, before receiving a spray (1% malic acid or placebo).
           After two weeks of applications, patients had to answer DMQ 1 again as well as an
           additional questionnaire (DMQ 2) about the efficacy of the sprays. Increased DMQ scores
           indicate improvement of xerostomia. DMQ 1 was used to assess the initial severity of
           oral dryness and in particular its impact on oral function: problems when chewing,
           swallowing, speaking and general impact on daily life.

      DMQ 1 used a 0-to-4 rating scale where 0 = "very dry" and 4 = "not dry at all." After two
      weeks of treatment, DMQ 1 was repeated. DMQ 2 was designed to assess the impact of the spray
      on the symptoms of xerostomia, and was also based on a 0-to-4 rating scale where 0 = frequent
      restriction of oral function and 4= no restriction of oral function/no feeling of oral
      dryness. The effect of the frequency and duration of spray applications in the oral cavity
      were also registered.

      - Sialometries As secondary measurements, both unstimulated and stimulated salivary flow
      rates were assessed in all patients. The unstimulated salivary flow rate was obtained by the
      spit method every 30 seconds for 15 minutes. Saliva was collected in 20 mL plastic
      containers, which were pre-weighted (in 0.001 g) using a precision scale. Measurements were
      expressed as mL/min. Stimulated whole saliva was obtained by chewing a 1 g piece of paraffin
      wax for six minutes. Saliva collected during the first minute was discarded, and then
      collected into the container every 30 seconds. Both DMQ and sialometries were always assessed
      at the same time of day (from 09:00 to 11:00 a.m.) to avoid any circadian variation. Before
      the evaluation, participants were asked not to eat, drink, smoke or brush their teeth for one
      hour prior to their appointment at the clinic.Time passed between the last use of the
      sialogogue and the salivary flow measurements was 6 hours.
    

Intervention name(s): Malic Acid; Placebo
Intervention type(s): Drug; Other
Intervention description(s): Oral spray for application into the oral cavity; Oral spray for application into the oral cavity
Other intervention name(s): XerosDentaid Spray; Flask labeled A; Flask labeled B
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Xerostomia; Antidepressant agents; Antihypertensive agents