Efficacy of Zinc on Concurrent Chemo-radiotherapy Induced Taste Alterations
Condition: Taste, Altered
MeSH terms: Dysgeusia
Study type: Interventional
Phase: Phase 3

Summary: 
      Taste changes are common in cancer patients receiving concurrent chemoradiation which become
      a significant complaint and a cause of distress and morbidity. Loss of gustatory function
      further advances to malnutrition, weight loss, reduced quality of life, poor compliance and
      even diminished response to drug therapy. Taste is an essential sensation which serves oral
      intake of food and enables to prevent the ingestion of potentially harmful and poisonous
      substances. The sense of taste is crucial for an individual's well-being and psychological
      health. Taste changes may advance to reduced appetite, dietary insufficiency, food repulsion
      affecting body weight and anorexia further leading to impaired immunity, decline in health
      status and malnutrition. As taste impairment is not a life-threatening event therefore it
      might not be reported by some patients. Hence, this aspect is neglected despite being a
      common and distressing side-effect of chemoradiation. Due to the location of the cancer and
      the long-term effects of cancer therapies, patients with oral cavity cancers have a specially
      high prevalence of chemosensory disorders. Zinc is comparatively non-toxic if taken orally,
      and rather non-toxic in contrast to other trace metals such as manganese and iron. Zinc is an
      integral element in both the maintenance and repair of taste buds. It is involved in
      promoting the diffusion of taste stimuli to taste buds. Salivary zinc has been found in
      association with Gustin (carbonic anhydrase, CA VI), a zinc-metalloprotein enzyme that may be
      involved with providing nutrition to the human taste buds. Zinc influences the synthesis of
      gustin required for the growth, development, maintenance and production of taste buds and
      regulation of taste function.

      The hypothesis was:

      Null hypotheses: There is no difference in the taste acuity between test and control group
      with the administration of zinc sulfate.

      Alternative hypotheses: There is a difference in the taste acuity between test and control
      group with the administration of zinc sulfate.

      Thus, the present study aimed to observe changes in taste function of oral cancer patients by
      detection and recognition thresholds before beginning their treatment (before chemoradiation
      and intervention), at the end of chemoradiation and a month after and to evaluate the
      preventive effect of zinc sulfate on chemoradiation-induced taste changes. To the best of our
      knowledge, similar study has not been conducted before in our region.
    

Detailed description: 
      Consecutive Sampling was used. It was a two-stage sampling method. Data was collected from
      patients visiting the Oncology Section at Atomic Energy Medical Centre Karachi from September
      2017 to March 2018 on a proforma after being examined by the section head oncologist for the
      tumor. A standard proforma was used to record the taste acuity of the participants.
      Furthermore, the proforma also had details about patient's site of tumor, stage of tumor,
      daily fraction of dose, total dose of radiotherapy, chemotherapeutic drug and duration of the
      treatment for the record.

      The international Standard Organization ISO 3972:2011/Cor 1:2012 provides guidelines for
      Method of investigating sensitivity of taste. Therefore, all solutions were prepared in
      accordance with the ISO. The solutions were prepared with deionized water in grams/litre and
      stored in 1000ml glass bottles at room temperature. All solutions were colorless and
      odorless. Eight increasing concentration of each taste (salty, sweet, sour and bitter;
      altogether 32 bottles), zinc capsules and placebo (filled with cornstarch) were prepared by
      ATCO pharmaceuticals. Sodium chloride was used as a stimulus for salty, sucrose for sweet,
      citric acid for sour and caffeine for bitter.

      Patients were instructed to refrain from eating or drinking 30 mins to 1 hour before the
      procedure. If any patient was wearing denture it was taken off before the procedure and mouth
      was thoroughly rinsed with water before each trial. Each subject was given single 15ml of
      each solution in a cup and asked to hold the solution for 30 seconds in their mouth and
      gargle out to make sure the whole of oral cavity will be exposed to the taste solution (sip
      and spit procedure). After each presentation, patient mouth was thoroughly rinsed with water
      to remove any after taste and to avoid the residual effect of the previous taste solution.
      The water used for rinsing was identical with that used for preparing solutions. Each trial
      was spaced at least 15 seconds apart. The time spent for each data collection tool was 20-30
      mins.

      Taste function of each patient for four basic taste (salty, sweet, sour and bitter) was
      assessed by detection and recognition threshold which were noted on a proforma. The proforma
      had three columns (baseline, end chemoradiation and follow-up a month after chemoradiation)
      for each taste and marking from 1 to 8 corresponding to the increasing concentration of the
      taste solutions (D8-D1) for each taste. D1 was considered as the highest concentration
      whereas D8 was the lowest concentration of each taste solution.

      The cut-off values that were set for each patient for detection and recognition threshold
      were:

      1-8 = able to identify and recognize the taste 0 = unable to identify and recognize any
      response For Detection threshold (DT) A sample of deionized water and a taste sample was
      presented to the patient. The order of presentation was randomized for every subject.
      Participants were asked to indicate which of the sample contains the taste. Detection
      threshold (DT) was considered as the lowest level at which a subject can perceive a stimulus.
      This was the minimum concentration at which the subject can detect that there is something
      different from water, but may not identify its quality. D1 was the highest concentration of
      solution for each taste and was marked on proforma as 1 and D8 was the minimum concentration
      and was marked as 8.

      For Recognition threshold (RT) Participants were also asked to describe the taste of the
      solution either salty, sweet, sour or bitter. Recognition threshold was considered as the
      lowest level of a solution at which a subject can correctly recognize its taste, i.e.,
      sucrose for sweet, sodium chloride (NaCl) for salty, citric acid for sour and caffeine for
      bitter. D1 was the highest concentration of solution for each taste and was marked as 1
      whereas D8 was the minimum concentration and was marked as 8.

      Solutions were presented in the increasing order of their concentration and the lowest
      concentration of solution was marked for each taste that was perceived by the patient. Any
      subject who was unable to detect the difference between the water and the tastant, the
      concentration of the taste solution was increased.

      Data was entered and analyzed by the IBM SPSS software for windows version 20. Data is shown
      as mean ± SD for descriptive statistics and as median [IQR] for intervention statistics.
      First, the normality was assessed of all four taste variables by Shapiro-Wilk test. The
      normality tests are given below.

      The baseline characteristics of the test and control group were compared by Chi square and
      independent t test. To observe difference within the two groups, Wilcoxon Signed Ranks test
      was applied. To observe the difference between the two groups, Mann-Whitney U test was used.
      P-value was calculated by Friedman test. Statistical significance was accepted at P < 0.05.
    

Intervention name(s): Placebo oral Zinc capsule; Zinc Sulfate 220 MG
Intervention type(s): Drug; Drug
Intervention description(s): Look alike cap of corn starch as a placebo of Zinc to be given on day 1 of chemo-radiotherapy; Zinc sulfate in test group dose was 220 mg which is equivalent to 50 mg of elemental zinc
Other intervention name(s): Corn Starch; Zincat
Intervention MeSH terms: Zinc; Zinc Sulfate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Taste alterations; zinc sulfate; oral cancer; taste acuity