Chamomile Effect on Xerostomia Associated With End-stage Renal Disease in Elderly

Study Overview
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Brief Summary
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Background and Objectives: Chronic hemodialysis causes changes in blood chemistry as well as dry mouth, due to removal of excess fluids. Dry mouth is due to hyposalivation or change in saliva composition. Many herbal medicines have been used as treatment options. Since the chamomile was suggested as a potent oral moisturizer by previous studies that have been done in this field. Therefore, the investigators decided to assess the effect of chamomile oral rinse on the salivary nitric oxide level, salivary flow rate and salivary pH in elderly patients on chronic hemodialysis. Material and Methods: It is an interventional randomized controlled clinical trial with a biochemical assessment. A chamomile, and placebo mouthwashes were provided to eighty-eight elderly participants with end-stage renal disease suffering from xerostomia. Patients were divided into 2 equal groups who used either the chamomile or placebo mouthwash for one month. The following clinical parameters (salivary flow rate, salivary ph, and salivary nitric oxide (NO) levels) were evaluated for both groups at different intervals (baseline, 1 week, and 1 month).

Detailed Description
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A double-blind (interventional) cross-sectional clinical trial was performed on 88 participants in the hemodialysis center at Benha university. The inclusion criteria were both genders above 30 years of age with ESRD and complaints of dry mouth sensation. The exclusion criteria were significant salivary gland damage (for example, due to anticancer medication), radiotherapy or chemotherapy history, and allergies). Bottles containing chamomile mouthwash or the placebo (A or B) were tagged by a reliable person outside the research group and placed inside an opaque envelope along with the questionnaires. Each patient received two envelopes containing a bottle (A & B) and a questionnaire. The results were analyzed exclusively by a statistics consultant at the end of the research. The patients were asked to express their sensation of dry mouth using subjective dry mouth score. Salivary flow rate: Eating and talking were prohibited during the time of collection. Unstimulated whole saliva was collected for 5 min by spitting method. The collection was timed, so that flow rate (mL/min) could be measured. Salivary pH: Following saliva collection, pH was measured immediately using the narrow range pH strip system (Merck). One drop of the collected saliva was placed on the test strip and its color change reflected the pH of saliva. Nitric oxide levels were determined by Nitric Oxide Assay Kit (Colorimetric) using Griess reaction: The Bio Diagnostic Nitrite Assay Kit provides an accurate and convenient method for measurement of endogenous nitrite concentration as an indicator of nitric oxide production in biological fluids. It depends on the addition of Griess Reagents which convert nitrite into a deep purple azo compound, photometric measurement of the absorbance due to this azo chromophore accurately determines NO2 - concentration.

Official Title
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Chamomile Effect on Xerostomia Associated With End-stage Renal Disease in Elderly: A Randomized Clinical Trial With a Biochemical Assessment

Conditions
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Xerostomia Due to Hyposecretion of Salivary Gland

Intervention / Treatment
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* Other: Chamomile
* Other: Saline mouthwash


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Both genders, aged above 65 years. All patients must be clinically diagnosed of ESRD undergoing hemodialysis. Patients on hemodialysis ≥ 3 months (Bots et al., 2005). All patients must have complaint of xerostomia. Objective dry mouth score from (2-5). Subjective dry mouth score from (1-4). Patients must be able to make reliable decision or communications. Exclusion Criteria: - Smoking, Alcohol. Patient with history of any serious illness as malignancy, who undergo kidney transplant. Patients with any autoimmune disease. Vulnerable groups such as prisoners, mentally and physically handicapped individuals.

Ages Eligible for Study
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Minimum Age: 66 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Treatment protocol (for the intervention group): Chamomile will topically be applied to the oral mucosa as oral rinse based on the Morales-Bozo I et al., (2017) administration protocol. Based on this protocol, patients will have oral rinses 3 times per day. Patients will be instructed to perform chamomile rinses in the oral mucosa. Patients will be instructed not to swallow the chamomile oral rinse. The control group (placebo): Patients in the control arm followed the same protocol with normal saline rinses. As stated by Kim JO and Kim NC, 2014, that use of 4% hypertonic saline solution mouthwash by elderly provided better oral health by decreasing xerostomia, oral tongue plaque, halitosis, and the number of oral bacteria. So the patients in the control group will be benefited from the saline oral rinse.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Chamomile mouthwash interventional arm in elderly patients having end-stage renal disease.<br>Chamomile was topically applied to the oral mucosa as oral rinse. Based on this protocol, patients were had oral rinses 3 times per day. Patients were instructed to perform chamomile rinses in the oral mucosa. Patients were instructed not to swallow the chamomile oral rinse. | Other: Chamomile<br>* Chamomile was topically applied to the oral mucosa as oral rinse. Based on this protocol, patients had oral rinses 3 times per day. Patients were instructed to perform chamomile rinses in the oral mucosa. Patients were instructed not to swallow the chamomile oral rinse.<br>|
| Placebo Comparator: Saline mouthwash control group in elderly patients having end-stage renal disease.<br>Patients in the control arm followed the same protocol with normal saline rinses. As stated before, that use of 4% hypertonic saline solution mouthwash by elderly provided better oral health by decreasing xerostomia, oral tongue plaque, halitosis, and the number of oral bacteria. So the patients in the control group were benefited from the saline oral rinse. | Other: Saline mouthwash<br>* Saline mouthwash was used by elderly patients in the control arm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in subjective dry mouth score | Changes in subjective dry mouth score [ Time Frame: baseline, 2 weeks and 4 weeks after intervention] The outcome measure (subjective dry mouth score) will be measured before and 2 and 4 weeks after continuous usage of chamomile mouth rinse (for at least 5 days per week) the maximum score is the worst and the minimum score is the best. | one month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Increase in unstimulated Salivary Flow Rate (ml/min) | Unstimulated whole saliva was collected for 5 min by spitting method. The collection was timed, so that flow rate (mL/min) could be measured. The normal unstimulated salivary flow rate is approximately 0.3-0.4 mL/min. A diagnosis of hyposalivation is made when the unstimulated salivary flow rate is ≤0.1 mL/min. Time Frame: baseline, 2 weeks and 4 weeks after intervention ] The outcome measure will be measured before and 2 and 4 weeks after continuous usage of chamomile mouth rinse (for at least 5 days per week) | one month | 
| Increase in salivary Nitric oxide levels (mmol/L) using clorimetric determination method | Increase in salivary Nitric oxide levels (mmol/L) using clorimetric determination method [ Time Frame: baseline and 4 weeks after intervention] The outcome measure will be measured before and 4 weeks after continuous usage of chamomile mouth rinse (for at least 5 days per week). | one month | 
| Changes in objective dry mouth score | Changes in objective dry mouth score [ Time Frame: baseline, 2 weeks and 4 weeks after intervention] The outcome measure will be measured before and 2 and 4 weeks after continuous usage of chamomile mouth rinse (for at least 5 days per week) The maximum score is the worst and the minimum score is the best. | one month | 
| Changes in salivary Potential of Hydrogen ion (pH) | Changes in salivary Potential of Hydrogen ion (pH) [ Time Frame: baseline, 2 weeks and 4 weeks after intervention ] The outcome measure will be measured before and 2 and 4 weeks after continuous usage of chamomile mouth rinse (for at least 5 days per week) | one month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chamomile, Nitric oxide, hemodialysis, xerostomia, salivary flow rate