Efficacy and Safety of Phototherapy in the Treatment of Loss of Smell Post Acute Infection of Coronavirus 19

Study Overview
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Brief Summary
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The aim of this study is to assess whether the use of a therapy combining olfactory training, corticoids, and phototherapy improves the PROMS compared to the use of olfactory training and corticosteroids only. To accomplish this goal the study will consist of 40 participants. The participants must present olfactory dysfunction for at least 4 weeks after a coronavirus-19 infection. Furthermore, to be eligible each participant will need a polymerase chain reaction test with positive results for coronavirus-19.

Detailed Description
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Standard Operating Procedures: Patients attending consult and calls for follow-up. Plan for missing data: Missing data will be managed with statistical tests. Statistical analysis: Categorical variables, whenever dichotomous or nominal, will be reported as frequencies and percentages. Normality will be assessed by the Kolmogorov Smirnov test. Descriptive statistics will be reported as mean (standard deviation) or median (interquartile range). To analyze the correlation between quantitative variables, the parametric Pearson test or the nonparametric Spearman's test will be used, subjected to their distribution. Differences between Diffusing capacity for carbon monoxide groups will be analyzed for statistical significance by the chi-square test for categorical variables and by a two-sample t-test or Wilcoxon rank-sum test for continuous variables as applicable. Statistical significance will be set at a P-value less than 0.05. Analyses will be performed using Statistical Package for the Social Sciences (V. 22.0) software.

Official Title
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Efficacy and Safety of Phototherapy in the Treatment of Loss of Smell Post Acute Infection of Coronavirus 19

Conditions
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Smell Disorders

Intervention / Treatment
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* Combination Product: Phototherapy
* Combination Product: OT+Corticosteroids


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Positive coronavirus polymerase chain reaction patients who experience loss of smell for more than 4 weeks after symptoms begin will be included in the study but at time of the trial with a negative result from a polymerase chain reaction. Patients older than18 years. Exclusion Criteria: Patients younger than 18 years. Pregnancy. Patients who do not have a positive real-time polymerase chain reaction for Coronavirus Patients who have contraindications for corticosteroid therapy such as: Pregnant patients Immunosuppressed Patients with peptic ulcer Diabetics Patients with glaucoma

Ages Eligible for Study
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Minimum Age: 18 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: Factorial Assignment
Interventional Model Description: Interventional study, single blinded, convenience sampling.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention group with phototherapy<br>Patients that present loss of smell 4 weeks after their coronavirus-19 infection and that have had a real-time polymerase chain reaction (reverse transcriptase polymerase chain reaction ) positive for coronavirus-19 will receive the phototherapy intervention. It consists of the introduction of the nasal probe of the phototherapy device in the nasal cavity of the patient. A mixture of ultraviolet light A, ultraviolet light B and red light will be applied between 2 and 3 minutes. The patient will receive a maximum of 10 interventions. Furthermore both oral corticosteroids (prednisone 40mg) and olfactory training will be applied, in the intervals of daily for 10 days and daily for the duration of the study respectively. | Combination Product: Phototherapy<br>* Prior to the beginning of the procedure the patient will be administered a nasal decongestant. Second to this, the patient will be advised to blow his/her nose. This step allows the physician a better view and allows the light exposure to reach the majority of the nasal mucosa(9). To start the intervention the physician will introduce the phototherapy device inside the patient's nasal cavity as the patient sits in an upright condition. As the procedure is ongoing the physician will slightly rotate the device in order to minimize dryness and to irradiate all the nasal cavity. After the intervention the patient will be administered an emollient/moisturizing drug to further hydrate the nasal mucosa(9). The intervention will have a crescent duration, the first one will be only two minutes and the following ones will increase 15 seconds each until a plateau is reached at 3 minutes in the 5th intervention.<br>* Other names: Olfactory training;|
| Active Comparator: Intervention group (corticosteroids + OT) without Phototherapy<br>Patients that present loss of smell 4 weeks after their coronavirus-19 infection and that have had a real-time polymerase chain reaction (reverse transcriptase polymerase chain reaction )and both oral corticosteroids (prednisone 40mg) and olfactory training will be applied, in the intervals of daily for 10 days and daily for the duration of the study respectively. | Combination Product: OT+Corticosteroids<br>* Patients that present loss of smell 4 weeks after their coronavirus-19 infection and that have had a real-time polymerase chain reaction (reverse transcriptase polymerase chain reaction )and both oral corticosteroids (prednisone 40mg) and olfactory training will be applied, in the intervals of daily for 10 days and daily for the duration of the study respectively.<br>* Other names: Olfactory training;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Loss of Smell in Visual Analog Scale (VAS) | The Visual Analog Scale (VAS) scale is able to determine the grade of loss of smell. From 1 to 10, being 1 the minimum and 10 the maximum grade of loss of smell. | It will be assessed through the study completion, an average of 15 weeks. | 
| Changes in the Threshold Discrimination Identification (TDI) score | The Threshold Discrimination Identification score (TDI) is used when the patient undergoes olfactory training, it is comprised by 3 tests: the threshold, discrimination, and identification. Each result is interpreted according to 4 age groups. The test is accomplished by having the patient sniff at a felt pen which has been impregnated with 4ml of odorant fluid dissolved in propylene glycol. TDI scores defined functional anosmia as a TDI score <16,5, normosmia as a TDI score >30.5 and hyposmia as a score between these two values. | It will be assessed through the study completion, an average of 15 weeks. | 
| Changes of olfactory dysfunction in the Self-reported mini olfactory questionnaire (Self-MOQ) | The Self-reported mini olfactory questionnaire (Self-MOQ) is a simple, reliable and valid questionnaire to screen olfactory dysfunction in clinical practice. For the sample in the current study, the optimal scores will be 3.5, 4.5, and 3.5 for distinguishing normosmic from hyposmic/ anosmic patients, anosmic patients, and hyposmic patients, respectively. | It will be assessed through the study completion, an average of 15 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Anxiety and depression in the Hospital Anxiety and Depression Scale(HADS) | The Hospital Anxiety and Depression Scale (HADS) allows for the assessment of both anxiety and depression as it has been seen that both can be present at the same time. This scale focuses on non-physical symptoms so that it can be used to diagnose depression in people with significant physical illness. The questionnaire comprises seven questions for both anxiety and depression, and should take around 2-5min to complete. A score between 8 and 10 is considered as mild, if it is between 11 and 14 it is considered moderate and if it exceeds 15 it is considered severe. | It will be assessed through the study completion, an average of 15 weeks. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anosmia, Hyposmia, Coronavirus, Smell Disorders, Phototherapy