Olfactory Disorder Clinical Trial
Official title:
Intranasal Retinoic Acid Treatment for Patients With Olfactory Loss: A Randomized Controlled Trial
About One to 2 percent of the North American population below the age of 65 years experience
olfactory loss to a significant degree. It can result from advanced age,
Post-infestious/inflammatory disorders, Obstructive disorders (e.g. nasal polyposis, tumors),
posttraumatic (head trauma) and neurodegenerative disorders. Only a few studies have shown
benefits of specific therapy for olfactory loss.
Vitamin has shown promise from both animal and human studies. However, none has studied the
benefits of topical application of vitamin A. This study will be the first to examine this
effect.
1. Purpose
To determine if there is an improvement in olfactory function following the use of
intranasal Vitamin A in patients with post-inflammatory and/or post-traumatic olfactory
loss.
2. Hypothesis
There a significant improvement in olfactory function in patients with olfactory loss
using intranasal vitamin A when compared with patients with olfactory loss not using
intranasal vitamin A
Null Hypothesis There is no significant improvement in olfactory function in patients
with olfactory loss using intranasal vitamin A when compared with patients with
olfactory loss not using intranasal vitamin A
3. Justification
To treat post inflammatory and post-traumatic olfactory loss, a few controlled studies
have shown a positive effect of a specific therapy for olfactory loss, such as olfactory
training (using repeated intensive stimulation of the olfactory system and the use of
prednisone. Other drugs studied like Vitamin B and Zinc, have either been insufficiently
studied or showed no significant effect on olfactory loss.
The use of Retinoic acid (Vitamin A), a fat-soluble vitamin, in the treatment of
olfactory loss has been previously studied in both animal and human models and showed
promise. However, no study has examined the use of topical administration of vitamin A.
This study will be the first to examine this effect.
4. Objectives
Primary Objective To determine if there is an improvement in olfactory function
following the use of intranasal Vitamin A in patients with post-inflammatory and/or
post-traumatic olfactory loss.
Secondary Objectives To determine if patient quality of life is improved/affected by the
use of intranasal vitamin A.
5. Research Method This is a Single blind Randomized Control Trial.
Procedure
The study population will be consecutive patients diagnosed with loss of olfactory
function. It will be a single blind randomized control trial. Allocation concealment
will be ensured by the use of sequentially numbered, opaque, sealed envelopes. An
assessor blinded to which patient is using vitamin A will assess the primary outcome.
Consent will be obtained for this study following diagnosis of the patient. After
diagnosis, the patient will be sent a consent form and will be recruited on the next
clinic visit.
Screening: After diagnosis, there will be a screening period; inclusion/exclusion
criteria for the study participation will be checked. Subjects who satisfy these
criteria will be invited to participate in the study. The consent forms will be sent to
them via email and their consent will be recorded.
Blinding: The study will be single-blinded study. The patients will be randomized into 3
arms/groups. An assessor blinded to which patient is using vitamin A will assess the
primary outcome.
Study Arms/Groups: The patients will be randomized into 3 groups using the sealed
envelope method. Each patient will be his or her own control. There will be two possible
scenarios resulting from randomization:
- Group A: This study group will receive intranasal vitamin A at 10,000 I.U. per day
and olfactory retraining using scented oils. Olfactory retraining is a validated
and effective method of improving olfaction in patients with olfactory loss and is
currently being used at our centre as standard of care. It involves smelling 4
scented oils for 40 minutes everyday for the duration of the study. This is
performed by the patients. They will also receive their standard of care budesonide
(Pulmicort) for their sinonasal disease. The Vitamin A will be mixed with the
budesonide and applied using the mucosal atomization device (MAD). This is a device
used to apply intranasal medication. It reduces the medication to tiny droplets so
they can reach all parts of the nose and sinuses.
- Group B: This study group will receive Vitamin A and budesonide only. They will not
receive olfactory retraining. These will also be applied using the MAD
- Group C: This study group will receive only standard of care budesonide. The
medication will also be applied using the MAD.
Patients will also continue to receive all other standard of care medication and
procedures as necessary.
6. Statistical Analysis
Sample size calculations According to the study conducted by Hummel et al, a the mean
olfactory test (TDI) score was 19 with a standard deviation of 6.4. In order to have an 80%
chance of detecting a clinically significant 6 point improvement in olfactory test (TDI)
scores at a significant level of 5%, 108 patients will be required. This will be 36 patients
per group. There is an approximately 10% drop out rate in studies conducted at the St Paul's
sinus centre. Accounting for this drop out rate, a total of 120 participants (40 participants
per group) will be required to conduct the study.
Statistical Comparisons Descriptive analysis will be used to describe demographic and some
clinical outcomes. Mean, median and standard deviations will be used to describe these
outcomes. The primary objective of this study is to compare olfactory function before and
after the respective interventions among participants in the three groups. The dichotomous
and continuous outcomes will be analyzed using Pearson Chi-squared test and analysis of
variance (ANOVA). Analysis of variance will also be used to compare the olfactory test scores
between the 3 groups and paired t-test for evaluating for statistical within the groups.
Probability values less than 5% (α=0.05) will be considered significant. Sub-analysis by
etiology of olfactory loss will also be done using the same methods.
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