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The Effect of Oral Theophylline on Traumatic Anosmia

Not Applicable
Completed
Conditions
Traumatic Anosmia
Interventions
Behavioral: olfactory training
Registration Number
NCT07171021
Lead Sponsor
Taichung Veterans General Hospital
Brief Summary

This study aimed to improve the treatment outcomes of patients with post-traumatic anosmia through medication and olfactory training. Number of subjects and selection criteria: 160 patients were enrolled in the ENT and head and neck outpatient clinic with a history of head trauma, a complaint of anosmia, and evidence of olfactory examination. Their olfactory status had not improved after steroids, zinc tablets, and olfactory training. Exclusion criteria: Patients under 20 years of age, pregnant or breastfeeding women, and those with compromised immune systems were excluded.

Patients who did not improve after medication and olfactory training were randomized. One group received theophylline and zinc tablets with continued olfactory training, while the other group received zinc tablets alone with continued olfactory training. Patients returned for follow-up and medical consultation after treatment at the 24th week. Theophylline medication: Theophylline (200 mg, two tablets twice daily) was administered for 24 weeks.

Detailed Description

We collected subjects who complained of a complete loss of their smell function (anosmia) after an episode of head injury between December 2020 and December 2023. Any patient who had a history of loss of olfactory function before head trauma or sinus surgery was excluded from the study. If the etiology of loss of olfactory function was suspected to not be caused by head trauma, it was also excluded. The remaining patients received right and left unilateral phenyl ethyl alcohol (PEA) odor detection threshold tests to assess their olfactory function. The definition of anosmia in this study was that the unilateral PEA thresholds for the right and left were -1. Anosmic patients were included in this study. These anosmic patients were then treated with high-dose prednisolone (1 mg/kg per day for 3 days) with tapering, along with zinc gluconate (10 mg three times a day) for a period of 1 month. Classic OT using 4 separate bottles of PEA, lemon, eucalyptus, and clove oil was also started. The patients were told to sniff each odorant for 10 seconds, twice a day.21 After one month of treatment, all patients received unilateral right and left PEA odor detection threshold tests and the traditional Chinese version of the University of Pennsylvania Identification Test (UPSIT-TC) to assess their olfactory function. Those whose unilateral PEA thresholds on the right and left remained -1 were enrolled in this study.

The eligible patients were randomly divided into 2 groups. Randomized assignment to the two groups was performed by an independent statistician. The patients in the theophylline group took theophylline (400 mg twice a day) for 6 months and continued OT. Those who were assigned to the OT group continued OT for 6 months without any other form of treatment.

All patients returned to the clinic to receive another series of unilateral right and left PEA threshold tests and UPSIT-TC at the end of 6 months of treatment. Patients taking oral theophylline also received blood tests to measure blood theophylline levels. Brain magnetic resonance imaging (MRI) was performed to measure the volumes of olfactory bulbs (OB) following completion of the 6-month treatment. During the 6-month treatment period, drugs such as oral or nasal steroids, vitamin A, zinc, and antihistamines were not allowed.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
158
Inclusion Criteria
  • subjects who complained of a complete loss of their smell function (anosmia) after an episode of head injury.
Exclusion Criteria
  • patients without a complete loss of their smell function
  • a history of loss of olfactory function before head trauma or sinus surgery
  • the etiology of loss of olfactory function was suspected to not be caused by head trauma

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
theophylline armTheophylline 200 mgtheophylline (400 mg twice a day) and olfactory training for 6 months
theophylline armolfactory trainingtheophylline (400 mg twice a day) and olfactory training for 6 months
control armolfactory trainingolfactory training for 6 months
Primary Outcome Measures
NameTimeMethod
Change of olfactory identification ability of participants with treatment as assessed by Traditional Chinese Version of the University of Pennsylvania Identification TestFrom enrollment to the end of treatment at 7 months

The test consists of 40 tests as it follows the North American version of the University of Pennsylvania Smell Identification Test. In each test, the brown strip at the bottom of the test page consists of microcapsules of an odorant that are released by scratching the strip with a pencil tip. The patient sniffs the released odorant and selects a response from four odor descriptor options that are used to identify the odorant. The test score is the number of correct responses among the 40 tests taken.

Olfactory threshold change of participants with intervention drug as assessed by phenyl ethyl alcohol odor detection threshold testFrom enrollment to the end of the treatment at 7 months

The test uses different concentrations of a phenyl ethyl alcohol odorant to measure a patient's odor detection threshold. The strongest concentration is a concentration of phenyl ethyl alcohol at 10-1 log vol/vol. Then, the concentration of the odorant is diluted with mineral oil in half-log steps until the weakest concentration at 10-9 log vol/vol. A 2-alternative forced choice single-staircase procedure is used to decide the odor detection threshold. The threshold ranges from -1 to -9.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

Taichung Veterans General Hospital

🇨🇳

Taichung, Taiwan

Taichung Veterans General Hospital
🇨🇳Taichung, Taiwan

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