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The Effect of Oral Theophylline on Traumatic Anosmia (theophylline)

T

Taichung Veterans General Hospital

Status and phase

Completed
Phase 4

Conditions

Traumatic Anosmia

Treatments

Drug: Theophylline 200 mg
Behavioral: olfactory training

Study type

Interventional

Funder types

Other

Identifiers

NCT07171021
CF20317A
TCVGH-1117310C (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment

158 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Double Blind

158 participants in 2 patient groups

theophylline arm
Experimental group
Description:
theophylline (400 mg twice a day) and olfactory training for 6 months
Treatment:
Behavioral: olfactory training
Drug: Theophylline 200 mg
control arm
Active Comparator group
Description:
olfactory training for 6 months
Treatment:
Behavioral: olfactory training

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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