The Effect of Oral Theophylline on Traumatic Anosmia

NCT ID: NCT07171021

Last Updated: 2025-09-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 158 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-01
• Study Completion Date: 2024-06-30

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.

Conditions

Traumatic Anosmia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

theophylline arm

theophylline (400 mg twice a day) and olfactory training for 6 months

Group Type: EXPERIMENTAL

Theophylline 200 mg

Intervention Type: DRUG

taking theophylline (400 mg twice a day) and performing olfactory training for 6 months

olfactory training

Intervention Type: BEHAVIORAL

performing olfactory training for 6 months

control arm

olfactory training for 6 months

Group Type: ACTIVE_COMPARATOR

olfactory training

Intervention Type: BEHAVIORAL

performing olfactory training for 6 months

Interventions

Theophylline 200 mg

taking theophylline (400 mg twice a day) and performing olfactory training for 6 months

Intervention Type: DRUG

olfactory training

performing olfactory training for 6 months

Intervention Type: BEHAVIORAL

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Taichung Veterans General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Rong-San Jiang

Visiting Doctor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Taichung Veterans General Hospital

Taichung, , Taiwan

Countries

Taiwan

References

Henkin RI, Velicu I, Schmidt L. An open-label controlled trial of theophylline for treatment of patients with hyposmia. Am J Med Sci. 2009 Jun;337(6):396-406. doi: 10.1097/MAJ.0b013e3181914a97.

Reference Type: BACKGROUND

PMID: 19359985 (View on PubMed)

Other Identifiers

TCVGH-1117310C

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

CF20317A

Identifier Type: -

Identifier Source: org_study_id