The Effect of Oral Theophylline on Traumatic Anosmia

NCT07171021 | Completed Phase 4 DMC

• 2 other identifiers: CF20317ATCVGH-1117310C
• Study Type: interventional
• Target: 158
• Locations: 1 country
• Sites: 1

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.

Conditions

Traumatic Anosmia

Keywords

olfactory training, smell identification, smell threshold, theophylline, traumatic anosmia

Outcome Measures

Primary Outcomes (2)

• Change of olfactory identification ability of participants with treatment as assessed by Traditional Chinese Version of the University of Pennsylvania Identification Test

  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.

  From enrollment to the end of treatment at 7 months

• Olfactory threshold change of participants with intervention drug as assessed by phenyl ethyl alcohol odor detection threshold test

  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.

  From enrollment to the end of the treatment at 7 months

Study Arms (2)

theophylline arm

EXPERIMENTAL

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

Drug: Theophylline 200 mg; Behavioral: olfactory training

control arm

ACTIVE COMPARATOR

olfactory training for 6 months

Behavioral: olfactory training

Interventions

Theophylline 200 mg DRUG

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

theophylline arm

olfactory training BEHAVIORAL

performing olfactory training for 6 months

control arm; theophylline arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• subjects who complained of a complete loss of their smell function (anosmia) after an episode of head injury.

You may not qualify if:

• 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

Sponsors & Collaborators

• Taichung Veterans General Hospital: lead

Study Sites (1)

Taichung Veterans General Hospital

Taichung, 40705, Taiwan

Location

Related Publications (1)

• 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.

  PMID: 19359985 BACKGROUND

MeSH Terms

Interventions

Theophylline; Olfactory Training

Intervention Hierarchy (Ancestors)

Xanthines; Alkaloids; Heterocyclic Compounds; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Visiting Doctor

Study Record Dates

• First Submitted: September 5, 2025
• First Posted: September 12, 2025
• Study Start: December 1, 2020
• Primary Completion: December 31, 2023
• Study Completion: June 30, 2024
• Last Updated: September 12, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: October 2025- October 2025
• Access Criteria: Request to Central contact person

Locations

TW (1)