Traumatic AnosmiaPhase 4theophyllineNCT07171021
The Effect of Oral Theophylline on Traumatic Anosmia
A Phase 4 study testing Theophylline 200 mg and olfactory training in people with Traumatic Anosmia, run by Taichung Veterans General Hospital at 1 site in Taiwan.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Traumatic Anosmia
- What is being tested?
- Theophylline 200 mg and olfactory training
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 158 participants
- Where
- 1 siteTaiwan
- Study dates
- 1 Dec 2020to 30 Jun 2024
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- subjects who complained of a complete loss of their smell function (anosmia) after an episode of head injury.
Who cannot join
- 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 locations and contacts
1 site in 1 country.
About this study
Official title: The Effect of Oral Theophylline on Traumatic Anosmia: A Prospective, Randomized Clinical Trial
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.
Read the 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
- Being tested
- Theophylline 200 mg, olfactory training
- Keywords
- olfactory training, smell identification, smell threshold, theophylline, traumatic anosmia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Theophylline 200 mgDrug
taking theophylline (400 mg twice a day) and performing olfactory training for 6 months
olfactory trainingBehavioural
performing olfactory training for 6 months
| Study group | Role | What they receive |
|---|---|---|
| theophylline arm | Experimental | theophylline (400 mg twice a day) and olfactory training for 6 months Receives: Drug: Theophylline 200 mg; Behavioral: olfactory training |
| control arm | Active comparator | olfactory training for 6 months Receives: Behavioral: olfactory training |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: From enrollment to the end of the treatment at 7 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2025
- Study start1 Dec 2020
- Primary completion31 Dec 2023
- Study completion30 Jun 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Traumatic AnosmiaStudies of the same condition, open and under way.
- More trials run by Taichung Veterans General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 158 participants (actual)
Sponsor and investigators
- Lead sponsor
- Taichung Veterans General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Rong-San Jiang, Taichung Veterans General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07171021
- Sponsor's protocol ID
- CF20317A
- Other IDs
- TCVGH-1117310C
- Acronym
- theophylline
- Status last verified
- Sep 2025
- First submitted
- 5 Sep 2025
- Last updated
- 12 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: all IPD that underlie results in a publication
Publications
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.
PubMed 19359985
Study at a glance
From the registry record, last updated by the sponsor on 12 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Oral Theophylline on Traumatic Anosmia: A Prospective, Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT07171021
- Acronym / sponsor ID
- theophylline / CF20317A
- Conditions
- Traumatic Anosmia
- Keywords
- olfactory training, smell identification, smell threshold, theophylline, traumatic anosmia
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 158 participants (actual)
- Lead sponsor
- Taichung Veterans General HospitalUniversity, hospital or other
- Study start
- 1 Dec 2020 (actual)
- Primary completion
- 31 Dec 2023 (actual)
- Study completion
- 30 Jun 2024 (actual)
- First posted
- 12 Sep 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| theophylline arm | Experimental | Drug: Theophylline 200 mg, Behavioral: olfactory trainingtheophylline (400 mg twice a day) and olfactory training for 6 months |
| control arm | Active comparator | Behavioral: olfactory trainingolfactory training for 6 months |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- subjects who complained of a complete loss of their smell function (anosmia) after an episode of head injury.
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Theophylline 200 mgtaking theophylline (400 mg twice a day) and performing olfactory training for 6 months | Drug | theophylline arm |
| olfactory trainingperforming olfactory training for 6 months | Behavioural | control arm, theophylline arm |
Primary outcome
Change of olfactory identification ability of participants with treatment as assessed by Traditional Chinese Version of the University of Pennsylvania Identification Test
Time frame: From 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 test
Time frame: From 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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Sep 2025.
- Background: PubMed 19359985Henkin 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.
- Individual participant dataSharing planned: Yes. all IPD that underlie results in a publication
Related trials for Traumatic Anosmia
Not yet recruiting
PANDORA: Evaluation of Platelet-rich Plasma in Non-tumoural Odour Disorders: a Descriptive Pilot Study.
Olfactory Dysfunction, Post-traumatic Olfactory Dysfunction
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Theophylline 200 mg and olfactory training in people with Traumatic Anosmia, run by Taichung Veterans General Hospital at 1 site in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change of olfactory identification ability of participants with treatment as assessed by Traditional Chinese Version of the University of Pennsylvania Identification Test (time frame: From enrollment to the end of treatment at 7 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07171021, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Sep 2025.