Testing gabapentin to treat distorted senses of smell after a viral infection
| ISRCTN | ISRCTN82171427 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN82171427 |
| IRAS number | 1012783 |
| Secondary identifying numbers | 164150 |
- Submission date
- 16/09/2025
- Registration date
- 10/11/2025
- Last edited
- 10/11/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Ear, Nose and Throat
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year
Plain English summary of protocol
Background and study aims
Parosmia is a condition where the sense of smell becomes distorted. People with parosmia often report that normal smells, such as coffee or food, are unpleasant or foul. This condition is commonly seen after viral infections, especially COVID-19. It can have a serious impact on daily life.
At the moment, there are no proven treatments. This study will investigate whether a medicine called gabapentin can help reduce the symptoms of parosmia. Gabapentin is already used to treat nerve pain and epilepsy. It works by calming overactive nerves and may help reduce the abnormal smell signals that cause parosmia.
The main question the research aims to answer is whether gabapentin is a safe and effective treatment for people with parosmia after a viral infection. If successful, this treatment could offer new hope to many people affected by this condition.
Who can participate?
To take part, people must be aged 18 to 65 and have had parosmia for more than 3 months but less than 3 years after a viral illness.
What does the study involve?
The study is a clinical trial. People who take part will be randomly placed into one of two groups. One group will receive gabapentin and the other will receive a placebo. A placebo is a capsule that looks like the real medicine but does not contain any active ingredients. The study is double blind which means that neither the participants nor the researchers will know who is receiving which treatment during the study. Participants will complete a smell questionnaire called Smell Qx at the start of the study, after 8 weeks of treatment and again at 12 weeks. Each person will be involved in the study for 12 weeks in total.
What are the possible benefits and risks of participating?
Not provided at time of registration
Where is the study run from?
The study will take place at Homerton Healthcare NHS Foundation Trust and James Paget University Hospitals NHS Foundation Trust.
When is the study starting and how long is it expected to run for?
September 2025 to February 2027
Who is funding the study?
Rosetrees Trust (UK)
Who is the main contact?
Andrew Tunstell, a.tunstell@ucl.ac.uk
Contact information
Mr Andrew Tunstell
Public
Public
University College London
London
NW1 2PG
United Kingdom
| Phone | +44 20 3447 5369 |
|---|---|
| a.tunstell@ucl.ac.uk |
Prof Matt Lechner
Principal investigator
Principal investigator
University College London Division of Surgery and Interventional Science, Charles Bell House, 43-35 Foley Street
London
W1W 7TS
United Kingdom
| Phone | +44 7535660441 |
|---|---|
| m.lechner@ucl.ac.uk |
Dr Umar Rehman
Scientific
Scientific
University College London Division of Surgery and Interventional Science, Charles Bell House, 43-35 Foley Street
London
W1W 7TS
United Kingdom
| Phone | +44 7415345603 |
|---|---|
| U.rehman@ucl.ac.uk |
Study information
| Study design | Interventional double blind randomized parallel group placebo controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Efficacy, Safety |
| Scientific title | Use of gabapentin in the management of post-viral parosmia: a double-blind, randomised, placebo-controlled, multi-site trial |
| Study acronym | COPANOS |
| Study objectives | Primary objective: To assess the efficacy of gabapentin treatment in the management of parosmia. The primary outcome measure will be the difference in the participant reported parosmia symptom severity assessed via the parosmia domain of the Smell Qx survey scores between gabapentin and placebo treated groups following completion of treatment. (Week 8). The study also aims to find out: 1. Whether gabapentin is safe and well tolerated by people taking it. 2. If gabapentin improves quality of life in people with parosmia. 3. Whether gabapentin improves the sense of smell, based on smell tests. 4. If it reduces the severity of parosmia, as measured by both patient reports and objective parosmia tests. |
| Ethics approval(s) |
Not yet submitted, ref: 25/WA/0298 |
| Health condition(s) or problem(s) studied | Post-viral Parosmia (distorted smell) |
| Intervention | This is a double-blind, randomised, placebo-controlled trial investigating the efficacy of gabapentin in the treatment of parosmia. Participants will be randomised in a 1:1 ratio to receive either gabapentin or placebo. Randomisation will be conducted using a computer-generated sequence via Sealed Envelope, employing permuted-block sequencing. Randomisation will be stratified by baseline parosmia severity (Smell Qx parosmia domain), duration of parosmia, age, gender, and Sniffin’ Sticks Threshold-Discrimination-Identification (TDI) scores to ensure balance across trial arms. Active Intervention (Gabapentin): Participants randomised to the active treatment arm will receive gabapentin capsules (300 mg per capsule) administered orally for a total treatment duration of 8 weeks, followed by a weaning phase. The dosing regimen is as follows: Weeks 1–2: one capsule (300 mg) once daily in the evening; Weeks 3–6: one capsule (300 mg) twice daily, every 12 hours (total daily dose 600 mg); Weeks 7–8 (weaning phase): one capsule (300 mg) once daily in the evening. In total, each participant will receive 84 capsules over the treatment course. Dose adjustments are permitted for tolerability: participants experiencing non-serious side effects such as intolerable daytime drowsiness may reduce to 300 mg once daily; additionally, participants reporting subjective symptomatic improvement by Week 2 (based on the Smell Qx parosmia domain) may elect to remain on 300 mg daily rather than escalating to 600 mg daily. Participants will be supplied with medication in two batches: the first at baseline (Visit 1) and the second at Week 3. Comparator (Placebo): Participants randomised to placebo will receive identically packaged and over-encapsulated placebo capsules, manufactured by Zentiva, matched in appearance, quantity, and dosing schedule to the gabapentin arm. Participants in this arm will follow the same dose-escalation and weaning schedule (Weeks 1–2: one capsule daily; Weeks 3–6: one capsule twice daily; Weeks 7–8: one capsule daily), with the same opportunity for individualised adjustment based on tolerability or subjective improvement, to preserve blinding and procedural equivalence with the active arm. Follow-Up and Monitoring: Following randomisation, participants will attend clinic visits at baseline (Visit 1), end of treatment (Week 8, Visit 2), and final follow-up (Week 12, Visit 3). Virtual or telephone follow-ups will occur weekly during Weeks 2–6 to monitor treatment compliance, adverse events, and suicidal ideation using the Columbia-Suicide Severity Rating Scale (C-SSRS). At Week 3, participants will attend the pharmacy to collect the remaining study medication, with no additional trial assessments performed at this visit. Adverse event monitoring will occur throughout, including review of patient diaries and pill counts. Safety provisions are in place to discontinue medication in cases of intermediate or high suicide risk, allergic reaction, or intolerable side effects. This design ensures robust evaluation of gabapentin versus placebo, with identical treatment schedules, dose escalation and weaning phases, compliance monitoring, and blinded assessment of outcomes. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Dose response, Therapy |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | Gabapentin |
| Primary outcome measure | Parosmia severity is measured using the Parosmia Domain of the Smell Qx questionnaire (scale 1–5, higher scores = worse severity) at baseline (Week 0), end of treatment (Week 8), and 1-month post-treatment follow-up (Week 12). |
| Secondary outcome measures | 1. Parosmia severity is measured using the Parosmia Domain (scale 1–5, higher scores = worse severity) of the Smell Qx questionnaire at baseline (Week 0), end of treatment (Week 8), and follow-up (Week 12). 2. Safety and tolerability are measured by the number and proportion of participants reporting adverse drug reactions, and by responses on the Columbia-Suicide Severity Rating Scale (C-SSRS), at baseline (Week 0), weekly telephone follow-ups during treatment (Weeks 2–6), end of treatment (Week 8), and follow-up (Week 12). 3. Quality of life is measured using the Quality-of-Life Domain of the Smell Qx questionnaire (scale 1–5) at baseline (Week 0), end of treatment (Week 8), and follow-up (Week 12). 4. Olfactory function is measured using the Sniffin’ Sticks Threshold-Discrimination-Identification (TDI) test (total score 0–48; <16.5 anosmia, 16.5–30.5 hyposmia, >30.5 normosmia) at baseline (Week 0), end of treatment (Week 8), and follow-up (Week 12). 5. Objective parosmia severity is measured using the Sniffin’ Sticks Parosmia Test (SSParoT; Hedonic Range and Hedonic Direction scores) at baseline (Week 0), end of treatment (Week 8), and follow-up (Week 12). Exploratory Outcomes 1. Cognitive function is measured using the Addenbrooke’s Cognitive Examination III (ACE-III; total score 0–100, <77 indicates impairment) at baseline (Week 0) and end of treatment (Week 8). 2. Nasal airflow is measured using peak nasal inspiratory flow, nasal partitioning ratio, tidal volume, double ordinal airway subjective scale, and maximal inhalation flow rate at baseline (Week 0) and end of treatment (Week 8). 3. Taste function is measured using Taste Strips (maximum score 16; <9 hypogeusia, misidentification at highest concentrations = dysgeusia) at baseline (Week 0), end of treatment (Week 8), and follow-up (Week 12). 4. Trigeminal sensitivity is measured by the number of correct lateralisation responses to 40 odour stimuli (benzaldehyde and eucalyptol vs propylene glycol) at baseline (Week 0) and end of treatment (Week 8). 5. Effect of gabapentin dose is measured by comparing Smell Qx Parosmia Domain scores between participants taking 300mg vs 600mg daily at the end of treatment (Week 8) |
| Overall study start date | 11/09/2025 |
| Completion date | 01/02/2027 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 65 Years |
| Sex | All |
| Target number of participants | 90 |
| Key inclusion criteria | 1. Participants aged 18–65 years with parosmia secondary to viral infection/COVID-19 infection (≥6 months duration but less than 5 years) 2. Participants must have a Parosmia domain severity score of ≥3/5 on the Smell Qx 3. Participants must have a sniffin stick smell TDI >16.5 4. Participants must be willing able to provide written informed consent 5. Fluent in English and able to understand and complete questionnaires 6. Women of childbearing potential must be willing to use a highly effective method of contraception from consent until end of the trial 7. Female participants of childbearing potential must have a negative urine pregnancy test which will be done at the baseline visit before randomisation and start of trial treatment |
| Key exclusion criteria | 1. Participants with known allergies to the odours used in Sniffin Sticks TDI assessment, retronasal olfactory tests or taste strips. 2. Participants with a known allergy to the IMP or its excipients. 3. Parosmia which is primarily associated with chronic sinusitis with or without nasal polyps, allergic rhinitis, sinonasal tumours or other aetiologies. 4. Participants using concurrent medication as listed in Section 8.7. Participants with use of antidepressants/antipsychotics/GABA analogues in the last 12 months. 5. Participants with a history of depression, anxiety, psychosis, self-harm, suicide attempts, or other mental health conditions. 6. Participants who have experienced suicidal or self-harm thoughts within the past month. Participants with any history of neurological conditions e.g. Alzheimer's, Dementia, Parkinsons, Epilepsy, Traumatic Brain Injury or Brain Tumours. 7. Participants with any history of renal failure, dialysis patient, previous renal transplant or known creatinine clearance <30ml/min.* 8. Participants with any history of liver failure, liver disease or previous liver transplant. 9. Participants with a family history of chronic kidney disease, or those currently taking or who have taken a prolonged course (2 weeks or greater) of medications known to affect renal function within the past 6 months, will undergo renal function testing (e.g., creatinine clearance). Medications known to impact renal function include but are not limited too: diuretics such as furosemide, aminoglycosides such as gentamicin, antihypertensives such as ramipril, nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, as well as certain antivirals, chemotherapy agents, and calcineurin inhibitors. Individuals with a creatinine clearance of less than 30 mL/min will be excluded from the study. Participants who have comorbidities known to impact renal function such as diabetes, hypertension, cardiovascular disease including previous myocardial infarction, and autoimmune conditions such as systemic lupus erythematosus or rheumatoid arthritis will undergo renal function blood testing. Individuals with a creatinine clearance of less than 30 mL/min will be excluded from the study. 10. Participants with any history of cardiac arrythmias or diagnosed heart failure. 11. Females who are currently pregnant, planning pregnancy or breastfeeding. 12. Participants with a current or any previous addiction to alcohol, cocaine, opiates or any other recreational or prescription medications. 13. Participants operating heavy machinery, working at heights or operating buses/trains/plane/driving long distances. 14. Participants currently involved in, or who have participated within the past 12 months in, any research study involving experimental medications or drug trials. 15. Participants with a diagnosis of cancer who are undergoing active treatment. 16. Participants who are using over-the-counter treatments for olfactory dysfunction, such as vitamin A or omega-3 fatty acids. Participants who are immunocompromised, including those with HIV infection, active malignancy, or currently receiving chemotherapy, immunosuppressive therapy, or long-term corticosteroids, will be excluded from the study. 17. Participants with significant respiratory conditions, such as chronic obstructive pulmonary disease (COPD), severe asthma, or other uncontrolled respiratory diseases, who have required hospitalisation in the past 12 months, require long term oxygen therapy, non-invasive ventilation, long term oral corticosteroids, at home nebulisers or requiring lung surgery will be excluded from the study. 18. Participants with resistant hypertension, defined as uncontrolled hypertension despite requiring an ACE inhibitor or an ARB plus a CCB and a thiazide-like diuretic or under the care of a specialist hypertension clinic, will be excluded. 19. Participants with a history of blood or clotting disorders (e.g. thrombocytopenia, leukaemia) or those taking antiplatelet agents (e.g. aspirin, clopidogrel) will be excluded. * Creatinine clearance will not be routinely assessed as gabapentin is not reported to be nephrotoxic. It will be evaluated in individuals with: • Known renal disorders (e.g. glomerulonephritis, nephrotic syndrome) • Systemic conditions that may affect renal function (e.g. diabetes mellitus, systemic lupus erythematosus, hypertension) • Use of nephrotoxic medications (e.g. aminoglycosides, Non-steroidal anti-inflammatory drugs (NSAIDs), antihypertensive medications) |
| Date of first enrolment | 13/10/2025 |
| Date of final enrolment | 01/03/2027 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Homerton Healthcare NHS Foundation Trust
Homerton Row
London
E9 6SR
United Kingdom
London
E9 6SR
United Kingdom
James Paget University Hospitals NHS Foundation Trust
Lowestoft Road
Gorleston
Great Yarmouth
NR31 6LA
United Kingdom
Gorleston
Great Yarmouth
NR31 6LA
United Kingdom
Sponsor information
University College London
University/education
University/education
Charles Bell House, 43-45 Foley Street
London
W1W 7TS
England
United Kingdom
| Phone | +44 7415345603 |
|---|---|
| u.rehman@ucl.ac.uk | |
| Website | http://www.ucl.ac.uk/ |
"ROR" |
https://ror.org/02jx3x895 |
Funders
Funder type
Charity
Rosetrees Trust
Private sector organisation / Trusts, charities, foundations (both public and private)
Private sector organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- Teresa Rosenbaum Golden Charitable Trust, Rosetrees
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 01/02/2028 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Submission to regulatory authorities Other All data generated during this trial will be the property of University College London (UCL), the study Sponsor. Following completion of the trial, data will be analysed and a final trial report prepared. Results will be published in a peer-reviewed journal, with the study protocol also made publicly available. The Rosetrees Trust, which is funding the study, will be acknowledged in all publications. Participants will be informed of the trial results, with a summary available upon request and a link to the published manuscript provided. Authorship of resulting publications will follow International Committee of Medical Journal Editors (ICMJE) guidelines and will be limited to those who have made substantial contributions to the study. No professional writers will be used, and publication by participating investigators will require approval by the Chief Investigator and Sponsor. To promote transparency, maximise the value of the data, and contribute to future scientific research, anonymised data from this trial may be shared with other researchers. This may include use in secondary analyses or meta-analyses. All shared data will be fully anonymised so that individuals cannot be identified. Identifiable information will not be shared outside the research team. The Participant Information Sheet explains the possibility of data being used for future research and makes clear that consent will be sought for this. Providing this consent is entirely voluntary. Participants can choose whether or not to allow their data to be used in future research, and this decision will not affect their ability to take part in the main trial. All future use of data will comply with UK GDPR and the Data Protection Act 2018. |
| IPD sharing plan | The current data sharing plans for this study are unknown and will be available at a later date |
Editorial Notes
16/09/2025: Trial's existence confirmed by NHS HRA.
