Post-viral Parosmia (distorted smell) Ear, Nose and Throat
Conditions
Interventions
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 gab
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 tolerabilit
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. Pa
Sponsors
University College London
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Inclusion criteria
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
Exclusion criteria
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 thera
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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; 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 (W | — |
Countries
England, United Kingdom
Contacts
Public ContactAndrew Tunstell
Outcome results
None listed