Active Research Studies
Full Title: A 24-Week Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study Evaluating the Efficacy and Safety of Intranasal Administration
of 186 and 372 μg of OPN-375 Twice a Day (BID) in Subjects with Chronic Sinusitis Without the Presence of Nasal Polyps
IRAS Project ID: 266771
Sponsor: OptiNose US, Inc.
Chief Investigator: Prof Carl Philpott
Chief Investigator : Peter Prinsley
Research Ethics Committee : East of England - Cambridge
Research Ethics Committee number : 16/EE/0131
Funders: Rosetrees Foundation and the Royal College of Surgeons of England
Study summary : A clinical observation that a form of ear disease called cholesteatoma appears to run in families has been made in East Anglia. Cholesteatoma is chronic and potentially serious cause of deafness where there is destruction of the delicate structures of the ear and is treated by ear surgery. We are seeking to identify family pedigrees and subsequently to collect blood samples for genetic analysis. The aim of this study is to identify a genetic basis for the disease. We will identify families from clinical records and through the network of the British Society of Otology. We will approach these families to ask for their consent to provide family trees and subsequently blood samples. The latter will be used for a form of analysis known as genome sequencing which will provide information on any significant variants that are associated with the clinical trait.
Peter Prinsley (Protocol queries) - firstname.lastname@example.org
Jane Woods (Data collection queries) - email@example.com
Chief Investigator: Carl Philpott
Research Ethics Committee: East Midlands - Leicester Central Research Ethics Committee
Research Ethics Committee number: 16/EM/0468
Funder: Sir Jules Thorn Charitable Trust
Study summary :
Chronic rhinosinusitis (CRS) represents a common source of ill health, with symptoms including nasal obstruction, nasal discharge, facial pain, anosmia and sleep disturbance. CRS is divided phenotypically into those with polyps (CRSwNPs) and without polyps (CRSsNPs). CRS can also be categorised by endotypes which represent a subtype of the condition defined by a distinct functional or pathobiological mechanism. These endotypes may indicate the potential for personalised medical and surgical treatment, due to differences in responsiveness to treatments such as intranasal corticosteroids and biological agents. It is likely that these differences reflect differing pathophysiology between cases and are based on specific cytokine signatures.
The MACRO Programme, “Defining best Management in Adult Chronic RhinOsinusitis” is funded by NIHR at £3.2 million and a clinical trial workstream commenced in December 2017. The trial compares the effectiveness of both clarithromycin for 3 months and endoscopic sinus surgery. The ExpRess study (Exploring Endotypes in Chronic Rhinosinusitis) aims to collect nasal tissue samples from subjects recruited to the MACRO trial for cytokine analysis to compare responders and non-responders to interventions. This data will enable a clearer definition of potential disease endotypes and their relationship to the clinical phenotypes and subsequent treatment.
Chief Investigator: Carl Philpott
Research Ethics Committee: South Central - Oxford C Research Ethics Services
Research Ethics Committee Number: 18/SC/0593
Funder: MRes Consumables Project at Norwich Medical School
Study Summary: Olfactory dysfunction is common health condition which increases with age. Approximately 5% of the general population have no practical use of their sense of smell (functional anosmia). Olfactory dysfunction has been demonstrated to impact quality of life through loss of smell rich experiences (e.g. food, beverages, perfume) and can be life-threatening when limiting the ability to recognise danger (e.g. smoke, gas leaks, spoiled food). Tumour Necrosis Factor-alpha (TNF-a) antagonists are a group of medications which stop the effects of TNF-a, a molecule which causes inflammation. Two previous studies have shown benefit of TNF-a antagonists in mice’s sense of smell. However, little research has been done on humans. Rheumatology patients that are TNF-a antagonist naïve shall be approached and their sense of smell measured before initiation and after 3 months of treatment. The aim is to determine the affect TNF-a antagonists have on olfactory performance.
Synopsis: Chronic Rhinosinusitis (CRS) represents a common source of ill health; 11% of UK adults report CRS symptoms in a worldwide population study. Symptoms include nasal obstruction and discharge, facial pain, and sleep disturbance. It can have a major impact on quality of life, reportedly greater in several domains of the SF-36 than angina or chronic respiratory disease. Acute exacerbations, inadequate symptom control and respiratory disease exacerbation are common. Complications are rare, but may include visual impairment and intracranial infection. Data from the Clinical Practice Research Datalink (CPRD) shows that 1% of UK adults receive treatment for CRS from their GP each year, averaging 4 GP visits; they receive multiple medications with 91% receiving an antibiotic prescription. Data from Hospital Episode Statistics (HES) for 2012-13 shows that approximately 40,000 sinus operations were performed in England and Wales, in addition to an estimated 120,000 outpatient consultations. A worldwide study found that one in three CRS patients in primary care have poorly controlled symptoms. The socio-economic cost of CRS is significant with 57% of patients report absenteeism and 28% experience associated anxiety and depression. CRS has been reported as one of the top 10 illnesses causing absence from work in the US. Although long-term macrolide use and endoscopic sinus surgery appear as recommendations in international guidelines, randomised controls for the latter are lacking and the only two for macrolides had opposing outcomes. Hence there is equipoise about the role of these two interventions for CRS.
Further information on the programme can be found at the MACRO trial set up page.
Chief investigator: Professor Carl Philpott
Research Ethics Committee: West of Scotland Research Ethics Service
Research Ethics Committee Number: 18/WS/0213
Funder: MRes Consumables Project at the Norwich Medical School, University of East Anglia
Olfactory dysfunction is common following trauma and occurs in approximately 20% of traumatic brain injury cases. Approximately 1 in 2 patients with an olfactory deficit (hyposmia or anosmia) following head injury are unaware of their sensory deficit. Early recognition of olfactory impairment is important for the clinician and patient to avoid risks associated with olfactory loss (e.g. recognition of spoiled food, gas, smoke), to manage associated limitations and to receive earlier treatment (e.g. steroids, olfactory retraining). Following head injury sense of smell is often clinically unassessed. Smell tests can take a significant length of time and therefore have reduced clinical application in asymptomatic patients. This study is investigating the role of a non-invasive screening smell test (Burghart Screening 12 test) which takes a short period of time to complete, in adult patients who require secondary care assessment following a head injury.
Chief Investigator : Professor Gavin Giovannoni
Research Ethics Committee :
Research Ethics Committee number :
Funder: Parkinsons UK
Study summary : A number of risk factors have been reported before the onset of overt motor signs indicative of PD. These include anosmia, RBD, constipation, and depression. Smoking and use of caffeine, alcohol, and some NSAIDs have been suggested to reduce risk. Individually, most factors convey only a modest effect on overall risk, but may summate with considerable predictive power.
The main objective is to determine whether a combination of risk factors for Parkinson's disease (PD) can identify subjects at high risk by testing for anosmia and REM sleep behavioural disorder (RBD).
More information can be found on the Parkinson's UK website.
To find out whether there is an increase in the size and activity of damaged smell pathways in patients’ brains when they are treated with vitamin A nasal drops. This would show recovery of the damage caused by common viral infections in the nose.
Loss of smell affects an estimated 5% of people leading to depression, anxiety and isolation as well as changes in weight due to reduced appetite. Viral infections in the nose, including common colds and Covid-19, are the second most common cause of this smell loss. A recent limited study in Germany using vitamin A nasal drops showed that those in the treated group improved twice as much as those in the untreated group, lasting at least 10 months. It is thought that this treatment works to help repair tissues in the nose damaged by the viruses. This work will explore whether this is correct.
Design and methods
We will invite people who have been found to have smell loss due to a previous viral infection to join the study. They can join when they attend the Norfolk Smell & Taste Clinic, or through Fifth Sense, the smell and taste disorders charity. Those able to join will be randomly allocated to one of two groups: 38 patients will receive a 12-week course of nasal vitamin A drops and 19 will receive inactive peanut oil drops. Both sets of patients will receive brain scans, before and after the 12-week interval. We will look for changes in the size of the olfactory bulb (an area above the nose where the smell nerves join together and connect to the brain), that can be measured.
We will also look at activity in areas of the brain linked to recognising smells. The patients will be smelling odours (roses and rotten eggs) while special brain scans are taken that use a magnet to create images. A smell test and a questionnaire will also measure smell loss and its daily impact at the two visits.
Patient and public involvement
A PPI representative is part of the research team and has reviewed the application. In preparing this proposal we used feedback from 120 survey respondents with this type of smell loss and PPI input will continue throughout the study.
Using the research team’s links we will share the study results with doctors though journal publications and conferences. Through the patient charity, Fifth Sense, we will inform those who took part and the public using newsletters, social media, patient community groups and leaflets. If this study shows a positive effect, we will also propose a follow-on trial to establish the benefit of this treatment for these smell loss patients.
Past Research Projects
- Chronic Rhinosinusitis Epidemiology Study (CRES)
- Developing a Core outcome set for trials of intervention in Chronic Rhinosinusitis (Delphi)
- Eustachian Tube Dysfunction Chronic Rhinosinusitis Study
- MACRO qualitative research
- Outcome assessment of rhinosinusitis in MACRO
- Personal Accounts of Anosmia
- Sniffin' Sticks
- The Socioeconomic Impact of Chronic Rhinosinusitis Study (SoCCoR)
- Sodium Citrate Trial
- Sinus 24
- NAIROS: Nasal Airway Obstruction Study
- Covid-19 and Anosmia Study
CRN Portfolio Studies
- Genetics of age-related hearing loss
- ElaTion trial
- EFC14146 SINUS-24 nasal polyps study
National and International Collaborators
Guys & St Thomas’ Hospital NHS Foundation Trust
Prof Claire Hopkins
Prof Anne Schilder
Prof Valerie Lund
Prof Steve Morris
Dr Helen Blackshaw
Miss Aneeka Degun
Prof Anne Schilder
Dr Spiros Denaxas
Dr John Robert Hurst
Mr Bhik Kotecha
University of Southampton
Prof Paul Little
Prof Mike Thomas
Dr Caroline Eyles
University of Oxford
Prof Jonathan Cook
Prof David Beard
University of British Columbia
Prof Amin Javer
University of Dresden
Prof Thomas Hummel
Royal Brompton & Harefield NHS Foundation Trust
Prof Stephen Durham
John Radcliffe Hospital, Oxford
Mr Robert Almeyda
Queen Elizabeth Hospital, Birmingham
Mr Shahzada Ahmed
Freeman Hospital, Newcastle
Mr Sean Carrie
Royal National Throat, Nose & Ear Hospital, London
Dr Harsha Kariyawasam
Charing Cross Hospital, London
Mr Hesham Saleh
Queens Medical Centre, Nottingham
Prof Anshul Sama
Royal Surrey County Hospital, Guildford
Mr Sankalp Sunkaraneni
Ninewells Hospital, Dundee
Mr Paul White
University Hospital, Southampton
Mr Rabi Salib
Mr Jim Boardman
LSHTM and MRC Clinical Trials Unit, London
Prof James Carpenter
Farr Institute of Health Informatics Research, London
Prof Andrew Hayward
Radboud University Medical Centre, NL
Prof Maroeska Rovers
Ms Machteld M.H.T. van Egmond
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INTEGRATE, The UK ENT Trainee Research Collaborative. Admission avoidance in tonsillitis and peritonsillar abscess: A prospective national audit during the initial peak of the COVID‐19 pandemic. Clinical Otolaryngology. 2021 Mar;46(2):363-372. https://doi.org/10.1111/coa.13680
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Liu DT, Sabha M, Damm M, Philpott C, Oleszkiewicz A, Hähner A et al. Parosmia is associated with relevant olfactory recovery after olfactory training in postinfectious smell loss. The Laryngoscope. 2021 Mar;131(3):618-623. https://doi.org/10.1002/lary.29277
Huart C, Philpott C, Altundag A, Fjaelstad AW, Frasnelli J, Gane S et al. Systemic corticosteroids in COVID-19 related smell dysfunction: an international view. International Forum of Allergy & Rhinology . 2021 Feb 3.
Maspero JF, Philpott C, Hellings PW, Hopkins C, Wagenmann M, Siddiqui S et al. Health-Related Quality of Life Impairment Among Patients With Severe Chronic Rhinosinusitis With Nasal Polyps in the SINUS-24 Trial. 2021. Abstract from 2021 AAAAI, . https://doi.org/10.1016/j.jaci.2020.12.485
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Hardman JC, Philpott C. Admission avoidance in acute epistaxis: a prospective national audit during the initial peak of the COVID‐19 pandemic. Clinical Otolaryngology. 2021 Jan 16. https://doi.org/10.1111/coa.13716
Addison AB, Wong B, Ahmed T, Macchi A, Konstantinidis I, Huart C et al. Clinical Olfactory Working Group Consensus Statement on the Treatment of Post Infectious Olfactory Dysfunction. Journal of Allergy and Clinical Immunology. 2021 Jan 13. https://doi.org/10.1016/j.jaci.2020.12.641
McDermott C, Vennik J, Philpott C, Le Conte S, Thomas M, Eyles C et al. Maximising recruitment to a randomised controlled trial for chronic rhinosinusitis using qualitative research methods: the MACRO conversation study. Trials. 2021 Jan 13;22(1). 54. https://doi.org/10.1186/s13063-020-04993-w
Hong Ta N, Gao J, Philpott C. A systematic review to examine the relationship between objective and patient-reported outcome measures in sinonasal disorders: recommendations for use in research and clinical practice. International Forum of Allergy & Rhinology . 2021 Jan 8. https://doi.org/10.1002/alr.22744
Hopkins C, Alanin M, Philpott C, Harries P, Whitcroft K, Qureishi A et al. Management of new onset loss of sense of smell during the COVID-19 pandemic - BRS Consensus Guidelines. Clinical Otolaryngology. 2021 Jan;46(1):16-22. https://doi.org/10.1111/coa.13636
Fokkens WJ, Mullol J, Kennedy DW, Philpott C, Seccia V, Kern R et al. Mepolizumab reduces the need for surgery in patients with chronic rhinosinusitis with nasal polyps. 2021.
GCCR Group Author . Recent smell loss is the best predictor of COVID-19 among individuals with recent respiratory symptoms. Chemical Senses. 2021;46. bjaa081. https://doi.org/10.1093/chemse/bjaa081
Keltie K, Donne A, Daniel M, Stephenson K, Wyatt M, Kuo M et al. Paediatric tonsillectomy in england a cohort study of clinical practice and outcomes using Hospital Episode Statistics data (2008‐2019). Clinical Otolaryngology. 2020 Dec 29. https://doi.org/10.1111/coa.13707
GCCR Group Author . Recent smell loss is the best predictor of COVID-19: a preregistered, cross-sectional study. Chemical Senses. 2020 Dec 25. https://doi.org/10.1101/2020.07.22.20157263
Huart C, Philpott C, Konstantinidis I, Altundag A, Trecca EMC, Cassano M et al. Comparison of COVID-19 and common cold chemosensory dysfunction. Rhinology. 2020 Dec 1;58(6):623-625. https://doi.org/10.4193/Rhin20.251
Orlandi R, Kingdom TT, Smith TL, Bleier B, DeConde A, Luong A et al. International Consensus Statement on Rhinology and Allergy: Rhinosinusitis. International Forum of Allergy & Rhinology . 2020 Nov 24. https://doi.org/10.1002/alr.22741
Rocke J, Hopkins C, Philpott C, Kumar N. Is loss of sense of smell a diagnostic marker in COVID-19: A Systematic Review and Meta-analysis. Clinical Otolaryngology. 2020 Nov 1;45(6):914-922. https://doi.org/10.1111/coa.13620
Amin N, Walker A, Alobid I, Anari S, Bast F, Bhalla RK et al. Defining appropriateness criteria for endoscopic sinus surgery in the management of adult dental implant patients with incidental maxillary sinus findings on conebeam computed tomography. Clinical Otolaryngology. 2020 Nov;45(6):862-869. https://doi.org/10.1111/coa.13609
Philpott C. Many UK healthcare workers may have had coronavirus without knowing it. 2020.
Lin Z, Philpott C, Sisson K, Hemmant B. Lacrimal sac primary squamous cell carcinoma with synchronous tonsillar primary squamous cell carcinoma. Orbit. 2020 Sep 2;39(5):374-378. https://doi.org/10.1080/01676830.2019.1691606
GCCR Group Author . More than smell - COVID-19 is associated with severe impairment of smell, taste, and chemesthesis. Chemical Senses. 2020 Sep;45(7):609–622. https://doi.org/10.1093/chemse/bjaa041
Lechner M, Patel ZM, Philpott C, Lund VJ. Olfactory Loss of Function as a Possible Symptom of COVID-19. JAMA Otolaryngology. 2020 Sep;146(9):872-873. https://doi.org/10.1001/jamaoto.2020.1589
Hopkins C, Alanin M, Philpott C, Harries P, Whitcroft K, Qureishi A et al. Management of new onset anosmia during the COVID pandemic -BRS Consensus Guidelines. Clinical Otolaryngology. 2020 Aug 17.
Lechner M, Chandrasekharan D, Jumani K, Liu J, Gane S, Lund VJ et al. Anosmia as a presenting symptom of SARS-CoV-2 infection in healthcare workers – A systematic review of the literature, case series, and recommendations for clinical assessment and management. Rhinology. 2020 Aug 1;58(4):394-399. https://doi.org/10.4193/Rhin20.189
Lechner M, Counsell N, Liu J, Eynon-Lewis N, Paun S, Lund VJ et al. Anosmia and hyposmia in health-care workers with undiagnosed SARS-CoV-2 infection. The Lancet Microbe. 2020 Aug;1(4). e150. https://doi.org/10.1016/S2666-5247(20)30096-3
Collins R, Hong Ta N, Jennings BA, Prinsley P, Philpott CM, Steel N et al. Cholesteatoma and family history: An international survey. Clinical Otolaryngology. 2020 Jul;45(4):500-505. https://doi.org/10.1111/coa.13544
Ball SG, Boak D, Dixon J, Carrie S, Philpott C. Barriers to accessing healthcare in patients with olfactory and gustatory disorders. Authorea. 2020 Jun 22. https://doi.org/10.22541/au.159285606.60833639
Hopkins C, Alanin M, Philpott C, Harries P, Whitcroft K, Qureishi A et al. Management of new onset anosmia during the COVID pandemic - BRS Consensus Guidelines. 2020. https://doi.org/10.22541/au.159015263.38072348
Parker J, Philpott C, Wyatt T. Sudden loss of smell – why it is a reason to self-isolate. The Conversation. 2020 May 18.
Liu D, Sabha M, Damm M, Philpott C, Oleszkiewicz A, Haehner A et al. Parosmia is associated with relevant olfactory recovery after olfactory training. 2020. https://doi.org/10.22541/au.158938596.67608241
Philpott C. The Impact of Patients Losing Their Sense of Smell. British Journal of Hospital Medicine. 2020 May 4;81(5). 0090. https://doi.org/10.12968/hmed.2020.0090
Wahid NW, Smith R, Clark A, Salam M, Philpott C. The Socioeconomic Cost of Chronic Rhinosinusitis Study. Rhinology. 2020 Apr 1;58(2):112-125. https://doi.org/10.4193/Rhin19.424
Philpott C. Coronavirus: loss of smell and taste reported as early symptoms of COVID-19. The Conversation. 2020 Mar 27.