Plain English Summary
Background and study aims
Hyposmia is a relatively common condition where a person has a reduced sense of smell. Previous studies have shown that a chemical called sodium citrate can improves hyposmia by decreasing mucus calcium levels in the nose. The theory behind these effects relates to calcium ions (positively charged calcium atoms) and their role on olfactory receptor neurons (nerve cells in the nose that detect smell). A reduction in free calcium ions (Ca2+) is likely to make these olfactory neurons more active and therefore improve the sense of smell. The aim of this study is to find out whether spraying a sodium citrate solution into the nose of people with hyposmia is able to improve that person’s sense of smell.
Who can participate?
People with a reduced sense of smell (hyposmia)
What does the study involve?
At the start of the study, all participants complete a number of questionnaires and provide information about themselves. They then undertake a series of smell tests using increasing concentrations of four odours in 250ml bottles. Participants are then randomly allocated to one of two groups. Those in the first group use a nose spray containing sodium citrate (9% concentration) and those in the second group use a nose spray with sterile water. Participants then redo the smell tests with the different odour bottles every 15 minutes for two hours.
What are the possible benefits and risks of participating?
It is expected that some patients may benefit from a temporary improvement in their sense of smell after using the citrate spray. Risks of participating are small. The process of spraying the nose should be neither unpleasant nor painful, but some patients may find they want to sneeze. They may also experience some irritation after application of the spray.
Where is the study run from?
1. James Paget University Hospital (UK)
2. Ipswich Hospital (UK)
When is the study starting and how long is it expected to run for?
January 2015 to June 2016
Who is funding the study?
James Paget University Hospital (UK)
Who is the main contact?
Mr Carl Philpott
C.Philpott@uea.ac.uk
Trial website
Contact information
Type
Scientific
Primary contact
Mr Carl Philpott
ORCID ID
http://orcid.org/0000-0002-1125-3236
Contact details
Norwich Medical School
University of East Anglia
Norwich
NR4 7TJ
United Kingdom
+44 1603 591105
C.Philpott@uea.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N0274185293
Study information
Scientific title
A double-blinded randomised controlled trial of the effects of sodium citrate on olfactory thresholds
Acronym
Study hypothesis
Does the application of sodium citrate to the nose improve the ability to smell of patients with a poor sense of smell when compared with a placebo?
Ethics approval
Added September 2008: Eastern Reseach Ethics Committee (UK), 15/06/2006, ref: 06/MRE05/16
Study design
Randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Ear, Nose and Throat: Smell ability
Intervention
Current interventions as of 19/02/2013:
The study will be undertaken at the ENT department of the Leicester Royal Infirmary and in a research laboratory at the University of Leicester and also in the ENT department at the James Paget University Hospital. Fifty subjects will be recruited. Subjects will be invited to undergo a series of smell tests using graded concentrations of 4 odours in 120ml bottles (1). This test has been described and validated by our previous work (2). The test will be fully explained to the subject beforehand by the researcher who will test the patient. The subject will be started with the smallest concentration of each odour and will ascend through the bottles until they detect 2 in a row, at which point the weaker concentration of the odour will be taken as their threshold. They will have a threshold levels determined for the odours phenethyl alcohol (roses), 1-butanol (pear-like), acetic acid (vinegar) and eucalyptol (menthol).
Then, the subject will then have either 1cm3 sodium citrate 9% or sterile water (half per nostril) sprayed into the nose. Patients will be randomly allocated to one of the two groups using a coded bottle system controlled by the pharmacies at both sites. Both patient and tester will be blinded to the solution used as these will be made in the pharmacy and coded for anonymity - the code will be broken at the end of the trial. Subjects will then be retested with the bottles and threshold levels will be observed for the four odours at 15 minute intervals over 2 hours. The purpose of the repeated tests is to determine the length of the effect (if present) of the citrate on the olfactory ability of the patients (NB: sodium citrate is a licensed product for use in body cavities (e.g. stomach, bladder) and can be found in the British National Formulary - the concentrations proposed do not exceed those used elsewhere).
Previous interventions until 19/02/2013:
The study will be undertaken at the ENT department of the Leicester Royal Infirmary and in a research laboratory at the University of Leicester and also in the ENT department at the West Suffolk Hospital. One hundred subjects will be recruited. Subjects will be invited to undergo a series of smell tests using graded concentrations of 4 odours in 120ml bottles (1). This test has been described and validated by our previous work (2). The test will be fully explained to the subject beforehand by the researcher who will test the patient. The subject will be started with the smallest concentration of each odour and will ascend through the bottles until they detect 2 in a row, at which point the weaker concentration of the odour will be taken as their threshold. They will have a threshold levels determined for the odours phenethyl alcohol (roses), mercaptan (gas), acetic acid (vinegar) and eucalyptol (menthol).
Then, the subject will undergo a sodium citrate nasal douche at a specific concentration or will douche with sterile water. There will be three concentrations used (3%, 6% and 9%) and a control solution (sterile water). Patients will be randomly allocated to one of the four groups using a coded bottle system. Both patient and tester will be blinded to the solution used as these will be made in the pharmacy and coded for anonymity - the code will be broken at the end of the trial. Subjects will then be retested with the bottles and threshold levels will be observed for the four odours at 15 minute intervals over 2 hours. The purpose of the repeated tests is to determine the length of the effect (if present) of the citrate on the olfactory ability of the patients (NB: sodium citrate is a licensed product for use in body cavities (e.g. stomach, bladder) and can be found in the British National Formulary - the concentrations proposed do not exceed those used elsewhere).
Intervention type
Drug
Phase
Not Specified
Drug names
Sodium Citrate
Primary outcome measure
Primary outcome measure as 29/07/2016:
Olfactory threshold for PEA odour is measured using a psychophysical test (two-alternative forced choice ascending ladder technique) at baseline and 15 minute intervals up to 2 hours maximum.
Original primary outcome measure:
An improvement in their sense of smell and their general well-being.
Secondary outcome measures
Secondary outcome measure as of 29/07/2016:
Olfactory thresholds for ACA, EUC and BUT odours are measured using a psychophysical test (two-alternative forced choice ascending ladder technique) at baseline and 15 minute intervals up to 2 hours maximum.
Secondary outcome measures added as of 19/02/2013:
A subjective improvement in their sense of smell and their general well-being
Overall trial start date
01/01/2015
Overall trial end date
30/06/2016
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
All patients with an objective reduction in their ability to smell.
Participant type
Patient
Age group
All
Gender
Both
Target number of participants
100
Participant exclusion criteria
Current inclusion criteria as of 19/02/2013:
1. Patients who are proven to have a normal sense of smell
2. Patients with nasal polyps or other sinonasal disease
Previous inclusion criteria until 19/02/2013:
1. Patients who are proven to have a normal sense of smell
2. Patients with nasal polyps
Recruitment start date
11/08/2008
Recruitment end date
01/08/2009
Locations
Countries of recruitment
United Kingdom
Trial participating centre
James Paget University Hospital
Lowestoft Road
Gorleston-on-Sea
Great Yarmouth
Norfolk
NR31 6LA
United Kingdom
Trial participating centre
Ipswich Hospital
Heath Road
Ipswich
IP4 5PD
United Kingdom
Sponsor information
Organisation
University Hospitals of Leicester NHS Trust (UK)
Sponsor details
University Hospitals of Leicester NHS Trust Headquarters
Level 3
Balmoral Building
Leicester Royal Infirmary
Infirmary Square
Leicester
LE1 5WW
United Kingdom
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Hospital/treatment centre
Funder name
James Paget University Hospital
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Planned publication in Rhinology journal.
Intention to publish date
31/12/2016
Participant level data
Available on request
Basic results (scientific)
Publication list
2017 results in https://www.ncbi.nlm.nih.gov/pubmed/28339165