Studying the effect of air pollutants on health
| ISRCTN | ISRCTN85634746 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN85634746 |
| ClinicalTrials.gov (NCT) | Nil known |
| Clinical Trials Information System (CTIS) | Nil known |
| Integrated Research Application System (IRAS) | 314890 |
| Protocol serial number | IRAS 314890, CPMS 54794 |
| Sponsor | University of Manchester |
| Funder | UK Research and Innovation |
- Submission date
- 10/02/2023
- Registration date
- 20/03/2023
- Last edited
- 04/12/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Ongoing
- Condition category
- Other
Plain English summary of protocol
Background and study aims
Outdoor and indoor pollutants have been linked to a variety of adverse health effects including increasing the risk of heart disease and lung diseases. It is thought that air pollution may also cause problems with memory and the brain's ability to process information. This study is investigating the effect of common air pollutants on brain function in healthy human participants who have family members with brain disorders such as dementia.
Who can participate?
Healthy volunteers aged 50 years or over who have a close family relative with dementia
What does the study involve?
Participants are exposed to a controlled concentration of pollutants (diesel fumes, wood smoke, cleaning products, such as diesel and wood smoke) and the researchers measure their ability to complete a variety of tasks that assess their cognition. Blood samples, nasal washouts and breathing tests will also be collected to look at the effects of pollutant exposures on the immune system.
What are the possible benefits and risks of participating?
There are no direct benefits to taking part in this study. Indirect benefits include the further advancement of the understanding of how pollution exposures affect us all. This is a relatively safe study. The main risk will be exposure to pollutants. Some studies have shown that pollution exposure can be associated with cardiovascular conditions. However, the levels of pollutants used in this study are all within the same levels that we are exposed to in normal day-to-day life. As part of the safety mechanisms of the study, a breathing test will be performed and medical history will be checked to ensure that anyone who is at an increased risk of a side effect from pollutant exposure will be NOT included in the study. The team will also be continuously monitoring the levels of the pollutants during the exposure.
Where is the study run from?
The University of Manchester and the NIHR Clinical Research Facility based at Manchester University Foundation NHS Trust (UK)
When is the study starting and how long is it expected to run for?
September 2022 to December 2025
Who is funding the study?
UK Research and Innovation (UK)
Who is the main contact?
Prof Jacky Smith, jacky.smith@manchester.ac.uk (UK)
Contact information
Principal investigator
2nd Floor Education and Research Centre
Wythenshawe Hospital
Southmoor Road
Manchester
M23 9LT
United Kingdom
 ORCID ID |
0000-0001-8837-4928 |
|---|---|
| Phone | +44 (0)161 291 5863 |
| jacky.smith@manchester.ac.uk |
Scientific
Level 2 Education and Research Centre
Wythenshawe Hospital
Southmoor road
Manchester
M23 9LT
United Kingdom
| ORCID ID |
0000-0002-6134-4347 |
|---|---|
| Phone | +44 (0)7968629781 |
| huda.badri@postgrad.manchester.ac.uk |
Public
Level 2 Education and Research Centre
Wythenshawe Hospital
Southmoor road
Manchester
M23 9LT
United Kingdom
| Phone | +44 (0)7968629781 |
|---|---|
| huda.badri@postgrad.manchester.ac.uk |
Study information
| Primary study design | Observational |
|---|---|
| Study design | Single-centre observational cohort study |
| Secondary study design | Cohort study |
| Participant information sheet | 43199_PIS_v1.5_16Jan2023.pdf |
| Scientific title | Hazard identification platform to assess the health impacts of indoor and outdoor air pollution exposures, through mechanistic toxicology (HIPTOX) |
| Study acronym | HIPTOX |
| Study objectives | Currently, there are two hypotheses as to how air pollution might manifest its acute and chronic impacts on the brain. The first is by direct interaction of inhaled particles, or desorbed chemical constituents, with non-neuronal glial cells and neurons in the brain, based either on their uptake via translocation along olfactory neurons to the olfactory bulb; or their entry across the blood-brain barrier from the circulation. This has been the dominant hypothesis within the field, supported by evidence of combustion-like nanoparticles in the brains of sentinel animals and humans from polluted environments, associated in autopsy samples with histopathological features of early dementia, microglia immune defence activation and neuronal injury. The second hypothesis proposes that the neurological damage reflects an indirect impact of air pollution induced systemic inflammation and its transmission to the brain across the glial-neurovascular unit. Support for this assertion comes from toxicological studies that have shown similar neurological impacts, attributed to particulate challenges, following experimental exposures of animals to the pollutant gas ozone, which cannot access the brain, due to its high reactivity with antioxidants and macromolecules at the air-lung interface. The neurological impacts observed may arise from the release of secondary mediators from the lung and their capacity to induce systemic inflammation and oxidative stress. The indirect action therefore implies a lung-to-brain axis, mediated through the vasculature. This study will investigate the acute and chronic impacts and the likely axis to neuroinflammation induction, through: (A) human challenges to defined source-specific pollutant aerosols using acute physiological readouts through changes in cognitive domains and the detection of peripheral markers of neuroinflammation and neuronal injury |
| Ethics approval(s) | 1. Approved 04/10/2022, the University of Manchester Research Ethics Committee (Research Governance, Ethics and Integrity, 2nd-floor Chrsitie Building, The University of Manchester, Oxford Road, Manchester, M13 9PL, UK; telephone not available; research.ethics@manchester.ac.uk), ref: 2022-14762-25491 2. Approved 06/12/2022, HRA and Health and Care Research Wales (HCRW) (Castlebridge 4, 15-19 Cowbridge Road East, Cardiff, CF11 9AB, UK; +44 (0)1686 252101, (0)2920 230457, (0)7920 565664; approvals@hra.nhs.uk), ref: 22/HRA/4925 |
| Health condition(s) or problem(s) studied | This is a study of healthy volunteers aged 50 years or above who have a close relative with dementia |
| Intervention | Healthy volunteers will be recruited and will undergo cognitive testing, spirometry, blood tests for biomarkers, and nasal lavage and will then undergo controlled pollutant exposures: 1. Diesel 2. Clean air (control) 3. Wood smoke 4. Secondary organic aerosol 5. Cooking emissions 6. Clean air with nitrogen oxides (NOx) 7. Wood smoke with NOx They will then undergo all the pre-exposure measures. Evidence of impairment in cognitive function post-exposure measured using any of these cognitive tasks compared to clean air on each visit both at baseline (pre-pollutant exposure) and 3.5 hours post-exposure: 1. Socio-emotional cognitive functioning is measured by Approach bias using the Expression Recognition Task. The team expects a change in approach bias between pre- and post-pollutant exposure measures compared to pre- and post-clean air exposure. 2. Executive cognitive functioning measured by ‘Cognitive Control’ using the Face Identification Task. The team expects a change in cognitive control between pre- and post-pollutant exposure measures compared to pre- and post-clean air exposure. 3. Working memory ability is measured using the Spatial n-back task. The team expects a change in discrimination ability between pre- and post-pollutant exposure measures compared to pre- and post-clean air exposure. 1. Change in any of these cognitive tasks post pollutant exposure compared to clean air: 1.1. Sustained Attention measured by ‘Long Response Time (RT)’ and Psychomotor Speed measured by ‘Short Response Time (RT)’. Both these metrics are measured using the Psychomotor Vigilance Task on each visit both at baseline (pre-pollutant exposure) and 3.5 hours post-exposure. The team might expect a change in sustained attention between pre- and post-pollutant exposure measures compared to pre- and post-clean air exposure. However, changes in Psychomotor Speed are not anticipated. 1.2. Coarse and fine motor movements are measured using the Pegboard Test on each visit both at baseline (pre-pollutant exposure) and 3.5 hours post-exposure. The team might expect a change in both coarse and fine motor movement between pre- and post-pollutant exposure measures compared to pre- and post-clean air exposure. 2. Change in lung function post-exposure to pollutants compared to clean air measured using spirometry 3. Change in the DNA post pollutant exposure compared to clean air measured using blood tests for biomarkers |
| Intervention type | Other |
| Primary outcome measure(s) |
Evidence of impairment in cognitive function post-exposure measured using any of these cognitive tasks compared to clean air on each visit both at baseline (pre-pollutant exposure) and 3.5 hours post-exposure: |
| Key secondary outcome measure(s) |
1. Change in any of these cognitive tasks post pollutant exposures compared to clean air on each visit both at baseline (pre-pollutant exposure) and 3.5 hours post-exposure: |
| Completion date | 31/12/2025 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Adult |
| Lower age limit | 50 Years |
| Sex | All |
| Target sample size at registration | 45 |
| Key inclusion criteria | 1. Aged ≥50 years old 2. Family history of dementia 3. Provision of signed, written and dated informed consent, prior to any study-specific procedures |
| Key exclusion criteria | 1. Neurological or psychiatric disorder 2. General Practitioner Assessment of Cognition Score of ≤7 3. Current smoker (including e-cigarettes) or ex-smoker of less than 6 months abstinence, and >20 pack-year history 4. Current pregnancy 5. Significantly abnormal spirometry 6. History of cardiac disease 7. History of chronic respiratory or airways disease 8. History of inflammatory diseases (e.g. rheumatoid arthritis, chronic periodontitis, inflammatory bowel disease) 9. History of neurological or psychiatric disorders 10. History of organ transplant 11. Consumption of >3 units of alcohol in the 24 hours preceding the testing visit 12. Any vaccination in the week prior to the testing visit 13. Cold or flu in the 48 hours prior to the testing visit 14. Visual impairment not correctable with glasses/contact lenses. 15. Significant claustrophobia preventing the participant from wearing a mask over the nose and mouth for an hour 16. Concomitant medication use of neurologically active drugs such as opiates/benzodiazepines/anti-epileptics etc 17. Substance misuse |
| Date of first enrolment | 13/12/2022 |
| Date of final enrolment | 30/11/2023 |
Locations
Countries of recruitment
- United Kingdom
- England
Study participating centre
Grafton St
Manchester
M13 9WL
United Kingdom
Results and Publications
| Individual participant data (IPD) Intention to share | Yes |
|---|---|
| IPD sharing plan summary | Stored in non-publicly available repository |
| IPD sharing plan | The dataset generated and analysed will be stored in a non-publicly available repository: the University of Manchester RedCAP database. • The type of data stored: Participant contact details, participant GP contact details, participant demographics (including date of birth, height, weight and ethnicity), participant medical history and current medications for eligibility. Measurements will include clinical measures such as lung function test results (continuous data), and cognitive test results measured in (ms) Data collected in this study will be quantitative data, with repeat measures within individuals. Blood samples will be collected for immune cell analysis and DNA analysis. Fluid samples will be collected from the nasal wash/lavage, to look at inflammatory markers. • The process for requesting access (if non-publicly available): Not publically available. Anonymised summary study data will be shared as part of the publication of the results of the study. • Dates of availability: After the study is completed and published. • Whether consent from participants was required and obtained: Fully informed consent was obtained. • Comments on data anonymization: All subjects will be allocated a pseudonymised ID number and data collected during visits will be analysed under this number. • Any ethical or legal restrictions: Personally identifiable is held securely and will not be available to secondary parties. Data remains the property of the University of Manchester. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | 29/02/2024 | 04/12/2024 | Yes | No | |
| Participant information sheet | version 1.5 | 16/01/2023 | 20/03/2023 | No | Yes |
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
| Study website | Study website | 11/11/2025 | 11/11/2025 | No | Yes |
Additional files
- 43199_PIS_v1.5_16Jan2023.pdf
- Participant information sheet
Editorial Notes
04/12/2024: Publication reference added.
03/04/2023: Internal review.
20/03/2023: Trial's existence confirmed by the HRA and Health and Care Research Wales (HCRW) (UK).
